Jan 22

Posted by Dr Colin Holloway

Menopause. 2016 Nov 21. [Epub ahead of print]

Is vulvovaginal atrophy due to a lack of both estrogens and androgens?

Labrie F¹, Martel C, Pelletier G.

Author information

• ¹1Laval University, Quebec City, Quebec, Canada 2Endoceutics Inc, Quebec City, Quebec, Canada.

Abstract

OBJECTIVE:

The aim of this study was to review the preclinical data showing the role of both estrogens and androgens in the physiology of the vagina, and, most likely, in vulvovaginal atrophy of menopause.

METHODS:

Mass spectrometry-based assays (validated according to the FDA guidelines) for the measurement of sex steroids, their precursors, and metabolites were used. In addition to fixation of the vagina for morphological examination, histomorphometry, immunocytochemistry, immunofluorescence, and quantitative reverse transcription polymerase chain reaction were performed.

RESULTS:

The vaginal epithelium of the animals receiving dehydroepiandrosterone (DHEA) was made of large multilayered columnar mucous cells showing distended cytoplasmic vacuoles representative of an androgenic effect. DHEA also stimulates collagen fiber compactness of the lamina propria (second layer)-an effect essentially due to an androgenic effect, whereas stimulation by DHEA of the muscularis in the third vaginal layer is approximately 70% due to the androgenic conversion of DHEA. Stimulation of the surface area of the nerve endings, on the contrary, is exclusively androgenic. Vaginal weight stimulation by DHEA is about 50% androgenic and 50% estrogenic.

CONCLUSIONS:

Practically all studies on the influence of steroid hormones in the vagina have focused on luminal epithelial cells. Since all estrogens and androgens in postmenopausal women are made intracellularly and derive from the conversion of circulating DHEA, it is of interest to observe from these preclinical data that DHEA exerts both estrogenic and androgenic activity in the three layers of the vagina, the stimulatory effect on nerve density being 100% androgenic. Taking vaginal weight as a global parameter, the stimulatory effect of DHEA in the rat vagina is about equally estrogenic and androgenic, thus illustrating the importance of androgens in vaginal morphology and function, and the likely importance of androgens in vulvovaginal atrophy of menopause.

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Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

Oct 15

Posted by Dr Colin HollowayVaginal dryness (atrophy) is common in the menopause, and is due to lack of Oestrogen. See my blog of Feb 17 – Vaginal problems.  For those who do not want oestrogen, or cannot take it for any reason, Oxytocin is a useful alternative. Oxytocin is known as the comfort hormone as it makes us feel warm and cuddly. (nursing mothers make lots of it)

Vaginal Problems

Feb 17

Post Reprod Health. 2015 May 19. pii: 2053369115577328. [Epub ahead of print]

Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

Al-Saqi SH¹, Uvnäs-Moberg K², Jonasson AF³.

Author information

Abstract

OBJECTIVE:

To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy.

DESIGN:

Double-blinded randomised controlled trial.

SETTING:

Healthy post-menopausal women in Stockholm, Sweden.

PARTICIPANTS:

Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden.

MAIN OUTCOME MEASURES:

The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation.

RESULTS:

The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089).

CONCLUSIONS:

Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy.

© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

KEYWORDS:

Estrogen; oxytocin; post-menopausal; vaginal atrophy; vagitocin

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DHEA for Urogenital Atrophy and Sexual Function

Jan 28

Posted by Dr Colin Holloway

DHEA for Urogenital Atrophy and Sexual Function

Susan R. Davis, MBBS, FRACP, PhD

Disclosures

January 15, 2015

Question

What is the current evidence on the use of intravaginal dehydroepiandrosterone (DHEA) in urogenital atrophy and sexual function?

Commentary from Susan R. Davis, MBBS, FRACP, PhD

Sex steroids are vital for the integrity of the urogenital tract (vagina, vulva, lower urinary tract, and supporting pelvic structures). These tissues are rich in estrogen and androgen receptors.^[1] In addition, estrogen and testosterone enhance blood flow to the genital tract,^[2] which is fundamental for genital sexual arousal and lubrication.^[3]

;The fall in estrogen at menopause and the gradual decline in androgen levels with age^[4] result in what is now described as genitourinary syndrome of menopause (GSM). This includes vulvovaginal atrophy (VVA) and an increase in vaginal pH.^[3] At a cellular level, there is a reduction in healthy vaginal epithelial superficial cells and an increase in parabasal cells. The increase in vaginal pH changes the vaginal microflora. Lactobacilli disappear, and as a consequence there is increased vulnerability to vaginal infection. Symptoms of VVA include vaginal dryness, irritation, itching, infection, and dyspareunia.^[5] This in turn leads to diminished sexual desire, arousal difficulties, diminished physical and emotional sexual satisfaction, and relationship issues.^[6]

Most postmenopausal women will experience some GSM symptoms.^[7] Symptoms of VVA can be effectively treated with either vaginal or systemic estrogen therapy.^[8] Estrogenization will thicken and revascularize the vaginal epithelium, lower vaginal pH, and normalize vaginal flora. The number of vaginal epithelial superficial cells will increase.^[8,9] Although data show that vaginal estrogen acts locally, thus minimizing systemic exposure to estrogen, some studies have shown blood estradiol levels increase with vaginal application.^[10,11,12] A two- to fivefold increase in serum estradiol has been reported after one week of vaginal administration of a 25 µg estradiol vaginal tablet or 1g of 0.625 mg conjugated estrogen cream.^[10] After 24 weeks of treatment, only 2% of women have estradiol levels outside the postmenopausal range.^[13]

Researchers have looked for alternative approaches for GSM management. In postmenopausal women, adrenal dehydro-epiandrosterone (DHEA) is an important precursor for extra-gonadal biosynthesis of estrone (by aromatization) and testosterone (by 5-alpha reduction). Casson and colleagues first studied the effects of a vaginal DHEA 150 mg pessary versus placebo in five premenopausal women as a mode of hormone delivery and reported an increase in blood levels of DHEA with this approach.^[14] The daily vaginal application of three different doses of DHEA cream (6.5 mg, 13 mg, and 23.5 mg) was studied for one week in postmenopausal women.^[15] Labrie and colleagues reported a decrease in vaginal pH, an improvement in the vaginal cell maturation index, and restoration of DHEA levels to the range for premenopausal women at the highest dose.^[15] The circulating levels of other sex steroids remained within the normal range for postmenopausal women.

A randomized controlled trial of the daily application of three different doses of vaginal DHEA ovules (3.25 mg, 6.5 mg, or 13 mg) was studied over 12 weeks in 218 postmenopausal women who met the entry criterion of dyspareunia. This single study has resulted in a number of publications to support the efficacy of this treatment for VVA.^{[16,17,18,19,20,21]} In these various publications, the investigators have reported an improvement in vaginal cytology and a reduction in pH. An analysis restricted to the women who fulfilled investigational criteria for a low percentage of vaginal epithelial cells and vaginal pH greater than 5 reported an increase in superficial cells and a reduction in pH with an associated improvement in dyspareunia compared with placebo.^[21] Sexual function was assessed by three questions in the Menopause Quality of Life Questionnaire (sexual desire, vaginal dryness during intercourse, or avoiding intimacy) and by the Abbreviated Sexual Function Questionnaire. At 12 weeks the total Menopause Quality of Life Questionnaire sexual domain score showed a significantly greater response for each treatment group versus placebo, with more mixed findings in the Abbreviated Sexual Function Question-naire.^[17]Vitality

DHEA Benefits Include Helping To Relieve Vaginal Pain Caused By Menopausal Dryness, Atrophy

Jan 5, 2016 12:01 AM By Susan Scutti

New research suggests a DHEA vaginal suppository for treating vaginal dryness may be one step closer to government approval. The DHEA formulation could provide an effective alternative for women hoping to ease their symptoms of menopause — without resorting to estrogen.

During perimenopause, vaginal tissues begin to atrophy, the lining thins and secretes less and less fluid, and the pH becomes more alkaline, explain the researchers. Not only do these signs of age lead to discomfort during sex, they also increase a woman’s susceptibility to infections and urinary problems. While hormonal treatments may help alleviate such symptoms, many women have a past history of cancer or higher genetic risk for reproductive cancers rendering such medicines unsafe.

As an alternatives to estrogen treatments, some women resort to non-hormonal lubricants. While these products may temporarily provide moisture and even ease sexual pains, they do not correct the physical problems producing the symptoms. By comparison, DHEA (dehydroepiandrosterone) is a precursor of estrogens and androgens and so can induce physical changes that protect the vagina, according to the researchers. That said, the DHEA product in this study is still considered “hormonal” by regulatory authorities, such as the Food and Drug Administration.

Safety Testing a New Product

For the study, a research team from EndoCeutics, a private bio-pharm company, recruited nearly 500 women to participate in a randomized, double-blind, placebo-controlled trial of its DHEA suppository product. The majority of the women, 84 percent, complained of moderate to severe vaginal dryness. The researchers divided the women, ranging in age from 40 to 80, into two groups: 325 women in the DHEA-treatment group and 157 in a placebo group. After a baseline gynecological test, the women used a daily suppository of either the DHEA or placebo, depending on their group, for 12 weeks.

