Author Archives: Dr Colin Holloway

These common drugs may increase dementia risk

Top News in Internal Medicine

I am going to be in South Africa for the next 2 weeks, attending the 50th reunion of my medical school graduation class. I will be giving the Keynote address at the Alumni Symposium on how I helped prevent an environmental disaster in the 1980s. Dr Anne Nixon and Dr Mahdu will be looking after my patients in my absence.

These common drugs may increase dementia risk

Healthline/Medical News Today | June 25, 2019

A common class of drugs that doctors prescribe for a number of conditions—from bladder problems to Parkinson’s disease and depression—may increase a person’s risk of dementia, a large new study concludes.

New research by scientists from the University of Nottingham in the United Kingdom has analyzed the link between a certain class of drugs and the risk of dementia. The drugs in question, called anticholinergics, work by inhibiting a chemical messenger called acetylcholine.

Their effect is to help relax or contract muscles, and doctors can prescribe them to help treat bladder conditions, gastrointestinal problems, and some of the symptoms of Parkinson’s disease.

In their new study, which looked at data from tens of thousands of participants, the researchers concluded that anticholinergics may increase a person’s risk of developing dementia. The National Institute for Health Research funded this study, and the scientists published their findings yesterday in JAMA Internal Medicine.

An almost 50% increase in risk

For their study, lead researcher professor Carol Coupland and team analyzed the medical records of 58,769 people with dementia and 225,574 people without dementia. They were all 55 years old or above at baseline.

Among those with dementia, 63% were women and the average age was 82. For each person with dementia, the researchers found five control matches of the same age and sex and who attended the same general practice to receive medical care.

Coupland and colleagues sourced the data from the QResearch database and looked at medical records from between January 1, 2004 and January 31, 2016.

The researchers found that anticholinergic drugs in general were associated with a higher risk of dementia. More specifically, however, anticholinergic antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, bladder drugs, and epilepsy drugs were associated with the highest increase in risk.

Among these, the most frequently prescribed drugs were antidepressants, anti-vertigo drugs, and bladder antimuscarinic drugs (for the treatment of overactive bladder).

These results remained even after the researchers controlled for confounding variables (or known risk factors for dementia), including body mass index (BMI), smoking status, alcohol use, cardiovascular problems, and the use of other medication, such as antihypertensive drugs.

All in all, the researchers concluded that people aged 55 or over who had taken strong anticholinergics on a daily basis for at least 3 years had an almost 50% higher chance of developing dementia than people who had not used this type of medication.

“This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties,” explains study co-author professor Tom Dening.

“However,” he warns, “it’s important that [people] taking medications of this kind don’t just stop them abruptly, as this may be much more harmful. If [people] have concerns, then they should discuss them with their doctor to consider the pros and cons of the treatment they are receiving.”

‘Risks should be carefully considered’

To assess the strength of anticholinergic drugs and how often the participants took them, the team looked at available information about prescriptions over a period of 10 years. However, they note that this is an observational study, so they cannot confirm whether the drugs are directly responsible for the increased risk of dementia. The researchers add that doctors may have prescribed some of these drugs to their patients precisely for the treatment of very early dementia symptoms.

Nevertheless, Coupland argues that the “study adds further evidence of the potential risks associated with strong anticholinergic drugs, particularly antidepressants, bladder antimuscarinic drugs, anti-Parkinson’s drugs, and epilepsy drugs.”

“The risks of this type of medication should be carefully considered by health-care professionals alongside the benefits when the drugs are prescribed and alternative treatments should be considered where possible.”

—Professor Carol Coupland

“These findings also highlight the importance of carrying out regular medication reviews. We found a greater risk for people diagnosed with dementia before the age of 80, which indicates that anticholinergic drugs should be prescribed with caution in middle-aged people as well as in older people,” she concludes.

Sexual hormone oestradiol protects female brain in mid-life

We constantly hear the negative side of oestrogen in women, and rarely the positive side. This will interest most of you.

Sexual hormone oestradiol protects female brain in mid-life

Recent research suggests that increased visceral fat – that is body fat surrounding a number of important internal organs such as the liver, pancreas and intestines – carries the risk of cognitive impairment in later life. “Our goal was to investigate whether excess organ fat is associated with a reduction in the structural networks and storage capacity of our brain throughout its lifetime. We also wanted to find out whether this interaction can be influenced by oestradiol,” said Rachel Zsido.

Oestradiol is a hormone consisting of cholesterol and is the strongest of the three naturally produced oestrogens. It is the most important hormone found in the female body and has many amazing functions – it contributes decisively to the maintenance of the female reproductive system. Men also produce oestradiol, but in much smaller amounts. In both sexes, oestradiol is also produced by fatty tissue, the brain and the walls of blood vessels. It also has a vasodilative and antioxidant effect. Oestradiol can help maintain myelin architecture – and thus the membrane that protects our nerves.

Although visceral fat and estradiol appear to play opposite roles in the healthy ageing process of the brain, it remains unclear how and at what point they interfere with brain structure. To solve this mystery, Zsido and her colleagues examined a large data set of healthy adults aged between 20 and 80, 501 men and 473 women, from the LIFE study. “We looked at the brain structure and body fat of the volunteers on images taken from the magnetic resonance tomograph, as well as their memory and oestradiol levels in the blood. Our results suggest that increased organ fat expands the negative influence of aging on brain networks in men and women. We have also found that men prepare this organ fat earlier, while women are particularly affected in mid-life,” the scientist explains.

“The decrease in oestradiol in this middle phase of life accelerates the normal aging process. It seems, however, that oestradiol protects women’s brains from structural damage to the gray matter during the middle of life”, adds Julia Sacher, who along with her research group is investigating the effects of hormonal changes on mood, emotional well-being and cognition. “We took a closer look at a subgroup of women between the ages of 35 and 55 and found that a low level of oestradiol is associated with weaker memory performance in the middle of life. This is also the age range in which the transition to menopause occurs, which is initially characterised by abrupt oestradiol fluctuations and finally by a stop in the reproductive phase. We therefore believe that the pre-menopausal phase provides an important window of opportunity to prevent accelerated brain aging and the development of neurodegenerative diseases such as dementia or depression in women.

Hormones important in risk recognition for dementia or depression

A second joint study led by Julia Sacher and Steffi Riedel-Heller from the Institute for Social Medicine, Occupational Medicine and Public Health (ISAP) also showed a decisive interaction between unfavourable metabolic states and another important sex hormone, testosterone. The team found that elevated testosterone levels and changes in body weight have different effects on women’s susceptibility to depression before and after menopause. “Together, the results from both studies emphasize the need to further consider sex differences and sex hormones when investigating the risk of neurodegenerative diseases,” summarizes Julia Sacher. This is particularly important in mid-life, as this transitional phase offers women a special opportunity for prevention.

Abstract

Importance:

Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss.

Objectives:

To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure.

Design, setting, and participants:

Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 2018.

Exposures:

Serum estradiol levels from fasting blood and visceral adipose tissue volume from T1-weighted magnetic resonance imaging (MRI).

Main outcomes and measures:

Brain network covariance (individual loading on structural network derived from T1-weighted MRI) and memory performance (composite score from the Consortium to Establish a Registry for Alzheimer Disease [CERAD] verbal episodic memory test on learning [score range, 0-30], recall [score range, 0-10], and recognition [score range, 0-20]).

Results:

Final analyses included data from 473 women (mean [SD] age, 50.10 [15.63] years) and 501 men (mean [SD] age, 51.24 [15.67] years). Visceral adipose tissue was associated with an exacerbation of the negative association of aging with network covariance for women (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P = .001) and men (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P < .001). Estradiol level was associated with a reduction in the negative association of VAT with network covariance in women (interaction term β = 0.63; 95% bias-corrected bootstrap CI, 0.14-1.12; P = .01), with no significant association in men. In the female midlife subgroup (age range, 35-55 years, when menopause transition occurs), low estradiol levels were associated with lower memory network covariance (Cohen d = 0.61; t80 = 2.76; P = .007) and worse memory performance (Cohen d = 0.63; t76 = 2.76; P = .007).

Conclusions and relevance:

This study reports a novel association between VAT, estradiol, and structural brain networks as a potential mechanism underlying cognitive decline in women. These findings appear to highlight the need for sex-specific strategies, including VAT and hormonal screening during midlife, to support healthy cognitive aging.

Reference

Zsido RG, Heinrich M, Slavich GM, Beyer F, Kharabian Masouleh S, Kratzsch J, Raschpichler M, Mueller K, Scharrer U, Löffler M, Schroeter ML, Stumvoll M, Villringer A, Witte AV, Sacher J.  Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults. JAMA Netw Open. 2019 Jun 5;2(6):e196126. doi: 10.1001/jamanetworkopen.2019.6126.

More on Oestrogen and Breast Cancer

Breast Cancer (Auckl). 2019 May 15;13:1178223419844198. doi: 10.1177/1178223419844198. eCollection 2019.

The word apoptosis means: Apoptosis removes cells during development. It also eliminates pre-cancerous and virus-infected cells, although “successful” cancer cells manage to escape apoptosis so they can continue dividing. Apoptosis maintains the balance of cells in the human body and is particularly important in the immune system.

Pro-Apoptotic Effects of Estetrol on Long-Term Estrogen-Deprived Breast Cancer Cells and at Low Doses on Hormone-Sensitive Cells.

Yue W1, Verhoeven C2, Bernnink HC2, Wang JP1, Santen RJ1.

Author information

1Department of Medicine, Division of Endocrinology & Metabolism, University of Virginia Health Systems, Charlottesville, VA, USA.2Pantarhei Oncology, Zeist, The Netherlands.

Abstract

Purpose:

Postmenopausal women with estrogen receptor-positive breast cancers often respond initially to tamoxifen or aromatase inhibitor therapy. Resistance to these treatments usually develops within 12 to 18 months. Clinical studies have demonstrated that high-dose estrogen can induce regression of these endocrine-resistant tumors. However, side-effects of high-dose estradiol (E2) or diethylstilbestrol (DES) limit their usage. Estetrol (E4) is the most abundant estrogen during pregnancy and has a long half-life and a low potential for side-effects. Estetrol might then provide benefits similar to DES on tumor regression but with lesser toxicity.

Methods:

In this study, we systematically evaluated the effects of E4 on cell proliferation and apoptosis in wild-type MCF-7 and long-term estrogen-deprived (LTED) MCF-7 cells and compared its effects with E2 and estriol (E3).

Results:

Estetrol induced apoptosis in LTED cells but stimulated growth of MCF-7 cells at concentrations from 10-11 to 10-8 M. These effects of E4 are similar to those of E2 but require much higher doses. Differing from E2, E4 at 10-12 M induced apoptosis in MCF-7 cells and another pregnancy estrogen, E3, acted similarly. No antagonistic effect of E4 or E3 against E2 occurred when they were combined.

Conclusions:

The pro-apoptotic effects of E4 and E3 on LTED cells and at low doses on MCF-7 cells indicate that these steroids could be used as therapeutic agents for endocrine-resistant or sensitive breast cancer.

J Endocrinol. 2015 Jan;224(1):85-95. doi: 10.1530/JOE-14-0549. Epub 2014 Oct 30.

Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation.

Gérard C1, Blacher S1, Communal L1, Courtin A1, Tskitishvili E1, Mestdagt M1, Munaut C1, Noel A1, Gompel A2, Péqueux C3, Foidart JM1.

Author information

1Laboratory of Tumor and Development BiologyGIGA-Cancer, Institute of Pathology, University of Liège, CHU-B23, B-4000 Liège, BelgiumINSERM-UMRS 938Université Pierre et Marie Curie (UPMC), F-75005 Paris, FranceGynaecological Endocrinology UnitParis Descartes University, Hôpitaux Universitaires, F-75006 Paris, France.2Laboratory of Tumor and Development BiologyGIGA-Cancer, Institute of Pathology, University of Liège, CHU-B23, B-4000 Liège, BelgiumINSERM-UMRS 938Université Pierre et Marie Curie (UPMC), F-75005 Paris, FranceGynaecological Endocrinology UnitParis Descartes University, Hôpitaux Universitaires, F-75006 Paris, France Laboratory of Tumor and Development BiologyGIGA-Cancer, Institute of Pathology, University of Liège, CHU-B23, B-4000 Liège, BelgiumINSERM-UMRS 938Université Pierre et Marie Curie (UPMC), F-75005 Paris, FranceGynaecological Endocrinology UnitParis Descartes University, Hôpitaux Universitaires, F-75006 Paris, France.3Laboratory of Tumor and Development BiologyGIGA-Cancer, Institute of Pathology, University of Liège, CHU-B23, B-4000 Liège, BelgiumINSERM-UMRS 938Université Pierre et Marie Curie (UPMC), F-75005 Paris, FranceGynaecological Endocrinology UnitParis Descartes University, Hôpitaux Universitaires, F-75006 Paris, France C.Pequeux@ulg.ac.be.

Abstract

Estetrol (E4) is a natural estrogen produced exclusively by the human fetal liver during pregnancy. Its physiological activity remains unknown. In contrast to ethinyl estradiol and estradiol (E2), E4 has a minimal impact on liver cell activity and could provide a better safety profile in contraception or hormone therapy. The aim of this study was to delineate if E4 exhibits an activity profile distinct from that of E2 on mammary gland. Compared with E2, E4 acted as a low-affinity estrogen in both human in vitro and murine in vivo models. E4 was 100 times less potent than E2 to stimulate the proliferation of human breast epithelial (HBE) cells and murine mammary gland in vitro and in vivo respectively. This effect was prevented by fulvestrant and tamoxifen, supporting the notion that ERα (ESR1) is the main mediator of the estrogenic effect of E4 on the breast. Interestingly, when E4 was administered along with E2, it significantly antagonized the strong stimulatory effect of E2 on HBE cell proliferation and on the growth of mammary ducts. This study characterizes for the first time the impact of E4 on mammary gland. Our results highlight that E4 is less potent than E2 and exhibits antagonistic properties toward the proliferative effect of E2 on breast epithelial cells. These data support E4 as a potential new estrogen for clinical use with a reduced impact on breast proliferation

Oncotarget. 2015 Jul 10;6(19):17621-36.

Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms.

Gérard C1, Mestdagt M1, Tskitishvili E1, Communal L2, Gompel A2,3, Silva E4, Arnal JF5, Lenfant F5, Noel A1, Foidart JM1, Péqueux C1.

Author information

1Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.2Gynaecological Endocrinology Unit, Paris Descartes University, Hôpitaux Universitaires, Paris, France.3INSERM U938, Université Pierre et Marie Curie, Paris.4Institute of Environment, Health and Societies, Brunel University London, Uxbridge, United Kingdom.5INSERM U1048, Institut des Maladies Métaboliques et Cardiovasculaires, University of Toulouse, UPS, Toulouse, France.

Abstract

Increased risk of breast cancer is a critical side effect associated with the use of a menopausal hormone therapy (MHT). Estetrol (E4) is a natural estrogen produced by the human fetal liver and is a promising compound for clinical use in MHT. However, its impact on breast cancer is controversial and poorly defined. In this preclinical study, we show that E4 acts as a weak estrogen by stimulating the growth of hormone-dependent breast cancer only at concentrations exceeding menopausal therapeutic needs. E4 presents also an antitumor activity by decreasing the strong proliferative effect of estradiol (E2). While estrogen receptor alpha (ERα) is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extra-nuclear signaling pathway are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. Altogether, our results highlight that E4 has a limited impact on breast cancer and may offer a safe therapeutic window for the treatment of menopausal symptoms.

More on oestrogen and breast cancer.

My medical career has always been guided by what is best and safest for my patients. I read extensively and keep very up to date with the latest information regarding health, and hormones in particular. Some of it can be very technical, and a knowledge of biochemistry, statistics and epidemiology is necessary. I do not expect the average person to be Au fait with these subjects.

I began using natural progesterone before it became popular, and now it is accepted as the safest form of progesterone. I used hormones as troches (transdermal), when most form of hormones were given as a pill. Now transdermal is recognized as the safest form of giving hormones.

I have written this blog for over 10 years, so that I can share my knowledge with you, my readers, so that you may have a credible source of information about the things that effect you.

In a previous blog, I mentioned that there are 3 oestrogens women produce: Oestrone (E1), Oestradiol(E2) and Oestriol(E3). There is actually a 4th oestrogen, estetrol (E4), which is produced in large amounts in pregnant women – which could be one of the reasons breast cancer is very rare in pregnancy, and the more pregnancies women have, the lower the risk of breast cancer.

Biest, the oestrogen used in troches, is made up of 80% Oestriol(E3), and 20% Oestradiol (E2). As you can see if you wade through the research I have published on my blogs recently, E3 counteracts any negative effects on the breasts that E2 might have. This is probably part of the reason that my statistics for the amount of breast cancer my patients get is below the national average. Those of you who are interested, and that includes the many doctors who subscribe to my blog, can wade through all the details below, and to follow. Otherwise, just take it as read.