Compared with the women using a placebo, the women who used the DHEA ovules experienced improvements. Their scores on a scale of 0 to 3 for pain during sex dropped 0.36 points more than the women using placebo and their scores improved by 0.27 points with regard to vaginal dryness. Importantly, the gynecologists who examined them saw 86 percent to 121 percent better improvements in vaginal secretions, integrity of the vaginal lining, lining thickness, and tissue color in the women who used DHEA, while their vaginal pH shifted 0.66 points toward acidity (a positive direction).

“The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6 percent of the participants,” noted the researchers in their study.

Importantly, this therapy has not been tested in patient at risk or with a history of breast cancer.

“Although this medication is considered ‘hormonal,’ the mechanism appears to be primarily local with minimal side effects beyond vaginal discharge from the suppository,” Dr. JoAnn V. Pinkerton, executive director of North American Menopause Society, stated in a press release.

Source: Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016.

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Vaginal oestrogen for overactive bladder in post-menopausal women.

Sep 16

Posted by Dr Colin HollowayBr J Nurs. 2015 Jun 11;24(11):582-5. doi: 10.12968/bjon.2015.24.11.582.

Vaginal oestrogen for overactive bladder in post-menopausal women.

Ostle Z¹.

Author information

Abstract

This article asks the question ‘Should nurses recommend vaginal oestrogen for overactive bladder in post-menopausal women?’ The article will review the evidence for use of vaginal oestrogen and consider the potential side-effects and risks. The main finding is that vaginal oestrogen is effective for treatment of overactive bladder in post-menopausal women with vaginal atrophy. However, vaginal atrophy is undertreated. This article identifies some of the barriers that may prevent diagnosis and treatment, and suggests changes in practice. Nurses should take the initiative and ask post-menopausal women about symptoms. Nurses should be trained to examine women, diagnose vaginal atrophy and discuss treatment.

KEYWORDS:

Continence; Overactive urinary bladder; Postmenopause; Urge urinary incontinence; Vagina

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Vaginal estrogen for genitourinary syndrome of menopause

Jun 10

Posted by Dr Colin Holloway

Vaginal problems are common in menopause, and that includes bladder and urinary symptoms. The fact is that both the bladder and vagina thrive under the influence of oestrogen, and so oestrogen is essential for both vagina and bladder health. Unfortunately, too many women suffer in silence over menopausal vaginal problems and do not discuss it with their doctors.

Vaginal estrogen for genitourinary syndrome of menopause: A systematic review

Obstetrics and Gynecology, 12/05/2014  Evidence Based Medicine  Review Article

Rahn DD, et al. – In this study, authors want to comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy–related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy–related symptoms and in patients at risk for estrogen–related neoplasia.

Methods

• MEDLINE and Cochrane databases were searched from inception to April 2013.
• Authors included randomized controlled trials and prospective comparative studies.
• Interventions and comparators included all commercially available vaginal estrogen products.
• Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.
• Authors double–screened 1,805 s, identifying 44 eligible studies.
• Discrepancies were adjudicated by a third reviewer.
• Studies were individually and collectively assessed for methodologic quality and strength of evidence.

Results

• Studies were extracted for participant, intervention, comparator, and outcomes data, including patient–reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events.
• Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI).
• Urinary tract infection rates decreased.
• The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high–dose conjugated equine estrogen cream.
• Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen.
• Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.

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Vaginal estrogen for genitourinary syndrome of menopause: A systematic review

May 20

Posted by Dr Colin Holloway

Vaginal problems are very common in menopausal women. Most suffer in silence unnecessarily. HRT helps, but sometimes a vaginal cream is needed. It helps the bladder as well, as a bonus. Read the evidence.

Vaginal estrogen for genitourinary syndrome of menopause: A systematic review
Obstetrics and Gynecology, 12/05/2014  Evidence Based Medicine  Review Article

Rahn DD, et al. – In this study, authors want to comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy–related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy–related symptoms and in patients at risk for estrogen–related neoplasia.

Methods

• MEDLINE and Cochrane databases were searched from inception to April 2013.
• Authors included randomized controlled trials and prospective comparative studies.
• Interventions and comparators included all commercially available vaginal estrogen products.
• Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.
• Authors double–screened 1,805 s, identifying 44 eligible studies.
• Discrepancies were adjudicated by a third reviewer.
• Studies were individually and collectively assessed for methodologic quality and strength of evidence.

Results

• Studies were extracted for participant, intervention, comparator, and outcomes data, including patient–reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events.
• Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI).
• Urinary tract infection rates decreased.
• The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high–dose conjugated equine estrogen cream.
• Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen.
• Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.

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Vaginal Health.

Feb 17

Posted by Dr Colin HollowayWe are now realizing that the vagina is an active and very complex organ, just like other organs such as the eye, ear, liver and so on. It tends to be neglected when we discuss good health, and most women suffer vaginal problems silently. Doctors don’t ask, women don’t tell. To have a good quality of  life in the peri- and post menopause, a healthy and properly functioning vagina is important.  Oestrogen is the most important hormone for vaginal health. Climacteric. 2012 Feb;15(1):36-44. doi: 10.3109/13697137.2011.647840. Epub 2011 Dec 14.

Vaginal Health: Insights, Views & Attitudes (VIVA) – results from an international survey.

Nappi RE, Kokot-Kierepa M.

Source

Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause Unit, Department of Obstetrics and Gynecology, IRCCS ‘S Matteo Foundation’, University of Pavia, Pavia, Italy.

Abstract

OBJECTIVE:

To assess knowledge of vaginal atrophy among women using the Vaginal Health: Insights, Views & Attitudes (VIVA) survey.

METHODS:

A structured online questionnaire was used to obtain information from 3520 postmenopausal women aged 55-65 years living in Great Britain, the United States, Canada, Sweden, Denmark, Finland, and Norway.

RESULTS:

In total, 45% of women reported experiencing vaginal symptoms. Only 4% of women attributed these symptoms to vaginal atrophy, and 63% failed to recognize vaginal atrophy as a chronic condition. Overall, 44% of respondents did not have a gynecologist, but this percentage varied between countries. Most women (75%) felt that vaginal atrophy had a negative impact on life, but this perception also showed country-specific differences. Most Finnish respondents (76%) were satisfied with the amount of information available about vaginal atrophy, compared with just 37-42% of women from other countries. Most women used over-the-counter products for vaginal atrophy symptoms, but specific means of treating the underlying cause were less well known. Almost half (46%) of all respondents lacked knowledge about local estrogen therapy, with women in Great Britain, the United States and Canada being most likely to lack knowledge of such treatment. Overall, 30% of women would consider taking local estrogen therapy, with vaginal tablets being the preferred option in all countries.

CONCLUSION:

Postmenopausal women have a low understanding of vaginal atrophy. Medical practitioners should proactively raise this topic, help patients to understand that vaginal atrophy is a chronic condition, and discuss treatment options. Country-specific approaches may be required.

——————————————————————————————————————————————–

Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman’s life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae(ridges, folds) disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial.

AI = aromatase inhibitor; CI = confidence interval; ER = estrogen receptor; HT = hormone therapy; SERM = selective ER modulator; VMI = vaginal maturation index; VVA = vulvovaginal atrophy

Vulvovaginal atrophy (VVA) is a common condition, especially in postmenopausal women. Vaginal atrophy, atrophic vaginitis, and urogenital atrophy are other terms used to describe this constellation of symptoms associated with decreased estrogenization of the vulvovaginal tissue. Although treatment with topical estrogen is effective in alleviating symptoms, women frequently do not report symptoms and thus go untreated.

Common symptoms include vaginal dryness, irritation, postcoital bleeding, and soreness. These symptoms may be associated with vaginal discharge and dyspareunia. Urinary symptoms associated with VVA include frequency, urgency, and urge incontinence.

PREVALENCE

Vulvovaginal atrophy can occur at any time in a woman’s life cycle, although it is more common in the postmenopausal phase, a time of hypoestrogenism. Other causes of a hypoestrogenic state include lactation, various breast cancer treatments, and use of certain medications. In situations other than menopause, VVA may resolve spontaneously when estrogen levels are restored. After menopause, the elasticity of the vagina is reduced and connective tissue increases.A decline in estrogen level causes a decrease in vaginal blood flow and a decrease in vaginal lubrication. These changes can be reversed by the use of estrogens.

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Vaginal Problems

Feb 17

Posted by Dr Colin HollowayMayo Clin Proc. 2010 January; 85(1): 87–94. doi:  10.4065/mcp.2009.0413 PMCID: PMC2800285

Vulvovaginal Atrophy

Maire B. Mac Bride, MBBCh, Deborah J. Rhodes, MD, and Lynne T. Shuster, MD Author information ►Copyright and License information ► This article has been cited by other articles in PMC. Go to:

Abstract

Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman’s life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial.