Estriol: Its Weakness is Its Strength

August 2008

By Olivia A.M. Franks, ND and Jonathan V. Wright, MD

Estriol, an estrogen that has virtually been ignored by the mainstream medical community, is one of the three principal estrogens produced by the body. Estriol was originally thought to have little significance due to its weak estrogenic activity when compared with estrone and estradiol. Nonetheless, research has found that its weakness may very well be its strength. Studies suggest that when the lower-potency estrogen, estriol, is administered topically, it does not increase the risk of hormone-dependent cancers of the breast or endometrium (uterine lining).1-3 However, having weaker estrogenic effects does not mean that estriol has none of the benefits that come with more potent estrogens. Studies suggest that estriol reduces symptoms of menopause, such as hot flashes and vaginal dryness, but with a better safety profile compared with more potent estrogens.1,4,5 This makes estriol a better choice for bioidentical hormone-replacement treatment regimes. That is not all this ‘weak’ hormone is good for! Research suggests that estriol has benefits for bone density, heart health, multiple sclerosis, and postmenopausal urinary tract health.6-12 In this article, we will review the attributes of this ‘weaker’ estrogen, and why this estrogen is currently in the news. What you need to know The body naturally makes three estrogen hormones—estradiol, estrone, and estriol. Since estriol possesses the weakest estrogenic effects of the three, it has been largely overlooked by the medical community. Many studies show that estriol offers a wealth of potential health benefits—without the dangers that sometimes accompany higher-potency estrogens and synthetic or horse-derived hormones. Studies suggest that estriol helps relieve menopausal symptoms while benefitting bone and urinary tract health. Estriol may also help improve cardiovascular risk factors and even shows promise in reducing the brain lesions of multiple sclerosis. The most reliable way to measure estriol levels is through 24-hour urine collection. Despite abundant evidence to the contrary, the FDA has recently claimed that estriol is not safe. You can act now to help preserve consumers’ access to bioidentical hormones such as estriol by visiting http://www.anh-usa.org/home-coalition-redirect/. Fear of cancer prevents many women from restoring youthful hormone levels. When applied through the topical (transdermal) route, estriol is not associated with increased cancer risk. Other methods women can use to prevent hormone-related cancers include consuming abundant vitamin D, cruciferous vegetables, soy, D-glucarate, and lignans, while minimizing meat and high-fat dairy intake. Estriol and Hormone Replacement Therapy If you are on hormone-replacement therapy (HRT) and have never heard of estriol, you might be wondering why not? Before the 1970s, estriol was thought to have significance only during pregnancy. Levels of estriol are elevated in pregnancy up to 1,000 times compared with normal non-pregnant levels. In the 1960s, we saw the beginning of hormone-replacement therapy with patented equine estrogens such as Premarin® and synthetic progestins as found in Provera®. By the 1990s, one-third of menopausal women were taking Premarin®. Research uncovered the increased incidence of breast cancer, increased risk of blood clotting, and increased cardiovascular risk associated with the use of these horse-derived and synthetic hormones (used in combination in the patented medication Prempro®).13 The medical community began to wonder if using hormones from pregnant horses was such a good idea. In an effort to find a safer alternative, many patients and practitioners began looking into ‘natural’ hormone-replacement treatment using bioidentical hormones, which are identical to those produced naturally within the body. Bioidentical-hormone replacement was pioneered in the 1980s as a treatment for menopause by Dr. Jonathan Wright in Washington state. Interest in estriol increased as it was discovered that estriol was safer than horse-derived and synthetic hormones in relation to cardiovascular health and potentially cancer risk. Unfortunately, many doctors have not adopted its use, and many bioidentical hormone-replacement regimes use only estradiol, a more potent estrogen with increased associated risks. The benefits of estriol may, in part, be explained by the mixed pro-estrogenic and anti-estrogenic effects of this interesting estrogen hormone. Scientists Melamed et al. investigated the mixture of stimulating and non-stimulating effects posed by estriol upon estrogen receptors. When estriol is given together with estradiol, the estradiol-specific stimulation to cells is decreased. This little-appreciated scientific fact helps to explain how estriol can reduce pro-carcinogenic effects of more powerful estrogens like estradiol. However, when estriol is given alone over a long period of time, it can produce a more complete pro-estrogenic effect, explaining why symptom relief is achieved when menopausal women take estriol.2 Experimental studies suggest that both estriol and tamoxifen (a synthetic anti-estrogen) have protective effects against radiation-induced cancer of the breast.14 Safety Concerns Most of the research cited in this article used oral estrogen as the route of administration. However, for enhanced safety, topical estriol would be a better choice. Several studies have shown that transdermal estrogen confers less health risk as a route of administration than oral estrogen.3,21-25 Clinical experience of many doctors over the past 20-30 years suggests that transdermal estrogen is also more effective for some women. This is largely thought to be due to the ‘first-pass effect’—meaning that orally ingested drugs are often first metabolized in the liver, before having any activity in the body. Orally ingested estrogen hormones are among these drugs that are first metabolized in the liver before exerting their effects in the body. Physicians experienced in hormone replacement often observe that women treated with oral estrogens show high levels of estrogen metabolites in 24-hour urine specimens, suggesting that most of the orally ingested hormones are being excreted. In addition, several studies suggest that bioidentical estrogen has less health risk when given with low doses of bioidentical progesterone.26,27 In a prospective study funded by the US Army and performed at the Public Health Institute, Berkeley, California, researchers compared estriol levels during pregnancy with breast cancer incidence 40 years later. Results revealed that of the 15,000 women entered in the study, those with the highest levels of estriol relative to other estrogens during pregnancy had the lowest cancer risk. In other words, as the relative level of estriol increased during pregnancy, risk of breast cancer decreased 40 years later. In fact, women with the highest level of estriol during pregnancy had 58% lower risk for breast cancer compared with women who had the lowest serum estriol levels. The authors also noted that Asian and Hispanic women had higher estriol levels compared with other racial groups. Interestingly, Asian and Hispanic women have the lowest breast cancer rates. The authors concluded, “If confirmed, these results could lead to breast cancer prevention or treatment regimens that seek to block estradiol estrogen action using estriol, similar to treatment based on the synthetic anti-estrogen tamoxifen.”15 In another study, Takahashi et al. studied the safety of estriol treatment for menopausal symptoms. Fifty-three women with either surgically induced or natural menopause were given 2 mg of oral estriol/day for 12 months. Endometrial and breast assessments done with endometrial biopsy and breast ultrasound, respectively, found normal results in all women. The authors concluded that over a 12-month period, “estriol appeared to be safe and effective in relieving symptoms of menopausal women.”1 In one investigation, 52 postmenopausal women were given 2 mg, 4 mg, 6 mg, or 8 mg/day of oral estriol for six months. In all patients, vasomotor symptoms of menopause (such as hot flashes) were decreased. The most improvement was experienced by women taking the highest dose of 8 mg. There were no signs of endometrial hyperplasia confirmed by endometrial biopsy over the six-month treatment period. Mammograms were obtained on six of the patients who had mammary hyperplasia at the study’s outset, and no further changes were seen.8 Although the oral route of administration of estriol appears relatively safe over the short-term, the transdermal route is preferred for long-term use. For example, Weiderpass et al. found an increased risk of endometrial atypical hyperplasia and endometrial cancer with oral use of estriol, but not with transdermal estriol over at least a five-year period. Compared with no use of estriol, those who took oral estriol for at least five years had a significantly greater risk, compared with individuals who did not take any estriol. Women using topical estriol for at least five years did not have any increased risk.3 As you will read in the “Safety” box, several studies suggest that the use of topical natural progesterone cream may further reduce the risk to the endometrium.16-18 Henry Lemon, MD, a women’s cancer specialist, took this research one step further and developed the concept of the estrogen quotient—the ratio of estriol to the sum of estradiol and estrone (estriol/estrone+estradiol). By looking at this ratio of ‘good’ estrogen to ‘bad’ estrogen, a physician can evaluate breast cancer risk and prescribe estrogen replacement better tailored to the individual to reduce cancer risk. The estrogen quotient can be evaluated from a 24-hour urine hormone panel.19,20 Estriol Reduces Markers of Cardiovascular Risk Growing evidence