AI = aromatase inhibitor; CI = confidence interval; ER = estrogen receptor; HT = hormone therapy; SERM = selective ER modulator; VMI = vaginal maturation index; VVA = vulvovaginal atrophy

Vulvovaginal atrophy (VVA) is a common condition, especially in postmenopausal women. Vaginal atrophy, atrophic vaginitis, and urogenital atrophy are other terms used to describe this constellation of symptoms associated with decreased estrogenization of the vulvovaginal tissue. Although treatment with topical estrogen is effective in alleviating symptoms, women frequently do not report symptoms and thus go untreated.^1,2

Common symptoms include vaginal dryness, irritation, postcoital bleeding, and soreness. These symptoms may be associated with vaginal discharge and dyspareunia. Urinary symptoms associated with VVA include frequency, urgency, and urge incontinence.Go to:

PREVALENCE

Vulvovaginal atrophy can occur at any time in a woman’s life cycle, although it is more common in the postmenopausal phase, a time of hypoestrogenism. Other causes of a hypoestrogenic state include lactation, various breast cancer treatments, and use of certain medications. In situations other than menopause, VVA may resolve spontaneously when estrogen levels are restored.

Numerous retrospective studies have evaluated the prevalence of symptoms of VVA (Table 1).^3–10Although these studies differ in type of symptoms elicited, study design, and study population, they provide a range of estimates of VVA prevalence. They all used self-reported symptoms of vaginal dryness to determine the prevalence of VVA. In general, the prevalence ranged from about 4% in the early premenopausal groups to 47% in the late postmenopausal group.

TABLE 1. Studies Assessing Prevalence of Vaginal Dryness

The prevalence of VVA in some subgroups of women can be much higher. In a cohort of breast cancer survivors, vaginal dryness was present in 23.4% of the premenopausal patients and in 61.5% of the postmenopausal patients.⁸Go to:

PHYSIOLOGY

Vulvovaginal atrophy occurs under conditions of hypoestrogenism. In the premenopausal state, estradiol levels fluctuate from 10 to 800 pg/mL (to convert to pmol/L, multiply by 3.671),¹¹ depending on when measured during the cycle. In the postmenopausal state, estradiol levels are typically less than 30 pg/mL. After menopause, circulating estradiol derives from estrone, which is peripherally converted in adipose tissue from adrenal androstenedione.

The vaginal epithelium is a stratified squamous epithelium, which until menopause is moist and thick with rugae. At menopause, with declining levels of estrogen, the vaginal epithelium thins. Fewer epithelial cells result in less exfoliation of cells into the vagina. As epithelial cells exfoliate and die, they release glycogen, which is hydrolyzed to glucose. Glucose, in turn, is broken down into lactic acid by the action of lactobacillus, a normal vaginal commensal organism. Without this cascade, the pH in the vagina rises, resulting in a loss of lactobacilli and an overgrowth of other bacteria, including group B streptococcus, staphylococci, coliforms, and diphtheroids¹² (Figure 1). These bacteria can cause symptomatic vaginal infections and inflammation. After menopause, the elasticity of the vagina is reduced and connective tissue increases.¹³ A decline in estrogen level causes a decrease in vaginal blood flow and a decrease in vaginal lubrication. These changes can be reversed by the use of estrogens.^14,15

FIGURE 1. Proposed cascade-of-effects mechanism for vulvovaginal atrophy.

The effects of endogenous estrogens on vulvovaginal tissues are mediated through estrogen receptors (ERs) α and β, found at sites throughout the urogenital area, including the vagina, vulva, labia, urethra, and bladder trigone. These sites, in turn, regulate transcription at specific areas on the DNA.¹⁶Go to:

SYMPTOMS

The initial symptom is often lack of lubrication during intercourse. Eventually, persistent vaginal dryness may occur. Thinning of the epithelial lining may also cause pruritus, soreness, and a stinging pain in the vaginal and vulvar area, which, in turn, may further contribute to dyspareunia. Vaginal spotting, due to small tears in the vaginal epithelium, may also occur. Women with VVA may report a thin yellow or grey watery discharge secondary to the rise in pH that accompanies VVA.¹⁷

Women with VVA often report symptoms such as urgency, frequency, nocturia, and urge incontinence. Urinalysis may show microscopic hematuria. Recurrent urinary tract infections can also result. Stress incontinence is commonly found in this age group of women, but current evidence suggests it is not directly attributable to VVA.¹⁸

Women do not always report their symptoms of VVA. They are more likely to report vaginal discharge and urinary urgency but are less likely to report vaginal itching, soreness, or dyspareunia. Women may not report symptoms because they are self-treating, feel the symptoms are not important enough, or are embarassed.¹⁹Go to:

CLINICAL FINDINGS

Clinical findings include atrophy of the labia majora and vaginal introitus. The labia minora may recede. Vulvar and vaginal mucosae may appear pale, shiny, and dry; if there is inflammation, they may appear reddened or pale with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. Vaginal shortening and narrowing tend to occur.²⁰

A thin watery yellow vaginal discharge may be observed. A urethral caruncle, a small, soft, smooth friable red outgrowth along the edge of the urethra, may develop.Go to:

CLINICAL TESTS

The diagnosis of VVA is a clinical one. However, 2 tests may be used to support the diagnosis: a vaginal pH and a vaginal maturation index (VMI). To assess pH, a piece of litmus paper is placed on the lateral vaginal wall until moistened. A pH of 4.6 or greater indicates VVA, assuming the patient does not have bacterial vaginosis. Premenopausal women without VVA typically have a pH of 4.5 or less.¹²

The VMI (Figure 2) is the criterion standard for VVA confirmation but is generally not used or needed in clinical practice. This test assesses the relative proportion of parabasal, intermediate, and superficial vaginal epithelial cell types. In premenopausal women, greater than 15% superficial cells would be considered normal; however, in postmenopausal women with VVA, the typical proportion would be less than 5%.

FIGURE 2. Photomicrographs of superficial and intermediate cells (top) and atrophic cells (bottom). (Papanicolaou stain; original magnification x20). Courtesy of the Mayo Cytopathology Laboratory. Go to:

DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes other conditions that cause chronic vaginal and vulvar itching, discharge, or pain (eg, vaginal infections, irritants, and vulvovaginal dermatoses). Vaginal infections can be caused by bacteria, viruses, protozoa, and fungi. The 3 most common vaginal infections are Candidavulvovaginitis, bacterial vaginosis, and trichomoniasis. Bacterial vaginosis may result from atrophic changes in the vagina. Irritants that can cause chronic vaginal itch include perfumes, any locally applied lubricant or moisturizer, and soaps. Vulvovaginal dermatoses, including lichen sclerosus, lichen planus, and lichen simplex chronicus, may cause similar symptoms.²¹ Cancer and precancerous lesions, including vulvar intraepithelial neoplasm, vulvar cancer, and extramammary Paget disease, are in the differential diagnosis of any localized areas of redness, thickening, or ulceration (Table 2). Biopsy should be performed if a malignancy is suspected or if the diagnosis is unclear.

TABLE 2. Differential Diagnosis for Symptoms of Vulvovaginal Atrophy Go to:

TREATMENT

Nonhormonal Treatments

Current over-the-counter treatments include nonhormonal vaginal moisturizers for VVA symptoms and lubricants for dyspareunia. Vaginal moisturizers, which are water based, are available as liquids, gels, or ovules inserted every few days. Vaginal moisturizers can be safely used long term, but they need to be used regularly for optimal effect.

Vaginal lubricants are shorter acting than moisturizers and are applied at the time of sexual activity to reduce dyspareunia. They can be either water or silicone based, with the water-based products being the most widely available. They are applied to the vaginal opening and/or to the penis and often require repeated application during sexual activity. Silicone-based lubricants require application of only a very small amount and last longer; however, they can interfere with erectile function in male partners. The choice of lubricant may depend on individual preferences and product availability.

Hormonal Treatments

On the basis of an evidence-based review of clinical trials examining available low-dose vaginal estrogen preparations for the treatment of VVA in postmenopausal women, The North American Menopause Society (NAMS) 2007 position statement noted that “the choice of therapy should be guided by clinical experience and patient preference.”²² NAMS also stated it is generally unnecessary to prescribe a progestogen in combination with low-dose vaginal estrogen to prevent endometrial hyperplasia or cancer.

On the basis of a meta-analysis of 19 randomized clinical trials involving 4162 postmenopausal women, the 2006 Cochrane Database of Systematic Reviews concluded that vaginal estrogen is an effective treatment for VVA²³ and that all forms, whether cream, ring, or tablet, appeared to relieve symptoms more effectively than nonhormonal gels and placebo. Differences observed between the treatments were in participant preferences.

Therefore, for symptomatic vaginal atrophy that does not respond to self-care measures, estrogen treatment is the standard of care, typically with vaginally administered local estrogens. Prescription vaginal estrogens are available as either estradiol or conjugated estrogens. In some countries outside the United States, vaginal estriol is also available.Go to:

SYSTEMIC ABSORPTION OF VAGINAL HORMONAL PREPARATIONS

An important concern about treatment safety relates to the extent of systemic absorption of vaginal estrogens. The conclusion from several studies comparing different doses of estradiol vaginal tablets^24,25 or different vaginal estrogen preparations (conjugated estrogens and estradiol vaginal tablets)²⁶ is that systemic absorption occurs, but to a limited extent. Labrie et al²⁶ showed that levels of estradiol increased on average from a baseline (pretreatment) level of 3 pg/mL to 17 pg/mL on day 7 of treatment for both estradiol vaginal tablets (25 μg) and conjugated estrogen cream (0.625 mg). Nilsson and Heimer²⁴ showed that, although plasma estradiol concentration diminished by the 14th day of daily treatment with 10 or 25 μg of vaginal estradiol, it was still statistically significantly higher than pretreatment levels. Some evidence shows that estradiol levels diminish over time when vaginal estrogens are used consistently.^24,25

Although vaginal estrogens applied as a cream, vaginal tablets, or a low-dose vaginal ring are systemically absorbed, the rise in serum estrogen levels appears to remain well below premenopausal levels. Nonetheless, this may be of concern to women with a history of breast or other hormonally sensitive cancersGo to:

PRACTICAL ISSUES

Because all low-dose vaginal estrogens appear comparable in efficacy for the treatment of VVA, the choice of estrogen formulation is determined by the clinician and by each woman’s preferences. Estrogen creams are currently the least costly and most widely used but require commitment to regular use for sustained effect. Dosing vaginal creams can be confusing because the dose of active estrogen cream is specified in milligrams, the dose of base cream in grams, and applicator volume in proportions. A simplified approach to dosing is provided in Table 3. The estradiol tablet is preferred by some to avoid the messiness of cream. The estradiol ring is long acting and requires less sustained effort to use; however, it requires dexterity to insert and remove and needs to be replaced every 3 months. The presence of a cystocele or rectocele may cause ring displacement.

TABLE 3. Vaginal Estrogen Products Go to:

SYSTEMIC ESTROGEN AGENTS AND VVA

Systemic estrogen therapy, in the form of patches, oral agents, or a higher-dose vaginal ring, is sometimes used for VVA, especially when the patient also has hot flashes. However, 10% to 20% of women may have residual VVA symptoms even while taking systemic estrogen.²⁷ These women will require administration of local vaginal estrogens alone or along with systemic therapy for relief of VVA symptoms.

Two studies have shown that oral hormone therapy (HT) may worsen symptoms of urinary incontinence. The Heart and Estrogen-Progestin Replacement Study found a higher risk of both urge (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.8; P<.001) and stress incontinence (odds ratio, 1.7; 95% CI, 1.5-2.1; P<.001) in the hormone-treated group vs the placebo group throughout the treatment period.²⁸

It has been suggested that urge incontinence worsened with HT because progesterone was a component. However, in the Women’s Health Initiative, 3 treatment groups were evaluated for urge incontinence (conjugated estrogens alone, conjugated estrogens with progesterone, and placebo). Women given conjugated estrogens alone were at increased risk of developing urge incontinence compared with those receiving placebo (relative risk, 1.32; 95% CI, 1.10-1.58), whereas the women given combination conjugated estrogens with progesterone were not (relative risk, 1.15; 95% CI, 0.99-1.34).²⁹ Thus, whether oral HT adversely affects urge urinary incontinence remains unclear.Go to:

BREAST CANCER AND VVA

Currently, more than 2 million women in the United States have a history of breast cancer. In breast cancer survivors, the estimated prevalence of vaginal atrophy, by symptom report, ranges from 23% to 61%.⁸ Prescribing even very low-dose localized estrogen treatments for these patients can cause concern because of the potential for systemic absorption.

Concern about the provision of any form of estrogen, either systemic or local, to breast cancer survivors contributes to the high incidence of VVA in women with breast cancer. Discontinuation of HT may trigger the onset of VVA symptoms.

Many surgical, endocrine, and chemotherapeutic treatments for breast cancer can cause or exacerbate VVA.^10,30–37 Tamoxifen acts as an estrogen antagonist or agonist depending on the target organ and menopausal status. In premenopausal women, tamoxifen may cause VVA by acting as an estrogen antagonist and blocking the naturally high levels of endogenous estrogen. In postmenopausal women, however, it acts as an estrogen agonist on the urogenital tract.³⁸

Raloxifene does not appear to have an effect on the urogenital area in either premenopausal or postmenopausal women. Davies et al³⁵ found no significant differences in incidence of VVA when comparing databases of postmenopausal women treated with raloxifene vs placebo.

Aromatase inhibitors (AIs) are prescribed as adjuvant systemic therapy to women with ER⁺ breast cancer. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) study, designed to compare outcomes in postmenopausal breast cancer survivors taking tamoxifen, anastrozole (an AI), or a combination of both, Cella et al¹⁰ demonstrated that vaginal dryness was more common in the group taking anastrozole than in the group taking tamoxifen (18.5% vs 9.1%). Dyspareunia was also more common in the anastrozole group (17.3% vs 8.1%).¹⁰

Chemotherapy itself can result in vaginal dryness and dyspareunia. In a randomized clinical trial comparing high-dose chemotherapy with standard-dose chemotherapy for breast cancer survivors, followed by radiotherapy and tamoxifen in all patients, more patients in the high-dose chemotherapy group experienced persistent vaginal dryness.³⁷

Chemotherapeutic agents used in the treatment of breast cancer can also cause VVA because of chemotherapy-induced ovarian failure. Premenopausal women account for 25% of all diagnosed breast cancer cases and are more likely to need systemic chemotherapy. The risk of permanent chemotherapy-induced ovarian failure is more common in women older than 40 years (49%-100%) than in those younger than 40 years (21%-71%).³⁹

Premenopausal women with hormone-sensitive (ER⁺) advanced breast cancer may be offered gonadotropin-releasing hormone agonists to induce a temporary menopause through suppression of ovarian function, with VVA as a potential adverse effect.⁴⁰ High-risk premenopausal women who areBRCA1/2⁺ sometimes choose bilateral oophorectomy, which in turn increases their likelihood of developing VVA.

Whether breast cancer survivors with VVA can be safely treated with low-dose vaginal estrogens remains controversial. Kendall et al⁴¹ addressed this question when they followed up 7 breast cancer survivors taking AIs to suppress estrogen levels. These women took 25-μg vaginal tablets of estradiol daily for 2 weeks and then twice weekly for severe symptoms of VVA. After 2 weeks of treatment, mean serum estradiol levels increased from a pretreatment value of 1.4 pg/mL or less to 19.6 pg/mL. The estrogen levels had decreased to less than 9.5 pg/mL by 4 weeks of therapy in most women, but only 2 women had pretreatment estradiol levels at week 7. If third-generation AIs decrease the levels of circulating estrogens more than earlier-generation AIs and at the same time improve survival, Kendall et al⁴¹ hypothesized that a small increase in circulating estradiol could worsen survival outcomes.Go to:

COMPLEMENTARY AND ALTERNATIVE MEDICINE

Complementary and alternative medicine products have been extensively studied in the treatment of hot flashes, but less information is available on their use in VVA. One study found that Vitamin E and phytoestrogen applied locally as a gel improved the symptoms of VVA.⁴² An evaluation of VVA was undertaken in a cross-sectional study of 60 women, half of whom had taken 1,25-dihydroxyvitamin D (0.5 μg/d of calcitriol) orally for at least 1 year and half of whom had not. The prevalence of vaginal atrophy was significantly higher in the group who did not use vitamin D, as measured by VMI and symptoms.⁴³

In a separate study, soy supplementation for the treatment of VVA was investigated. Phytoestrogens such as soy bind to ERs in the vagina and bladder. A randomized controlled trial evaluating dietary supplementation with 12 to 20 mg/d of soy showed no improvement in VMI.⁴⁴

Currently, well-established effective complementary and alternative medicine treatments for VVA are lacking.Go to:

FUTURE STUDIES

Future studies will continue to explore the use of even lower doses of vaginal estrogens. The efficacy and safety of 10-μg vaginal tablets of low-dose estradiol for the treatment of VVA were evaluated in a 2009 study; after 12 weeks of therapy, significant improvements in symptoms, pH, and VMI were observed, with no adverse effects.⁴⁵ In a recent study comparing treatment with 25 μg of estradiol, 10 μg of estradiol, and placebo, Bachmann et al⁴⁶ found that both active groups experienced improvement in vaginal atrophy symptoms, vaginal pH, and VMI, with greater improvements seen for the higher dose.

Interest in vaginal estriol products is strong because of the inverse relationship with breast cancer risk at a population level. Studies have shown that estriol improves symptoms of VVA and reduces the incidence of urinary tract infection. Exogenous estriol administration does not alter serum estradiol or follicle-stimulating hormone levels.^47–50

Studies are currently under way to evaluate newer selective ER modulators (SERMs), which specifically target urovaginal health without compromising breast health.⁵¹

Because moisturizers and lubricants also play a role in the treatment of VVA, better delivery systems for these nonhormonal vaginal treatments will likely be developed in the future.Go to:

CONCLUSION

Vulvovaginal atrophy, a common and often underreported condition, occurs in women who experience hypoestrogenic states. Systemic treatment, when prescribed for menopausal symptoms, may not be sufficient to control VVA. Local estrogens include creams, tablets, and rings, all of which are equally effective. Thus, patient preference will guide the choice. A growing number of women are at risk of developing VVA because of decreased use of systemic HT and increased use of SERMs, AIs, and chemotherapy in women with a history of breast cancer, for whom the safety of even low-dose vaginal estrogens has not been established.

Is vulvovaginal atrophy due to a lack of both estrogens and androgens?

Jan 22

Posted by Dr Colin Holloway

Menopause. 2016 Nov 21. [Epub ahead of print]

Is vulvovaginal atrophy due to a lack of both estrogens and androgens?