suggests that estriol may offer protective benefits for the cardiovascular system. For instance, Takahashi et al. found that some women with natural menopause given 2 mg/day oral estriol for 12 months had a significant decrease in both systolic and diastolic blood pressure.1 Another study compared the use of oral estriol at a dose of 2 mg/day for 10 months in 20 postmenopausal and 29 elderly women. Some of the elderly women had decreases in total cholesterol and triglycerides and an increase in beneficial high-density lipoprotein (HDL).7 Estriol Improves Bone Mineral Status in Women With Osteoporosis A Japanese study involving 75 postmenopausal women found that after 50 weeks of treatment with 2 mg/day of oral estriol cyclically and 800 mg/day of calcium lactate, women had an increase in bone mineral density, a decrease in menopausal symptoms, and no increased risk of endometrial hyperplasia (tissue overgrowth that may precede cancer).6 Similarly, Nishibe et al. investigated treatment of postmenopausal and elderly women with 2 mg/day of oral estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate alone. The bone mineral density significantly increased in women who received estriol, whereas the women who did not take estriol experienced a decrease in bone mineral density.7 Estriol Reduces Brain Lesions of Multiple Sclerosis The high levels of estriol during pregnancy have been known to alleviate some autoimmune conditions due to its ability to shift immune response.9 For instance, Sicotte et al. at the Reed Neurological Research Center in Los Angeles investigated the effects of pregnancy-level doses of estriol (8 mg/day) in non-pregnant women with multiple sclerosis (MS). Cerebral MRI images showed a significant reduction of gadolinium-enhancing cerebral lesions from multiple sclerosis. These lesions increased when treatment stopped and decreased when treatment was restarted.28 Gadolinium is a contrast agent used in certain MRI studies; gadolinium-enhancing lesions are associated with an increased inflammatory response marking disease progression in patients with MS. Lowered amount of these lesions seen on MRI with gadolinium contrast would equate to a decrease in disease progression. This effect may also apply to men with autoimmune conditions. Another team of researchers from the Reed Neurological Research Center in Los Angeles found that estriol treatment ameliorates experimental autoimmune encephalomyelitis (EAE) in males, compared with placebo treatment.29 EAE is an experimental demyelinating inflammatory disease that shares numerous characteristics with MS. Estriol treatment also resulted in a decrease of proinflammatory immune markers. This is very promising news for patients and their doctors who are struggling to treat challenging neurological conditions associated with inflammation. Estriol Protects Urinary Health in Postmenopausal Women Postmenopausal women who suffer from incontinence or recurrent urinary tract infections will be pleased to know that estriol offers benefit in the context of these troublesome conditions. In a prospective, randomized, placebo-controlled study, 88 women were given 2 mg intravaginal estriol suppositories (once daily for two weeks, then twice weekly for six months) or placebo. Of the women in the estriol group, 68% reported improvement in symptoms of incontinence. In addition, measurements of mean maximal urethral pressure and mean urethral closure pressure were significantly improved.10 In another randomized, double-blind, placebo-controlled trial, women with recurrent urinary tract infections (UTI) were given either intravaginal estriol cream (containing 0.5 mg estriol, once daily for two weeks, then twice weekly for eight months) or placebo. The incidence of urinary tract infection was dramatically reduced in the estriol group compared with placebo (0.5 versus 5.9 episodes per year).11 Measurement of Estriol Hormones produced by the body are secreted in pulses, while hormones taken transdermally or orally will initially be very high and slowly decline over the course of the day. This scientific reality makes testing for estriol at a single point in time—as would be the case for saliva or serum testing—very inaccurate. There are too many variables: When did your body last put out a pulse of the hormone under investigation? When did you take your hormone-replacement therapy? Estriol in particular does not last very long in the blood. In fact, the half-life of estriol has been shown to be between 3.6 and 64 minutes.30 The more accurate way to assess estriol is by collecting what is excreted during a 24-hour urine collection. This form of testing ensures that we have an accurate value that is not affected by the fluctuations of the day, because we are measuring 24 hours’ worth of hormone production. Estriol in the News Recently, the FDA made claims that estriol—a hormone naturally produced by women’s bodies—is not safe, even though the FDA did admit at a press conference that no adverse effects from estriol have ever been reported. After reading about the benefits of estriol that research has uncovered, it is hard to understand why the FDA would want to take this more protective estrogen off the market and out of reach of the many thousands of women seeking relief from menopausal and postmenopausal symptoms. This recent attack on estriol also includes all bioidentical hormones produced by compounding pharmacies. Why are these substances such a threat? This is not the first time the FDA has made attacks on unpatented natural substances. Bioidentical and therefore unpatentable hormones are a threat to the income of big drug companies. The fees paid by these big drug companies are a large portion of FDA income. Would you not say that there is a conflict of interest here? Why would any woman want to take horse estrogen or chemically imprecise, yet patentable estrogen rather than estrogen that is identical to that produced by women’s own bodies? This is even more questionable in the light of all the negative research showing increased health risks from these FDA-approved substances. And is it not the job of the FDA to make sure that women get safe and effective medicine? It seems the FDA has largely lost sight of its original goals. For more information on this and to take action, please visit the HOME (Hands Off My Estrogen!) Coalition website at http://www.homecoalition.org. Summary Estriol, once thought of as insignificant and weak, actually has protective effects against stronger estrogens. For this reason, it is a relatively safer choice for bioidentical hormone-replacement therapy. We have learned that safety is also increased by using topical administration instead of oral administration, and by balancing estrogen with progesterone. Estriol has benefits beyond treating typical postmenopausal symptoms. Estriol offers potential benefit for people with MS, postmenopausal women prone to urinary tract infection or incontinence, and menopausal/ postmenopausal women with osteoporosis. It would be a great shame to lose this wonderful tool before it was ever fully utilized. If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370. Is Fear of Cancer a Reason to Be Deprived of Hormones? As women enter their menopausal years, they face a difficult decision. The body’s natural production of estrogen, progesterone, dehydroepiandrosterone, and other critical hormones needed to maintain health and vigor rapidly declines.31,32 While individual effects of menopause vary widely, most women suffer because their glands no longer produce the hormones needed to regulate critical physiological processes. Depression, irritability, and short-term memory lapses are common menopausal complaints, along with hot flashes, night sweats, and insomnia.31 Concern about cancer is the primary reason why women do not restore their hormones to more youthful levels. Like much of what we eat, estrogen and testosterone affect cell proliferation. Does that mean we should shrivel up, degenerate, and die from these sex hormone deficiencies we all face as a part of “normal” aging? Based on the data showing how people may reduce their rate of cancer and favorably affect estrogen metabolism in a way that points to cancer prevention (by consuming lots of cruciferous vegetables, for example), it is difficult to buy into the argument that natural sex hormones should only be enjoyed by the young. Large human population studies show huge reductions in cancer risk and specific protective mechanisms against estrogen’s negative pathways when vitamin D,32-36 cruciferous vegetables (a source of indole-3-carbinol, or I3C),37-42 soy,43-48 D-glucarate,49-52 and lignans53-55 are consumed. Dramatic cancer rate reductions also occur when red meat, high-fat dairy, and other deleterious foods are reduced or eliminated from the diet.43,55-58 Misconceptions generated by conflicting studies and media hype have created an environment in which aging people suffer the agonies and shortened life spans caused by sex hormone imbalances, yet do nothing to correct this due to fear of cancer. When one looks at what the real cancer risk factors are, it would appear that altering one’s lifestyle at any age would result in significant reductions in malignant disease, including those who properly restore their natural hormone balance to reflect a more youthful range. The Real Cause of Breast Cancer To enable members to fully understand the carcinogenic effects of aging, we have reprinted on this page a chart showing women’s breast cancer risk by age.59 A quick look at this chart clearly documents that aging is the primary cause of breast cancer. The good news is that the gene expression changes involved in the development of breast cancer can be favorably altered by taking low-cost nutrients like vitamin D60 in the dose of 1,000 IU to 10,000 IU/day, based on individual need. Risk of Developing Breast Cancer by Age59 By age 25: 1 in 19,608