Labrie F¹, Martel C, Pelletier G.

Author information

• ¹1Laval University, Quebec City, Quebec, Canada 2Endoceutics Inc, Quebec City, Quebec, Canada.

Abstract

OBJECTIVE:

The aim of this study was to review the preclinical data showing the role of both estrogens and androgens in the physiology of the vagina, and, most likely, in vulvovaginal atrophy of menopause.

METHODS:

Mass spectrometry-based assays (validated according to the FDA guidelines) for the measurement of sex steroids, their precursors, and metabolites were used. In addition to fixation of the vagina for morphological examination, histomorphometry, immunocytochemistry, immunofluorescence, and quantitative reverse transcription polymerase chain reaction were performed.

RESULTS:

The vaginal epithelium of the animals receiving dehydroepiandrosterone (DHEA) was made of large multilayered columnar mucous cells showing distended cytoplasmic vacuoles representative of an androgenic effect. DHEA also stimulates collagen fiber compactness of the lamina propria (second layer)-an effect essentially due to an androgenic effect, whereas stimulation by DHEA of the muscularis in the third vaginal layer is approximately 70% due to the androgenic conversion of DHEA. Stimulation of the surface area of the nerve endings, on the contrary, is exclusively androgenic. Vaginal weight stimulation by DHEA is about 50% androgenic and 50% estrogenic.

CONCLUSIONS:

Practically all studies on the influence of steroid hormones in the vagina have focused on luminal epithelial cells. Since all estrogens and androgens in postmenopausal women are made intracellularly and derive from the conversion of circulating DHEA, it is of interest to observe from these preclinical data that DHEA exerts both estrogenic and androgenic activity in the three layers of the vagina, the stimulatory effect on nerve density being 100% androgenic. Taking vaginal weight as a global parameter, the stimulatory effect of DHEA in the rat vagina is about equally estrogenic and androgenic, thus illustrating the importance of androgens in vaginal morphology and function, and the likely importance of androgens in vulvovaginal atrophy of menopause.

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Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

Oct 15

Posted by Dr Colin HollowayVaginal dryness (atrophy) is common in the menopause, and is due to lack of Oestrogen. See my blog of Feb 17 – Vaginal problems.  For those who do not want oestrogen, or cannot take it for any reason, Oxytocin is a useful alternative. Oxytocin is known as the comfort hormone as it makes us feel warm and cuddly. (nursing mothers make lots of it)

Vaginal Problems

Feb 17

Post Reprod Health. 2015 May 19. pii: 2053369115577328. [Epub ahead of print]

Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

Al-Saqi SH¹, Uvnäs-Moberg K², Jonasson AF³.

Author information

Abstract

OBJECTIVE:

To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy.

DESIGN:

Double-blinded randomised controlled trial.

SETTING:

Healthy post-menopausal women in Stockholm, Sweden.

PARTICIPANTS:

Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden.

MAIN OUTCOME MEASURES:

The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation.

RESULTS:

The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089).

CONCLUSIONS:

Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy.

© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

KEYWORDS:

Estrogen; oxytocin; post-menopausal; vaginal atrophy; vagitocin

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DHEA for Urogenital Atrophy and Sexual Function

Jan 28

Posted by Dr Colin Holloway

DHEA for Urogenital Atrophy and Sexual Function

Susan R. Davis, MBBS, FRACP, PhD

Disclosures

January 15, 2015

Question

What is the current evidence on the use of intravaginal dehydroepiandrosterone (DHEA) in urogenital atrophy and sexual function?

Commentary from Susan R. Davis, MBBS, FRACP, PhD

Sex steroids are vital for the integrity of the urogenital tract (vagina, vulva, lower urinary tract, and supporting pelvic structures). These tissues are rich in estrogen and androgen receptors.^[1] In addition, estrogen and testosterone enhance blood flow to the genital tract,^[2] which is fundamental for genital sexual arousal and lubrication.^[3]

;The fall in estrogen at menopause and the gradual decline in androgen levels with age^[4] result in what is now described as genitourinary syndrome of menopause (GSM). This includes vulvovaginal atrophy (VVA) and an increase in vaginal pH.^[3] At a cellular level, there is a reduction in healthy vaginal epithelial superficial cells and an increase in parabasal cells. The increase in vaginal pH changes the vaginal microflora. Lactobacilli disappear, and as a consequence there is increased vulnerability to vaginal infection. Symptoms of VVA include vaginal dryness, irritation, itching, infection, and dyspareunia.^[5] This in turn leads to diminished sexual desire, arousal difficulties, diminished physical and emotional sexual satisfaction, and relationship issues.^[6]

Most postmenopausal women will experience some GSM symptoms.^[7] Symptoms of VVA can be effectively treated with either vaginal or systemic estrogen therapy.^[8] Estrogenization will thicken and revascularize the vaginal epithelium, lower vaginal pH, and normalize vaginal flora. The number of vaginal epithelial superficial cells will increase.^[8,9] Although data show that vaginal estrogen acts locally, thus minimizing systemic exposure to estrogen, some studies have shown blood estradiol levels increase with vaginal application.^[10,11,12] A two- to fivefold increase in serum estradiol has been reported after one week of vaginal administration of a 25 µg estradiol vaginal tablet or 1g of 0.625 mg conjugated estrogen cream.^[10] After 24 weeks of treatment, only 2% of women have estradiol levels outside the postmenopausal range.^[13]

Researchers have looked for alternative approaches for GSM management. In postmenopausal women, adrenal dehydro-epiandrosterone (DHEA) is an important precursor for extra-gonadal biosynthesis of estrone (by aromatization) and testosterone (by 5-alpha reduction). Casson and colleagues first studied the effects of a vaginal DHEA 150 mg pessary versus placebo in five premenopausal women as a mode of hormone delivery and reported an increase in blood levels of DHEA with this approach.^[14] The daily vaginal application of three different doses of DHEA cream (6.5 mg, 13 mg, and 23.5 mg) was studied for one week in postmenopausal women.^[15] Labrie and colleagues reported a decrease in vaginal pH, an improvement in the vaginal cell maturation index, and restoration of DHEA levels to the range for premenopausal women at the highest dose.^[15] The circulating levels of other sex steroids remained within the normal range for postmenopausal women.

A randomized controlled trial of the daily application of three different doses of vaginal DHEA ovules (3.25 mg, 6.5 mg, or 13 mg) was studied over 12 weeks in 218 postmenopausal women who met the entry criterion of dyspareunia. This single study has resulted in a number of publications to support the efficacy of this treatment for VVA.^{[16,17,18,19,20,21]} In these various publications, the investigators have reported an improvement in vaginal cytology and a reduction in pH. An analysis restricted to the women who fulfilled investigational criteria for a low percentage of vaginal epithelial cells and vaginal pH greater than 5 reported an increase in superficial cells and a reduction in pH with an associated improvement in dyspareunia compared with placebo.^[21] Sexual function was assessed by three questions in the Menopause Quality of Life Questionnaire (sexual desire, vaginal dryness during intercourse, or avoiding intimacy) and by the Abbreviated Sexual Function Questionnaire. At 12 weeks the total Menopause Quality of Life Questionnaire sexual domain score showed a significantly greater response for each treatment group versus placebo, with more mixed findings in the Abbreviated Sexual Function Question-naire.^[17]Vitality

DHEA Benefits Include Helping To Relieve Vaginal Pain Caused By Menopausal Dryness, Atrophy

Jan 5, 2016 12:01 AM By Susan Scutti

New research suggests a DHEA vaginal suppository for treating vaginal dryness may be one step closer to government approval. The DHEA formulation could provide an effective alternative for women hoping to ease their symptoms of menopause — without resorting to estrogen.

During perimenopause, vaginal tissues begin to atrophy, the lining thins and secretes less and less fluid, and the pH becomes more alkaline, explain the researchers. Not only do these signs of age lead to discomfort during sex, they also increase a woman’s susceptibility to infections and urinary problems. While hormonal treatments may help alleviate such symptoms, many women have a past history of cancer or higher genetic risk for reproductive cancers rendering such medicines unsafe.

As an alternatives to estrogen treatments, some women resort to non-hormonal lubricants. While these products may temporarily provide moisture and even ease sexual pains, they do not correct the physical problems producing the symptoms. By comparison, DHEA (dehydroepiandrosterone) is a precursor of estrogens and androgens and so can induce physical changes that protect the vagina, according to the researchers. That said, the DHEA product in this study is still considered “hormonal” by regulatory authorities, such as the Food and Drug Administration.

Safety Testing a New Product

For the study, a research team from EndoCeutics, a private bio-pharm company, recruited nearly 500 women to participate in a randomized, double-blind, placebo-controlled trial of its DHEA suppository product. The majority of the women, 84 percent, complained of moderate to severe vaginal dryness. The researchers divided the women, ranging in age from 40 to 80, into two groups: 325 women in the DHEA-treatment group and 157 in a placebo group. After a baseline gynecological test, the women used a daily suppository of either the DHEA or placebo, depending on their group, for 12 weeks.