By age 30: 1 in 2,525
By age 40: 1 in 217
By age 45: 1 in 93
By age 50: 1 in 50
By age 55: 1 in 33
By age 60: 1 in 24
By age 65: 1 in 17
By age 70: 1 in 14
By age 75: 1 in 11
By age 80: 1 in 10
By age 85: 1 in 9 During the younger years, when breast cancer is virtually non-existent, we enjoy high levels of our sex hormones (estrogen, progesterone, dehydroepiandrosterone, and testosterone). As we age and hormone levels decline, breast cancer risks increase. The reason “aging” causes cancer is that the genes in our cells that regulate cell proliferation become increasingly mutated. The accumulation of mutations to our cells’ regulatory genes is the underlying cause of cancer.61 It is encouraging to know that there are low-cost nutrients that favorably restore healthy gene function and reduce our risk of cancer in the process. A newly published study cites evidence that vitamin D can exert its cancer-preventing effect by counteracting the growth-promoting effect of estrogens.62 Vitamin D also exerts its cancer-preventive influence by helping to control cell differentiation and inducing normal programmed cell disposal (apoptosis).62 Based on the enormity of these data, it would appear that aging humans can restore many of the hormones they need to sustain life—without encountering adverse effects. Having said this, we have to remind readers that there are still no long-term safety data on the safety of even weak exogenously administered estrogens like estriol. Based on the totality of evidence that exists to date, it would appear that the estriol confers many benefits, while definitive protective measures against breast and other cancers can easily be incorporated into a healthy lifestyle. —William Faloon
References
1. Takahashi K, Okada M, Ozaki T, et al. Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause. Hum Reprod. 2000 May;15(5):1028-36. 2. Melamed M, Castano E, Notides AC, Sasson S. Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol. Mol Endocrinol. 1997 Nov;11(12):1868-78. 3. Weiderpass E, Baron JA, Adami HO, et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet. 1999 May 29;353(9167):1824-8. 4. Yang TS, Tsan SH, Chang SP, Ng HT. Efficacy and safety of estriol replacement therapy for climacteric women. Zhonghua Yi Xue Za Zhi (Taipei). 1995 May;55(5):386-91. 5. Lauritzen C. Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints. Horm Metab Res. 1987 Nov;19(11):579-84. 6. Minaguchi H, Uemura T, Shirasu K, et al. Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study. J Obstet Gynaecol Res. 1996 Jun;22(3):259-65. 7. Nishibe A, Morimoto S, Hirota K, et al. Effect of estriol and bone mineral density of lumbar vertebrae in elderly and postmenopausal women. Nippon Ronen Igakkai Zasshi. 1996 May;33(5):353-9. 8. Tzingounis VA, Aksu MF, Greenblatt RB. Estriol in the management of the menopause. JAMA. 1978 Apr 21;239(16):1638-41. 9. Soldan SS, varez Retuerto AI, Sicotte NL, Voskuhl RR. Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estriol. J Immunol. 2003 Dec 1;171(11):6267-74. 10. Dessole S, Rubattu G, Ambrosini G et al. Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. Menopause. 2004 Jan;11(1):49-56. 11. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. 12. Kano H, Hayashi T, Sumi D, et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002 May 24;71(1):31-42. 13. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. 14. Lemon HM, Kumar PF, Peterson C, Rodriguez-Sierra JF, Abbo KM. Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen. Cancer. 1989 May 1;63(9):1685-92. 15. Siiteri PK, Sholtz RI, Cirillo PM, et al. Prospective study of estrogens during pregnancy and risk of breast cancer. Public Health Institute, Berkeley, CA.[Findings presented at Dept of Defense Breast Cancer Research Meeting] 2002 Sept. 26. 16. Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Fertil Steril. 2003 Jan;79(1):221-2. 17. Burry KA. Topical progesterone. Menopause. 2003 Jul-Aug;10(4):373-4; author reply 377-9. 18. Lee JR. Topical progesterone. Menopause. 2003 Jul-Aug;10(4):374-7; author reply 377-9. 19. Wright JV. Bio-identical steroid hormone replacement: selected observations from 23 years of clinical and laboratory practice. Ann N Y Acad Sci. 2005 Dec;1057:506-24. 20. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27. 21. Nahoul K, Dehennin L, Jondet M, Roger M. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas. 1993 May;16(3):185-202. 22. Eilertsen AL, Hoibraaten E, Os I, et al. The effects of oral and transdermal hormone replacement therapy on C-reactive protein levels and other inflammatory markers in women with high risk of thrombosis. Maturitas. 2005 Oct 16;52(2):111-8. 23. Vongpatanasin W, Tuncel M, Wang Z, et al. Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women. J Am Coll Cardiol. 2003 Apr 16;41(8):1358-63. 24. Abbas A, Fadel PJ, Wang Z, et al. Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women. Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):e164-7. 25. Dew JE, Wren BG, Eden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric. 2003 Mar;6(1):45-52. 26. Moyer DL, de LB, Driguez P, Pez JP. Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. Fertil Steril. 1993 May;59(5):992-7. 27. Gillet JY, Andre G, Faguer B, et al. Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study. Maturitas. 1994 Aug;19(2):103-15. 28. Sicotte NL, Liva SM, Klutch R, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol. 2002 Oct;52(4):421-8. 29. Palaszynski KM, Liu H, Loo KK, Voskuhl RR. Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol. 2004 Apr;149(1-2):84-9. 30. Longcope C. Estriol production and metabolism in normal women. J Steroid Biochem. 1984 Apr;20(4B):959-62. 31. Freeman EW, Sammel MD, Lin H, et al. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol. 2007 Aug;110(2 Pt 1):230-40. 32. Von Bamberger CM. Prevention and anti-aging in endocrinology. MMW Fortschr Med. 2007 Mar 1;149(9):33-5. 33. de Lyra EC, da Silva IA, Katayama ML, et al. 25(OH)D3 and 1,25(OH)2D3 serum concentration and breast tissue expression of 1alpha-hydroxylase, 24-hydroxylase and Vitamin D receptor in women with and without breast cancer. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):184-92. 34. Bertone-Johnson ER, Chen WY, Holick MF, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1991-7. 35. Cross HS, Kallay E, Lechner D, et al. Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas. J Nutr. 2004 May;134(5):1207S-12S. 36. O’Kelly J, Koeffler HP. Vitamin D analogs and breast cancer. Recent Results Cancer Res. 2003;164:333-48. 37. Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1953-60. 38. Linseisen J, Piller R, Hermann S, Chang-Claude J. Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2004 Jun 10;110(2):284-90. 39. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3′-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7. 40. Muti P, Bradlow HL, Micheli A, et al. Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women. Epidemiology. 2000 Nov;11(6):635-40. 41. Fowke JH, Longcope C, Hebert JR. Brassica vegetable consumption shifts estrogen metabolism in healthy postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):773-9. 42. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997 May 21;89(10):718-23. 43. Cui X, Dai Q, Tseng M, et al. Dietary patterns and breast cancer risk in the shanghai breast cancer study. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1443-8. 44. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003 Jun 18;95(12):906-13. 45. Lu LJ, Cree M, Josyula S, et al. Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res. 2000 Mar 1;60(5):1299-305. 46. Setchell KD. Soy isoflavones—benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J Am Coll Nutr. 2001 Oct;20(5 Suppl):354S-62S. 47. Hirose K, Tajima K, Hamajima N, et al. A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status. Jpn J Cancer Res. 1995 Feb;86(2):146-54. 48. Barnes S. Effect of genistein on in vitro and in vivo models of cancer. J Nutr. 1995 Mar;125(3 Suppl):777S-83S. 49. Anon. Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9. 50. Heerdt AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventive agent in breast cancer. Isr J Med Sci. 1995 Feb;31(2-3):101-5. 51. Slaga TJ, Quillici-Timmcke J. D-Glucarate: A Nutrient Against Cancer. Columbus, Ohio: McGraw-Hill;1999. 52. Walaszek Z, Hanausek-Walaszek M, Minton JP, Webb TE. Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis. 1986 Sep;7(9):1463-6. 53. McCann SE, Muti P, Vito D, et al. Dietary lignan intakes and risk of pre- and postmenopausal breast cancer. Int J Cancer. 2004 Sep 1;111(3):440-3. 54. Boccardo F, Lunardi G, Guglielmini P et al. Serum enterolactone levels and the risk of breast cancer in women with palpable cysts. Eur J Cancer. 2004 Jan;40(1):84-9. 55. dos SS, I, Mangtani P, McCormack V, et al. Phyto-oestrogen intake and breast cancer risk in South Asian women in England: findings from a population-based case-control study. Cancer Causes Control. 2004 Oct;15(8):805-18. 56. Tavani A, Giordano L, Gallus S, et al. Consumption of sweet foods and breast cancer risk in Italy. Ann Oncol. 2006 Feb;17(2):341-5. 57. Lajous M, Willett W, Lazcano-Ponce E, et al. Glycemic load, glycemic index, and the risk of breast cancer among Mexican women. Cancer Causes Control. 2005 Dec;16(10):1165-9. 58. Moorman PG, Terry PD. Consumption of dairy products and the risk of breast cancer: a review of the literature. Am J Clin Nutr. 2004 Jul;80(1):5-14. 59. Simone CB. Cancer and Nutrition. Lawrenceville, NJ: Princeton Institute; 2005. 60. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91. 61. Haber D. Roads leading to breast cancer. N Engl J Med. 2000 Nov 23;343(21):1566-8. 62. Abbas S, Nieters A, Linseisen J, et al. Vitamin D receptor gene polymorphisms and haplotypes and postmenopausal breast cancer risk. Breast Cancer Res. 2008 Apr 17;10(2):R31.

More information re HRT and Breast cancer.

The Australian Menopause Society released this response to this latest scare re: HRT and BC. It more or less repeats something I wrote earlier today. Something I should mention – there are three oestrogens women produce, of which oestrone is the most likely to produce BC. Oestriol is considered protective and anti-breast cancer. Oestradiol is in the middle somewhere, but can be converted into oestrone. When I prescribe Biest or Triest to my patients, 80% of the oestrogen used is Oestriol, the safest . However, it is a weak oestrogen and so the addition of some oestradiol is often necessary.

Media

MHT and breast cancer risk – Lancet 29 August 2019

A new paper on menopausal hormone therapy (MHT) and breast cancer risk has just been published in the Lancet. The International Menopause Society has released the following comment:

“Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence.”

Collaborative Group on Hormonal Factors in Breast Cancer.

The Lancet 29th August 2019

The comment by the International Menopause Society in response to this publication is available here

Current president of the International Menopause Society is Professor Susan Davis, Past-President of the AMS.  

Is there new information that menopausal hormone therapy (MHT) substantially increases breast cancer risk as suggested by a paper published in the Lancet this month (1) and should women be worried?

  • Much of the information regarding breast cancer risk and MHT reported in this paper is not new, although findings in relation to estrogen-only therapy do differ from those reported in the Women’s Health Initiative randomised trial. It is important to note that, because of when the data included in this report was collected, most of the MHT regimens were different from those currently recommended.
  • This paper provides an important public health message about obesity and breast cancer risk.
  • The reported the effects of MHT for women who go through early menopause (before the age of 45 years) must be seen in the context of what is “normal” for women of this age.
  • Potential breast cancer risk is one component of the benefit : risk analysis of MHT use for an individual woman which needs to include symptom severity and the potential beneficial effects of MHT on bone and cardiovascular health.

The Women’s Health Initiative randomised clinical trials contributed substantially to our understanding of the benefits and risks of MHT. This new paper primarily reports the findings from large observational studies to which women were recruited and followed for several years. In these studies the use of MHT, including dose and formulation, was a personal choice, as opposed to randomised controlled trials where women have been randomly allocated to MHT or placebo. Women who developed breast cancer (cases) were identified in the large prospective cohort studies and then matched with multiple controls per case. The authors have tried to minimise bias in their analyses, but it is important to recognise that observational studies include unquantifiable confounding effects, for which corrections cannot be made, and so as in all studies, there are limitations.

The paper reports slightly larger risks for estrogen+progestogen therapy compared with the findings of the randomised clinical trials they have listed in their paper (1). A smaller, but statistically significant, risk of breast cancer is also reported for estrogen-only use, whereas the randomised trials did not report an increase in breast cancer risk with estrogen-only therapy.

It is extremely important to note that this paper does not inform us of the impact of current recommended MHT prescribing practices on breast cancer risk. 

The median year of diagnosis of breast cancer cases from North America (25% of the included data) was 1999, and for the European studies, 2007, with one as early as 1981. With an average use of 10 years of MHT in current users at diagnosis, and 7 years in past users, much of the exposure to MHT preceded the first publication of the Women’s Health Initiative study, after which prescribing practices changed substantially. Consequently, virtually all of the included information pertains to MHT formulations and doses known to have adverse breast effects that are no longer recommended. Specifically, the use of the progestogens medroxyprogesterone acetate and norethisterone (norethindrone) is now discouraged because of their known adverse effects, but these account for nearly all of the data for combined estrogen-progestogen therapy included in the paper. The one analysis of data from prospective studies of the effects of different progestogens provides inadequate data to draw conclusions about the effects of the preferred progestogens, progesterone (50 included cases) and dydrogesterone (253 included cases).  Additionally, the majority of cases were women who took oral estrogen, which results in high blood levels of the hormone estrone, whereas transdermal therapy does not (2). Estrone is not only the main estrogen produced by postmenopausal women, but levels are higher in overweight/obese women, such that estrone may be a key factor linking obesity with breast cancer.

A take home message of this paper should be that obesity is an important risk factor for breast cancer

Considering the high proportion of women over 50 who are overweight or obese, and the progressive increase in we are seeing in the prevalence of obesity, this is an important public health message.

Research findings in context for women experiencing early /premature menopause

A particular concern about the possible interpretation of the findings of this paper pertains the analysis to women who commenced MHT before the age of 45 years.

10% of women experience menopause before 45 years. However the “norm” for women younger than 45 is to be premenopausal. In this study MHT users younger than 45 years were compared with postmenopausal women younger than 45 years not using MHT, whereas in terms of breast cancer risk, the clinically meaningful comparator would be age-matched premenopausal women. 

As the authors of this paper have previously reported, women who become postmenopausal before the age of 45 years have a 30% lower risk of breast cancer compared with women who remain premenopausal until the age of 45 years (3). In the current paper the authors report that young postmenopausal women who use MHT have an increase in breast cancer risk compared with young postmenopausal women who are not using MHT. But what they fail to highlight is that for young women, MHT restores their breast cancer risk to approximately what it would have been if they had not gone through an early menopause. This is extremely important as menopause before the age of 45 years is associated with a greater risk of premature death from all causes, including premature death from cardiovascular disease (4), as well as substantially greater risk of osteoporosis and fragility fracture in later life. Therefore early/premature menopause is a relative hormone deficiency state, and in these young women, MHT is a hormone restorative therapy.

The average age of menopause is 51.5 years, with most women experiencing menopause between the ages of 45 and 55 years. Women aged 45-54 years who are premenopausal are at greater risk of breast cancer than age-matched counterparts who have become postmenopausal (RR at age 45–54 years 1·43, 1·33–1·52, p<0·001).  However, for women in this age group who have become postmenopausal, MHT also restores (reduces) the risks of conditions such as bone loss, diabetes and cardiovascular disease to those of women of the same age who are still premenopausal. If one then takes into account relief of vasomotor symptoms, there is much to be considered in weighing up the benefit-to-risk ratio for an individual woman.

Recommendations from the IMS

Women enter menopause across a range of ages, with diverse symptoms and health risk profiles.

The International Menopause Society advocates the comprehensive assessment of women, including attention to modifying risk factors for chronic disease such as being overweight or obese, the importance of which have been highlighted in this Lancet paper.  The benefits and risks of MHT differ according to the timing of menopause such that individualisation of therapy is essential. As prescribing practices have changed significantly over the last decade, further research is needed to determine the impact of currently recommended regimens.

References

  1. Collaborative Group on Hormonal Factors in Breast Cancer.
    Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019.
  2. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8 Suppl 1:3-63.
  3. Collaborative Group on Hormonal Factors in Breast Cancer.
    Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012;13:1141-51.
  4. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R et al. Association of Age at Onset of Menopause and Time Since Onset of Menopause With Cardiovascular Outcomes, Intermediate Vascular Traits, and All-Cause Mortality: A Systematic Review and Meta-analysis. JAMA Cardiol 2016;1:767-76.

Here we go again- HRT and Breast Cancer risk.

There has been media coverage of a study by Professor Emily Banks that says HRT increases menopausal women’s risk of breast cancer (BC). This comes up frequently, as women are naturally concerned about any connection between the two. This means I will spend the next month reassuring my patients that the way I do it is very safe, and I will explain the reason I can say that below.

The study published in today’s media had a number of problems with it – they used mainly synthetic progestogen, and not natural progesterone. I have known (from many published studies, so it is no secret) that the synthetic progesterones increase women’s rick of BC. Natural progesterone does not. So why would any doctor give it to menopausal women? Beats me. Ask them for an explanation.

Secondly, most of the hormones used were in pill form. We have known for many years the HRT must be given transdermally (creams, patches or troches), and not as a pill. So why do doctors use oral forms of HRT (Like Livial, Xyvion, estalis, Kliovance, Kliogest, Femoston, Progynova, Premarin) Beats me. Ask them for an explanation.

Third factor – using one size fit all means many women get the wrong dose of hormone – tailoring the dose has to be better, so women get the lowest dose that works for them.

Personal experience – I have been using these BHRT for the last 25 years, in over 4500 women, and doing a statistical study of these women, I get about 4% BC incidence. BC occurs in about 13% of Australian women, so I know that there is no increase in BC in the women I treat – in fact the opposite. Unfortunately some of my patients do end up with BC – but it is below the national incidence.

Now lets look at the opposite – lives saved. Most women die from heart disease (estimate about 50%), not BC. HRT reduces women’s risk of heart disease significantly, so it actually saves lives. Then there is the quality of life issues, relationships saved and general well being on HRT.

Here are the relevant articles which I have published before: note they come from impeccable sources: You can find anything on the internet, so information should only come from respected medical journals, internationally respected researchers, and grade 1 universities.

Climacteric. 2012 Apr;15 Suppl 1:3-10.

What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone.

Simon JA.

Source

Department of Obstetrics and Gynecology, George Washington University, Washington, DC 20036, USA.