Compared with the women using a placebo, the women who used the DHEA ovules experienced improvements. Their scores on a scale of 0 to 3 for pain during sex dropped 0.36 points more than the women using placebo and their scores improved by 0.27 points with regard to vaginal dryness. Importantly, the gynecologists who examined them saw 86 percent to 121 percent better improvements in vaginal secretions, integrity of the vaginal lining, lining thickness, and tissue color in the women who used DHEA, while their vaginal pH shifted 0.66 points toward acidity (a positive direction).

“The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6 percent of the participants,” noted the researchers in their study.

Importantly, this therapy has not been tested in patient at risk or with a history of breast cancer.

“Although this medication is considered ‘hormonal,’ the mechanism appears to be primarily local with minimal side effects beyond vaginal discharge from the suppository,” Dr. JoAnn V. Pinkerton, executive director of North American Menopause Society, stated in a press release.

Source: Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016.

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Vaginal oestrogen for overactive bladder in post-menopausal women.

Sep 16

Posted by Dr Colin HollowayBr J Nurs. 2015 Jun 11;24(11):582-5. doi: 10.12968/bjon.2015.24.11.582.

Vaginal oestrogen for overactive bladder in post-menopausal women.

Ostle Z¹.

Author information

Abstract

This article asks the question ‘Should nurses recommend vaginal oestrogen for overactive bladder in post-menopausal women?’ The article will review the evidence for use of vaginal oestrogen and consider the potential side-effects and risks. The main finding is that vaginal oestrogen is effective for treatment of overactive bladder in post-menopausal women with vaginal atrophy. However, vaginal atrophy is undertreated. This article identifies some of the barriers that may prevent diagnosis and treatment, and suggests changes in practice. Nurses should take the initiative and ask post-menopausal women about symptoms. Nurses should be trained to examine women, diagnose vaginal atrophy and discuss treatment.

KEYWORDS:

Continence; Overactive urinary bladder; Postmenopause; Urge urinary incontinence; Vagina

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Vaginal estrogen for genitourinary syndrome of menopause

Jun 10

Posted by Dr Colin Holloway

Vaginal problems are common in menopause, and that includes bladder and urinary symptoms. The fact is that both the bladder and vagina thrive under the influence of oestrogen, and so oestrogen is essential for both vagina and bladder health. Unfortunately, too many women suffer in silence over menopausal vaginal problems and do not discuss it with their doctors.

Vaginal estrogen for genitourinary syndrome of menopause: A systematic review

Obstetrics and Gynecology, 12/05/2014  Evidence Based Medicine  Review Article

Rahn DD, et al. – In this study, authors want to comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy–related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy–related symptoms and in patients at risk for estrogen–related neoplasia.

Methods

• MEDLINE and Cochrane databases were searched from inception to April 2013.
• Authors included randomized controlled trials and prospective comparative studies.
• Interventions and comparators included all commercially available vaginal estrogen products.
• Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.
• Authors double–screened 1,805 s, identifying 44 eligible studies.
• Discrepancies were adjudicated by a third reviewer.
• Studies were individually and collectively assessed for methodologic quality and strength of evidence.

Results

• Studies were extracted for participant, intervention, comparator, and outcomes data, including patient–reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events.
• Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI).
• Urinary tract infection rates decreased.
• The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high–dose conjugated equine estrogen cream.
• Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen.
• Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.

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Vaginal estrogen for genitourinary syndrome of menopause: A systematic review

May 20

Posted by Dr Colin Holloway

Vaginal problems are very common in menopausal women. Most suffer in silence unnecessarily. HRT helps, but sometimes a vaginal cream is needed. It helps the bladder as well, as a bonus. Read the evidence.

Vaginal estrogen for genitourinary syndrome of menopause: A systematic review
Obstetrics and Gynecology, 12/05/2014  Evidence Based Medicine  Review Article

Rahn DD, et al. – In this study, authors want to comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy–related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy–related symptoms and in patients at risk for estrogen–related neoplasia.

Methods

• MEDLINE and Cochrane databases were searched from inception to April 2013.
• Authors included randomized controlled trials and prospective comparative studies.
• Interventions and comparators included all commercially available vaginal estrogen products.
• Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators.
• Authors double–screened 1,805 s, identifying 44 eligible studies.
• Discrepancies were adjudicated by a third reviewer.
• Studies were individually and collectively assessed for methodologic quality and strength of evidence.

Results

• Studies were extracted for participant, intervention, comparator, and outcomes data, including patient–reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events.
• Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI).
• Urinary tract infection rates decreased.
• The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high–dose conjugated equine estrogen cream.
• Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen.
• Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer.

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Vaginal Health.

Feb 17

Posted by Dr Colin HollowayWe are now realizing that the vagina is an active and very complex organ, just like other organs such as the eye, ear, liver and so on. It tends to be neglected when we discuss good health, and most women suffer vaginal problems silently. Doctors don’t ask, women don’t tell. To have a good quality of  life in the peri- and post menopause, a healthy and properly functioning vagina is important.  Oestrogen is the most important hormone for vaginal health. Climacteric. 2012 Feb;15(1):36-44. doi: 10.3109/13697137.2011.647840. Epub 2011 Dec 14.

Vaginal Health: Insights, Views & Attitudes (VIVA) – results from an international survey.

Nappi RE, Kokot-Kierepa M.

Source

Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause Unit, Department of Obstetrics and Gynecology, IRCCS ‘S Matteo Foundation’, University of Pavia, Pavia, Italy.

Abstract

OBJECTIVE:

To assess knowledge of vaginal atrophy among women using the Vaginal Health: Insights, Views & Attitudes (VIVA) survey.

METHODS:

A structured online questionnaire was used to obtain information from 3520 postmenopausal women aged 55-65 years living in Great Britain, the United States, Canada, Sweden, Denmark, Finland, and Norway.

RESULTS:

In total, 45% of women reported experiencing vaginal symptoms. Only 4% of women attributed these symptoms to vaginal atrophy, and 63% failed to recognize vaginal atrophy as a chronic condition. Overall, 44% of respondents did not have a gynecologist, but this percentage varied between countries. Most women (75%) felt that vaginal atrophy had a negative impact on life, but this perception also showed country-specific differences. Most Finnish respondents (76%) were satisfied with the amount of information available about vaginal atrophy, compared with just 37-42% of women from other countries. Most women used over-the-counter products for vaginal atrophy symptoms, but specific means of treating the underlying cause were less well known. Almost half (46%) of all respondents lacked knowledge about local estrogen therapy, with women in Great Britain, the United States and Canada being most likely to lack knowledge of such treatment. Overall, 30% of women would consider taking local estrogen therapy, with vaginal tablets being the preferred option in all countries.

CONCLUSION:

Postmenopausal women have a low understanding of vaginal atrophy. Medical practitioners should proactively raise this topic, help patients to understand that vaginal atrophy is a chronic condition, and discuss treatment options. Country-specific approaches may be required.

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Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman’s life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae(ridges, folds) disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial.

AI = aromatase inhibitor; CI = confidence interval; ER = estrogen receptor; HT = hormone therapy; SERM = selective ER modulator; VMI = vaginal maturation index; VVA = vulvovaginal atrophy

Vulvovaginal atrophy (VVA) is a common condition, especially in postmenopausal women. Vaginal atrophy, atrophic vaginitis, and urogenital atrophy are other terms used to describe this constellation of symptoms associated with decreased estrogenization of the vulvovaginal tissue. Although treatment with topical estrogen is effective in alleviating symptoms, women frequently do not report symptoms and thus go untreated.

Common symptoms include vaginal dryness, irritation, postcoital bleeding, and soreness. These symptoms may be associated with vaginal discharge and dyspareunia. Urinary symptoms associated with VVA include frequency, urgency, and urge incontinence.

PREVALENCE

Vulvovaginal atrophy can occur at any time in a woman’s life cycle, although it is more common in the postmenopausal phase, a time of hypoestrogenism. Other causes of a hypoestrogenic state include lactation, various breast cancer treatments, and use of certain medications. In situations other than menopause, VVA may resolve spontaneously when estrogen levels are restored. After menopause, the elasticity of the vagina is reduced and connective tissue increases.A decline in estrogen level causes a decrease in vaginal blood flow and a decrease in vaginal lubrication. These changes can be reversed by the use of estrogens.

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Vaginal Problems

Feb 17

Posted by Dr Colin HollowayMayo Clin Proc. 2010 January; 85(1): 87–94. doi:  10.4065/mcp.2009.0413 PMCID: PMC2800285

Vulvovaginal Atrophy

Maire B. Mac Bride, MBBCh, Deborah J. Rhodes, MD, and Lynne T. Shuster, MD Author information ►Copyright and License information ► This article has been cited by other articles in PMC. Go to:

Abstract

Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman’s life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial.

AI = aromatase inhibitor; CI = confidence interval; ER = estrogen receptor; HT = hormone therapy; SERM = selective ER modulator; VMI = vaginal maturation index; VVA = vulvovaginal atrophy

Vulvovaginal atrophy (VVA) is a common condition, especially in postmenopausal women. Vaginal atrophy, atrophic vaginitis, and urogenital atrophy are other terms used to describe this constellation of symptoms associated with decreased estrogenization of the vulvovaginal tissue. Although treatment with topical estrogen is effective in alleviating symptoms, women frequently do not report symptoms and thus go untreated.^1,2

Common symptoms include vaginal dryness, irritation, postcoital bleeding, and soreness. These symptoms may be associated with vaginal discharge and dyspareunia. Urinary symptoms associated with VVA include frequency, urgency, and urge incontinence.Go to:

PREVALENCE

Vulvovaginal atrophy can occur at any time in a woman’s life cycle, although it is more common in the postmenopausal phase, a time of hypoestrogenism. Other causes of a hypoestrogenic state include lactation, various breast cancer treatments, and use of certain medications. In situations other than menopause, VVA may resolve spontaneously when estrogen levels are restored.

Numerous retrospective studies have evaluated the prevalence of symptoms of VVA (Table 1).^3–10Although these studies differ in type of symptoms elicited, study design, and study population, they provide a range of estimates of VVA prevalence. They all used self-reported symptoms of vaginal dryness to determine the prevalence of VVA. In general, the prevalence ranged from about 4% in the early premenopausal groups to 47% in the late postmenopausal group.

TABLE 1. Studies Assessing Prevalence of Vaginal Dryness

The prevalence of VVA in some subgroups of women can be much higher. In a cohort of breast cancer survivors, vaginal dryness was present in 23.4% of the premenopausal patients and in 61.5% of the postmenopausal patients.⁸Go to:

PHYSIOLOGY

Vulvovaginal atrophy occurs under conditions of hypoestrogenism. In the premenopausal state, estradiol levels fluctuate from 10 to 800 pg/mL (to convert to pmol/L, multiply by 3.671),¹¹ depending on when measured during the cycle. In the postmenopausal state, estradiol levels are typically less than 30 pg/mL. After menopause, circulating estradiol derives from estrone, which is peripherally converted in adipose tissue from adrenal androstenedione.

The vaginal epithelium is a stratified squamous epithelium, which until menopause is moist and thick with rugae. At menopause, with declining levels of estrogen, the vaginal epithelium thins. Fewer epithelial cells result in less exfoliation of cells into the vagina. As epithelial cells exfoliate and die, they release glycogen, which is hydrolyzed to glucose. Glucose, in turn, is broken down into lactic acid by the action of lactobacillus, a normal vaginal commensal organism. Without this cascade, the pH in the vagina rises, resulting in a loss of lactobacilli and an overgrowth of other bacteria, including group B streptococcus, staphylococci, coliforms, and diphtheroids¹² (Figure 1). These bacteria can cause symptomatic vaginal infections and inflammation. After menopause, the elasticity of the vagina is reduced and connective tissue increases.¹³ A decline in estrogen level causes a decrease in vaginal blood flow and a decrease in vaginal lubrication. These changes can be reversed by the use of estrogens.^14,15

FIGURE 1. Proposed cascade-of-effects mechanism for vulvovaginal atrophy.

The effects of endogenous estrogens on vulvovaginal tissues are mediated through estrogen receptors (ERs) α and β, found at sites throughout the urogenital area, including the vagina, vulva, labia, urethra, and bladder trigone. These sites, in turn, regulate transcription at specific areas on the DNA.¹⁶Go to:

SYMPTOMS

The initial symptom is often lack of lubrication during intercourse. Eventually, persistent vaginal dryness may occur. Thinning of the epithelial lining may also cause pruritus, soreness, and a stinging pain in the vaginal and vulvar area, which, in turn, may further contribute to dyspareunia. Vaginal spotting, due to small tears in the vaginal epithelium, may also occur. Women with VVA may report a thin yellow or grey watery discharge secondary to the rise in pH that accompanies VVA.¹⁷

Women with VVA often report symptoms such as urgency, frequency, nocturia, and urge incontinence. Urinalysis may show microscopic hematuria. Recurrent urinary tract infections can also result. Stress incontinence is commonly found in this age group of women, but current evidence suggests it is not directly attributable to VVA.¹⁸

Women do not always report their symptoms of VVA. They are more likely to report vaginal discharge and urinary urgency but are less likely to report vaginal itching, soreness, or dyspareunia. Women may not report symptoms because they are self-treating, feel the symptoms are not important enough, or are embarassed.¹⁹Go to:

CLINICAL FINDINGS

Clinical findings include atrophy of the labia majora and vaginal introitus. The labia minora may recede. Vulvar and vaginal mucosae may appear pale, shiny, and dry; if there is inflammation, they may appear reddened or pale with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. Vaginal shortening and narrowing tend to occur.²⁰

A thin watery yellow vaginal discharge may be observed. A urethral caruncle, a small, soft, smooth friable red outgrowth along the edge of the urethra, may develop.Go to:

CLINICAL TESTS

The diagnosis of VVA is a clinical one. However, 2 tests may be used to support the diagnosis: a vaginal pH and a vaginal maturation index (VMI). To assess pH, a piece of litmus paper is placed on the lateral vaginal wall until moistened. A pH of 4.6 or greater indicates VVA, assuming the patient does not have bacterial vaginosis. Premenopausal women without VVA typically have a pH of 4.5 or less.¹²

The VMI (Figure 2) is the criterion standard for VVA confirmation but is generally not used or needed in clinical practice. This test assesses the relative proportion of parabasal, intermediate, and superficial vaginal epithelial cell types. In premenopausal women, greater than 15% superficial cells would be considered normal; however, in postmenopausal women with VVA, the typical proportion would be less than 5%.

FIGURE 2. Photomicrographs of superficial and intermediate cells (top) and atrophic cells (bottom). (Papanicolaou stain; original magnification x20). Courtesy of the Mayo Cytopathology Laboratory. Go to:

DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes other conditions that cause chronic vaginal and vulvar itching, discharge, or pain (eg, vaginal infections, irritants, and vulvovaginal dermatoses). Vaginal infections can be caused by bacteria, viruses, protozoa, and fungi. The 3 most common vaginal infections are Candidavulvovaginitis, bacterial vaginosis, and trichomoniasis. Bacterial vaginosis may result from atrophic changes in the vagina. Irritants that can cause chronic vaginal itch include perfumes, any locally applied lubricant or moisturizer, and soaps. Vulvovaginal dermatoses, including lichen sclerosus, lichen planus, and lichen simplex chronicus, may cause similar symptoms.²¹ Cancer and precancerous lesions, including vulvar intraepithelial neoplasm, vulvar cancer, and extramammary Paget disease, are in the differential diagnosis of any localized areas of redness, thickening, or ulceration (Table 2). Biopsy should be performed if a malignancy is suspected or if the diagnosis is unclear.

TABLE 2. Differential Diagnosis for Symptoms of Vulvovaginal Atrophy Go to:

TREATMENT

Nonhormonal Treatments

Current over-the-counter treatments include nonhormonal vaginal moisturizers for VVA symptoms and lubricants for dyspareunia. Vaginal moisturizers, which are water based, are available as liquids, gels, or ovules inserted every few days. Vaginal moisturizers can be safely used long term, but they need to be used regularly for optimal effect.

Vaginal lubricants are shorter acting than moisturizers and are applied at the time of sexual activity to reduce dyspareunia. They can be either water or silicone based, with the water-based products being the most widely available. They are applied to the vaginal opening and/or to the penis and often require repeated application during sexual activity. Silicone-based lubricants require application of only a very small amount and last longer; however, they can interfere with erectile function in male partners. The choice of lubricant may depend on individual preferences and product availability.

Hormonal Treatments

On the basis of an evidence-based review of clinical trials examining available low-dose vaginal estrogen preparations for the treatment of VVA in postmenopausal women, The North American Menopause Society (NAMS) 2007 position statement noted that “the choice of therapy should be guided by clinical experience and patient preference.”²² NAMS also stated it is generally unnecessary to prescribe a progestogen in combination with low-dose vaginal estrogen to prevent endometrial hyperplasia or cancer.

On the basis of a meta-analysis of 19 randomized clinical trials involving 4162 postmenopausal women, the 2006 Cochrane Database of Systematic Reviews concluded that vaginal estrogen is an effective treatment for VVA²³ and that all forms, whether cream, ring, or tablet, appeared to relieve symptoms more effectively than nonhormonal gels and placebo. Differences observed between the treatments were in participant preferences.

Therefore, for symptomatic vaginal atrophy that does not respond to self-care measures, estrogen treatment is the standard of care, typically with vaginally administered local estrogens. Prescription vaginal estrogens are available as either estradiol or conjugated estrogens. In some countries outside the United States, vaginal estriol is also available.Go to:

SYSTEMIC ABSORPTION OF VAGINAL HORMONAL PREPARATIONS

An important concern about treatment safety relates to the extent of systemic absorption of vaginal estrogens. The conclusion from several studies comparing different doses of estradiol vaginal tablets^24,25 or different vaginal estrogen preparations (conjugated estrogens and estradiol vaginal tablets)²⁶ is that systemic absorption occurs, but to a limited extent. Labrie et al²⁶ showed that levels of estradiol increased on average from a baseline (pretreatment) level of 3 pg/mL to 17 pg/mL on day 7 of treatment for both estradiol vaginal tablets (25 μg) and conjugated estrogen cream (0.625 mg). Nilsson and Heimer²⁴ showed that, although plasma estradiol concentration diminished by the 14th day of daily treatment with 10 or 25 μg of vaginal estradiol, it was still statistically significantly higher than pretreatment levels. Some evidence shows that estradiol levels diminish over time when vaginal estrogens are used consistently.^24,25

Although vaginal estrogens applied as a cream, vaginal tablets, or a low-dose vaginal ring are systemically absorbed, the rise in serum estrogen levels appears to remain well below premenopausal levels. Nonetheless, this may be of concern to women with a history of breast or other hormonally sensitive cancersGo to:

PRACTICAL ISSUES

Because all low-dose vaginal estrogens appear comparable in efficacy for the treatment of VVA, the choice of estrogen formulation is determined by the clinician and by each woman’s preferences. Estrogen creams are currently the least costly and most widely used but require commitment to regular use for sustained effect. Dosing vaginal creams can be confusing because the dose of active estrogen cream is specified in milligrams, the dose of base cream in grams, and applicator volume in proportions. A simplified approach to dosing is provided in Table 3. The estradiol tablet is preferred by some to avoid the messiness of cream. The estradiol ring is long acting and requires less sustained effort to use; however, it requires dexterity to insert and remove and needs to be replaced every 3 months. The presence of a cystocele or rectocele may cause ring displacement.