Abstract

The original conclusions of the Women’s Health Initiative study have been questioned as a result of the availability of age-stratified data. Initial concerns regarding the risk of coronary heart disease (CHD) in association with the use of hormone replacement therapy (HRT) have been replaced with concerns regarding thromboembolic disease, encompassing venous thromboembolism (VTE), particularly in younger postmenopausal women, and stroke, particularly in older women. The original publication of the study results led to a dramatic decrease in the use of oral HRT; however, the use of transdermal HRT has increased over recent years.

 Guidelines from the North American Menopause Society, the Endocrine Society, the International Menopause Society, and specific guidelines from the Menopause and Andropause Society for the management of menopausal women with a personal or family history of VTE all contain positive statements regarding both transdermal estradiol and micronized progesterone.

Unlike oral estrogens, transdermal estradiol has been shown not to increase the risk of VTE, or stroke (doses ≤ 50 μg), and to confer a significantly lower risk for gallbladder disease. Unlike some progestogens, progesterone is also not associated with an increased risk of VTE, or with an increased risk of breast cancer. Based on these data, which are now included in the guidelines, the use of transdermal estradiol and micronized progesterone could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis, and possibly even breast cancer associated with oral HRT use

They reviewed all the guidelines form the major medical bodies that deal with hormones, and concluded that using transdermal oestrogen and micronised progesterone is the safest form of HRT.  Micronised is the form of natural progesterone used in Bioidentical HRT. This is not to be confused with progestogens, which is used mainly in the synthetic forms of HRT Progestogens largely are known as Provera, {Medroxyprgesterone acetate- MPA: or Norethisterone (Primolut-N).

This is the most recent medical publication re safety of HRT:Menopause. 2016 Jul 25. [Epub ahead of print]

Reduced risk of breast cancer mortality in women using postmenopausal hormone therapy: a Finnish nationwide comparative study.

Mikkola TS1, Savolainen-Peltonen H, Tuomikoski P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O.

Author information

  • 11Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland 2Folkhälsan Research Center, Biomedicum, Helsinki, Finland 3EPID Research Oy, Espoo, Finland 4Information Services Department, National Institute for Health and Welfare, Helsinki, Finland.

Abstract

OBJECTIVE:

Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT).

METHODS:

In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population.

RESULTS:

The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality.

CONCLUSIONS:

In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.Menopause. 2015 Sep;22(9):976-83. doi: 10.1097/GME.0000000000000450.

Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality.

Mikkola TS1, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O.

Author information

Abstract

OBJECTIVE:

Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland.

METHODS:

A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population.

RESULTS:

Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older.

CONCLUSIONS:

In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.

Am J Public Health. 2013 Sep;103(9):1583-8. doi: 10.2105/AJPH.2013.301295. Epub 2013 Jul 18.

The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years.

Sarrel PM1, Njike VY, Vinante V, Katz DL.

Author information

1 Departments of Obstetrics and Gynecology and Psychiatry, Yale University School of Medicine, New Haven, CT, USA. philip.sarrel@yale.edu

Abstract

OBJECTIVES:

We examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years.

METHODS:

We derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women’s Health Initiative randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011.

RESULTS:

Over a 10-year span, starting in 2002, a minimum of 18 601 and as many as 91 610 postmenopausal women died prematurely because of the avoidance of estrogen therapy (ET).

CONCLUSIONS:

ET in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. Our data indicate an associated annual mortality toll in the thousands of women aged 50 to 59 years. Informed discussion between these women and their health care providers about the effects of ET is a matter of considerable urgency

There’s no evidence caesarean sections cause autism or ADHD

There has been reports in the media today that Caesareans can cause Autism. This article helps.

Caesarean delivery alone does not contribute to the odds of a child developing autism or ADHD. Aditya Romansa

There’s no evidence caesarean sections cause autism or ADHD

August 29, 2019 6.03am AEST

Author

  1. Andrew Whitehouse Bennett Chair of Autism, Telethon Kids Institute, Univeristy of Western Australia, University of Western Australia

Disclosure statement

Andrew Whitehouse receives funding from the National Health and Medical Research Council, the Australian Research Council and the Autism CRC.

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University of Western Australia provides funding as a founding partner of The Conversation AU.

A new study that combines data from over 20 million births has found that a caesarean section delivery is associated with autism spectrum disorder (autism) and attention-deficit hyperactivity disorder (ADHD).

However, the study does not indicate that caesarean section deliveries cause autism or ADHD. The truth is much more difficult to decipher, and provides an excellent case study for the old adage that correlation doesn’t equal causation.


Read more: Clearing up confusion between correlation and causation


Remind me, what are these disorders?

Autism and ADHD are what we call neurodevelopmental disorders. This means they have clear differences in behavioural development, which we presume are due to brain differences.

In the case of autism, behavioural differences occur in the part of the brain primarily responsible for social and communication development. For ADHD, these differences affect the ability to control and direct attention.

The exact reasons why the brain develops differently are not entirely clear. Studies in twins, which are able to help us understand the role of genetic and environmental influences on a given trait, have shown that both autism and ADHD involve a large genetic component.

However, these studies have also indicated that environmental influences, such as bacterial or viral infections during pregnancy, may play a role in the development of these conditions, most likely through interactions with genetic make-up.


Read more: What causes autism? What we know, don’t know and suspect


What did this study find?

The association between certain caesarean sections and autism has been known for close to two decades. Any possible link with ADHD has received comparatively less research, but there have still be numerous studies in this area.

Today’s study, published in the journal JAMA Network Open, combines all of the studies conducted previously into a single analysis. This “meta-analysis” then allows the researchers to come up with a single estimate of how strong the association between caesarean sections, autism and ADHD may be.

The researchers were looking for a pattern that warrants further investigation. freestocks.org

In this case, the meta-analysis included over 20 million people. It found children born via caesarean section had an increase in odds of being diagnosed with autism or ADHD in early childhood.

The associations were scientifically robust, but very small. Children delivered via caesarean section were 1.33 times more likely to be diagnosed with autism and 1.17 times more likely to be diagnosed with ADHD.

When the prevalence of these conditions is already relatively low (around 1% for autism, and 7% for ADHD), this increase in odds is not substantial. In the instance of autism, this is a shift in odds from a 1% prevalence to 1.33%. This shift is not consequential and certainly does not call for any change in our clinical practice.


Read more: What you need to know to understand risk estimates


This association was similar for children born by either elective or emergency caesarean section.

But what does it mean?

The temptation with findings like this is to draw a causal link between one factor (caesarean section) and the other (autism or ADHD). Unlike so many other areas of science, the conclusions are easily understood and the implications appear obvious.

But the simplicity is deceptive, and says more about our desire for simple answers than it does about the truth of the science.

The studies included in this meta-analysis used a branch of science called epidemiology, which is concerned with how often conditions and diseases occur in different groups of people and why, and how to prevent or manage them.


Read more: Epidemiology and the media


Epidemiological studies survey a large population and find a pattern of results that indicate a certain factor may be coinciding with a certain disease more often than we would expect by chance.

In this case, there is the observation that people with autism or ADHD are more likely to be born by caesarean section than we would otherwise typically expect.

But this kind of epidemiological study is unable determine if one factor (caesarean section) causes another (ADHD or autism).

There are two key reasons why.

First, we can’t rule out that a third factor may be influencing this association. We know, for example, that caesarean sections are more common for pregnant women who are obese and older, and who have a history of immune conditions such as asthma.

All of these factors have also been linked with an increased chance of having a child with autism, and it is entirely possible – and some would argue, probable – that it is more likely these factors underlie the relationship between caesarean section and neurodevelopmental disorders.

The link might be due to other factors such as the mother’s age or weight. Christian Bowen

The second reason is that these kind of epidemiological studies are unable to provide what scientists call “a mechanism” – that is, a biological explanation as to why this association may exist.

A mechanism study in this area may be to explore biological differences in newborns either born via vaginal or caesarean delivery, and understand how these differences may lead to atypical behavioural development.

Without a strong body of evidence from these kinds of studies, there is simply no scientific basis for concluding a causal link between caesarean section and neurodevelopmental disorders.

So what should we take away from this study?

The study provides a strong basis for concluding there is a statistical association between caesarean section delivery on one hand, and autism and ADHD on the other. But that’s about it.

Why this link exists remains unknown, but it is almost certain that a caesarean delivery alone does not contribute to the odds of a child developing autism or ADHD.

Instead, it is likely that other pregnancy factors play a role in this relationship, as well as genetic factors that may interact with the environmental influences during pregnancy to contribute to brain development.


Read more: ADHD prescriptions are going up, but that doesn’t mean we’re over-medicating

Should I take Fish oil supplemen

Although the evidence for the heart benefit is not clear, the reason I recommend fish oil supplement is for the joint (arthritis) and brain benefits. Any heart benefits are a bonus. I take 12 grams fish oil daily (6 capsules am, 6 caps pm.)