TABLE 3. Vaginal Estrogen Products Go to:

SYSTEMIC ESTROGEN AGENTS AND VVA

Systemic estrogen therapy, in the form of patches, oral agents, or a higher-dose vaginal ring, is sometimes used for VVA, especially when the patient also has hot flashes. However, 10% to 20% of women may have residual VVA symptoms even while taking systemic estrogen.²⁷ These women will require administration of local vaginal estrogens alone or along with systemic therapy for relief of VVA symptoms.

Two studies have shown that oral hormone therapy (HT) may worsen symptoms of urinary incontinence. The Heart and Estrogen-Progestin Replacement Study found a higher risk of both urge (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.8; P<.001) and stress incontinence (odds ratio, 1.7; 95% CI, 1.5-2.1; P<.001) in the hormone-treated group vs the placebo group throughout the treatment period.²⁸

It has been suggested that urge incontinence worsened with HT because progesterone was a component. However, in the Women’s Health Initiative, 3 treatment groups were evaluated for urge incontinence (conjugated estrogens alone, conjugated estrogens with progesterone, and placebo). Women given conjugated estrogens alone were at increased risk of developing urge incontinence compared with those receiving placebo (relative risk, 1.32; 95% CI, 1.10-1.58), whereas the women given combination conjugated estrogens with progesterone were not (relative risk, 1.15; 95% CI, 0.99-1.34).²⁹ Thus, whether oral HT adversely affects urge urinary incontinence remains unclear.Go to:

BREAST CANCER AND VVA

Currently, more than 2 million women in the United States have a history of breast cancer. In breast cancer survivors, the estimated prevalence of vaginal atrophy, by symptom report, ranges from 23% to 61%.⁸ Prescribing even very low-dose localized estrogen treatments for these patients can cause concern because of the potential for systemic absorption.

Concern about the provision of any form of estrogen, either systemic or local, to breast cancer survivors contributes to the high incidence of VVA in women with breast cancer. Discontinuation of HT may trigger the onset of VVA symptoms.

Many surgical, endocrine, and chemotherapeutic treatments for breast cancer can cause or exacerbate VVA.^10,30–37 Tamoxifen acts as an estrogen antagonist or agonist depending on the target organ and menopausal status. In premenopausal women, tamoxifen may cause VVA by acting as an estrogen antagonist and blocking the naturally high levels of endogenous estrogen. In postmenopausal women, however, it acts as an estrogen agonist on the urogenital tract.³⁸

Raloxifene does not appear to have an effect on the urogenital area in either premenopausal or postmenopausal women. Davies et al³⁵ found no significant differences in incidence of VVA when comparing databases of postmenopausal women treated with raloxifene vs placebo.

Aromatase inhibitors (AIs) are prescribed as adjuvant systemic therapy to women with ER⁺ breast cancer. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) study, designed to compare outcomes in postmenopausal breast cancer survivors taking tamoxifen, anastrozole (an AI), or a combination of both, Cella et al¹⁰ demonstrated that vaginal dryness was more common in the group taking anastrozole than in the group taking tamoxifen (18.5% vs 9.1%). Dyspareunia was also more common in the anastrozole group (17.3% vs 8.1%).¹⁰

Chemotherapy itself can result in vaginal dryness and dyspareunia. In a randomized clinical trial comparing high-dose chemotherapy with standard-dose chemotherapy for breast cancer survivors, followed by radiotherapy and tamoxifen in all patients, more patients in the high-dose chemotherapy group experienced persistent vaginal dryness.³⁷

Chemotherapeutic agents used in the treatment of breast cancer can also cause VVA because of chemotherapy-induced ovarian failure. Premenopausal women account for 25% of all diagnosed breast cancer cases and are more likely to need systemic chemotherapy. The risk of permanent chemotherapy-induced ovarian failure is more common in women older than 40 years (49%-100%) than in those younger than 40 years (21%-71%).³⁹

Premenopausal women with hormone-sensitive (ER⁺) advanced breast cancer may be offered gonadotropin-releasing hormone agonists to induce a temporary menopause through suppression of ovarian function, with VVA as a potential adverse effect.⁴⁰ High-risk premenopausal women who areBRCA1/2⁺ sometimes choose bilateral oophorectomy, which in turn increases their likelihood of developing VVA.

Whether breast cancer survivors with VVA can be safely treated with low-dose vaginal estrogens remains controversial. Kendall et al⁴¹ addressed this question when they followed up 7 breast cancer survivors taking AIs to suppress estrogen levels. These women took 25-μg vaginal tablets of estradiol daily for 2 weeks and then twice weekly for severe symptoms of VVA. After 2 weeks of treatment, mean serum estradiol levels increased from a pretreatment value of 1.4 pg/mL or less to 19.6 pg/mL. The estrogen levels had decreased to less than 9.5 pg/mL by 4 weeks of therapy in most women, but only 2 women had pretreatment estradiol levels at week 7. If third-generation AIs decrease the levels of circulating estrogens more than earlier-generation AIs and at the same time improve survival, Kendall et al⁴¹ hypothesized that a small increase in circulating estradiol could worsen survival outcomes.Go to:

COMPLEMENTARY AND ALTERNATIVE MEDICINE

Complementary and alternative medicine products have been extensively studied in the treatment of hot flashes, but less information is available on their use in VVA. One study found that Vitamin E and phytoestrogen applied locally as a gel improved the symptoms of VVA.⁴² An evaluation of VVA was undertaken in a cross-sectional study of 60 women, half of whom had taken 1,25-dihydroxyvitamin D (0.5 μg/d of calcitriol) orally for at least 1 year and half of whom had not. The prevalence of vaginal atrophy was significantly higher in the group who did not use vitamin D, as measured by VMI and symptoms.⁴³

In a separate study, soy supplementation for the treatment of VVA was investigated. Phytoestrogens such as soy bind to ERs in the vagina and bladder. A randomized controlled trial evaluating dietary supplementation with 12 to 20 mg/d of soy showed no improvement in VMI.⁴⁴

Currently, well-established effective complementary and alternative medicine treatments for VVA are lacking.Go to:

FUTURE STUDIES

Future studies will continue to explore the use of even lower doses of vaginal estrogens. The efficacy and safety of 10-μg vaginal tablets of low-dose estradiol for the treatment of VVA were evaluated in a 2009 study; after 12 weeks of therapy, significant improvements in symptoms, pH, and VMI were observed, with no adverse effects.⁴⁵ In a recent study comparing treatment with 25 μg of estradiol, 10 μg of estradiol, and placebo, Bachmann et al⁴⁶ found that both active groups experienced improvement in vaginal atrophy symptoms, vaginal pH, and VMI, with greater improvements seen for the higher dose.

Interest in vaginal estriol products is strong because of the inverse relationship with breast cancer risk at a population level. Studies have shown that estriol improves symptoms of VVA and reduces the incidence of urinary tract infection. Exogenous estriol administration does not alter serum estradiol or follicle-stimulating hormone levels.^47–50

Studies are currently under way to evaluate newer selective ER modulators (SERMs), which specifically target urovaginal health without compromising breast health.⁵¹

Because moisturizers and lubricants also play a role in the treatment of VVA, better delivery systems for these nonhormonal vaginal treatments will likely be developed in the future.Go to:

CONCLUSION

Vulvovaginal atrophy, a common and often underreported condition, occurs in women who experience hypoestrogenic states. Systemic treatment, when prescribed for menopausal symptoms, may not be sufficient to control VVA. Local estrogens include creams, tablets, and rings, all of which are equally effective. Thus, patient preference will guide the choice. A growing number of women are at risk of developing VVA because of decreased use of systemic HT and increased use of SERMs, AIs, and chemotherapy in women with a history of breast cancer, for whom the safety of even low-dose vaginal estrogens has not been established.

Future research on VVA will likely explore the use of much lower doses of vaginal estrogens, seek to develop newer delivery systems for nonhormonal therapy, and develop SERMs that preferentially target urogenital tissues.

Future research on VVA will likely explore the use of much lower doses of vaginal estrogens, seek to develop newer delivery systems for nonhormonal therapy, and develop SERMs that preferentially target urogenital tissues.