Despite new findings, the jury is still out on whether omega-3 supplements reduce heart attacks

November 15, 2018 6.01am AEDT Omega-3s reduce the risk of blood clots and are anti-inflammatory. from shutterstock.com

Author

  1. Garry Jennings Professor of Medicine, University of Sydney

Disclosure statement

Garry Jennings receives funding from the National Health and Medical Research Council.He is affiliated with the National Heart Foundation, Sydney Health Partners (University of Sydney) and Baker Heart & Diabetes Institute..

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A recent widely-reported study has reignited debate around whether omega-3 supplements reduce the risk of heart attack and stroke. The study showed a particular form of omega-3 oil lowered the risk of people with heart disease experiencing a major “end point” event by 25%. This end point is one or a combination of several serious issues such as fatal or non-fatal heart attack, stroke, angina (chest pain) and coronary surgery.

The REDUCE-IT trial included more than 8,000 participants and was presented at the American Heart Association Scientific Sessions in Chicago and published in the New England Journal of Medicine. It was the largest randomised controlled trial (where one group is given the intervention tested and another a placebo and the results are compared) performed to-date testing the benefits of omega-3 supplements for heart disease.


Read more: Randomised control trials: what makes them the gold standard in medical research?


But before you buy fish oil supplements from the local pharmacy, there are some things to be aware of. The drug tested, Vascepa, wasn’t a standard over-the-counter fish oil capsule. Vascepa is made from a highly refined component of fish oils (icosapent ethyl) and the participants received a very high dose (4 grams per day). This is far more omega-3 than most people take with fish oil capsules. Vascepa is available on prescription in the US but not everywhere, and not in Australia.

The study participants either had cardiovascular disease and were aged over 45, or were at high risk of cardiovascular disease and aged over 50. Those at risk had diabetes and at least one other risk factor. The results apply best to people with similar characteristics to the study group and cannot necessarily be generalised more broadly.

Nevertheless, it was a pretty good study performed by reputable investigators across 11 countries with convincing results. So, what does this mean for the see-saw of advice offered on whether to take or not to take fish oil supplements to prevent major heart issues?

Not everyone with heart disease would necessarily benefit from the supplements participants received in the trial. from shutterstock.com

A bit of history

In the early 2000s medical authorities were recommending fish oil supplementation for people who had experienced a cardiovascular event such as a heart attack or stroke.

At that time, two large randomised controlled trials reported that eicosapentaenoic acid supplements (which contained EPA and docosahexaenoic acid (DHA)) significantly reduced fatal heart disease. EPA and DHA are the major oils found in fish oil supplements and are called omega-3s.

In 2017 the American Heart Association was more circumspect, noting that the dramatic benefits seen earlier were less evident in subsequent trials. But supplements were still recommended for certain people with heart or vascular disease.

By early 2018, the tide seemed to have turned completely as a widely publicised study concluded there was little evidence for the benefit of fish oil supplements in preventing heart disease. The study was a systematic review, which combined the results of ten trials testing fish oil supplements (at a lower dose than the REDUCE-IT trial), involving 77,917 older adults at high risk of cardiovascular disease.


Read more: Health Check: fish oil, anyone?


So, what are we to believe? A well-conducted randomised controlled trial or a systematic review of all the evidence? An RCT is considered gold standard by guideline committees. A well-done systematic review or meta-analysis is also considered as providing powerful evidence.

So, what’s the verdict?

The trials in the systematic review varied widely in design, dose, patient population, end points and the validity of lumping them all together is questionable. Also, finding no evidence of benefit is not the same as finding no benefit, particularly in some people under certain conditions that may be lost in the overall analysis. Plus, the results are not just a reflection of the treatment under examination but also of the quality of the studies included.

REDUCE-IT was funded by the manufacturer. There is no other way it would have been done and if the results stand up it could save millions of lives, but some will question the veracity of the findings because of the funding source. So, all of this leaves certainty of whether supplements are good for heart health up in the air.

It’s still a fact that cold water fish are good for you. from shutterstock.com

Fortunately (and as far as we know) some “truths” remain. Eating fish is still good for you. The origin of the fish is important, not only to avoid contaminants but also because the omega-3 content and relative amounts of EPA and DHA varies. Cold water, oily fish such as salmon, sardines, mackerel, trout and tuna contain the most.

If you cannot eat fish, there are plant sources of omega-3s found in some nuts and vegetable oils such as canola, chia, flaxseed, and soy. These have not been studied as extensively as those of marine origin.


Read more: How Australians Die: cause #1 – heart diseases and stroke


Omega-3s including over the counter capsules have definite biological effects. They reduce triglycerides (the type of fat that contributes to hardening of the arteries) and the risk of blood clots, and are anti-inflammatory. These changes are mostly seen at higher doses.

The evidence will evolve further but, in the meantime, and based on a recent evidence review, the National Heart Foundation recommendations don’t advise health professionals to routinely recommend omega-3 supplements for heart health. It does advise health professionals consider the use of omega-3 supplements for those with high triglyceride levels and as an additional treatment for heart failure.

And lastly, everyone should include two to three serves of fish per week in their diet.

Menopausal mood swings can signal more serious mental illness

Menopausal mood swings can signal more serious mental illness

Most women expect to experience the effects of hormonal changes when they come to menopause and many anticipate increased irritability and mood swings. But mood swings that can be just an annoyance for some women can develop into something more serious for others.

Menopause usually begins around the age of 50, when the body’s production of oestrogen and progesterone slows. This can leads to a range of effects such as hot flushes, vaginal dryness, breast tenderness and trouble sleeping. These symptoms can last around five years.


Read more: Chemical messengers: how hormones change through menopause


Menopausal hormone fluctuations can have a significant impact on women’s mental health, with some women more vulnerable to these changes than others. These mental health problems require specific treatment and support.

Depression and anxiety

Women are two to four times more likely to have an episode of major depression during menopause than at other times in their lives.

Although some women can have an episode of depression for the first time during menopause, women with a history of recurrent depression are up to 4.5 times more likely to experience another episode of depression at the start of menopause than other women at this stage of life.

Anxiety disorders (generalised anxiety disorder, panic disorder and social anxiety disorder) are the most common of the mental health problems, with around 25% of the population experiencing one in the last 12 months.

But despite anxiety symptoms and panic attacks being commonly reported during menopause, little is known about their link with menopause.

Schizophrenia

Oestrogen has a protective effect against psychotic symptoms for women, due to its modulating effect on the neurotransmitter dopamine.

Excess dopamine is one of the neurological changes seen in patients with schizophrenia, a mental illness that causes episodes of delusions and hallucinations.


Read more: Trick or treat? Alternative therapies for menopause


Women with an existing diagnosis of schizophrenia may be at increased risk of an episode as their production of oestrogen decreases.

While the causes of schizophrenia are a complex mix of genes, your early development and stress, some women develop schizophrenia for the first time after menopause.

Eating disorders

Eating disorders affect women across their lifespan, and often begin at the first major period of hormonal change: puberty.

But researchers are beginning to understand the hormonal changes that occur during menopause also increase the risk of developing an eating disorder, such as anorexia, bulimia and binge eating.

Once again, the increased risk is due to fluctuations in oestrogen, which plays an important role in how we regulate our food intake, affecting feelings of hunger, satiety after eating and weight gain.

Bipolar

Bipolar disorder is a serious mental health disorder affecting up to 2% of Australians. It causes bouts of severe depression and episodes of increased energy, known as mania.

Our research found that women with bipolar disorder may be uniquely affected by menopause in many ways. Disturbances in sleep due to hot flushes, for instance, can affect the onset of depression and mania.

Planning for good mental health

It is important for women with a history of mental health conditions to plan their mental health care when menopause begins.

Women without a history of mental illness should be aware of the risks and talk to their GP prior if they notice persistent changes in mood, or other concerning symptoms.

GPs can prescribe medication and refer to psychologists for Medicare-subsidised counselling, or to psychiatrists for more specialised care.


Read more: A shift in social attitudes can make menopause a positive experience

Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms

BJOG. 2019 Feb;126(3):330-339. doi: 10.1111/1471-0528.15153. Epub 2018 Mar 15.

Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: a systematic review and meta-analysis.

van Driel CM1,2, Stuursma A1,2, Schroevers MJ3, Mourits MJ1, de Bock GH2.

Author information

Abstract

BACKGROUND:

During menopause women experience vasomotor and psychosexual symptoms that cannot entirely be alleviated with hormone replacement therapy (HRT). Besides, HRT is contraindicated after breast cancer.

OBJECTIVES:

To review the evidence on the effectiveness of psychological interventions in reducing symptoms associated with menopause in natural or treatment-induced menopausal women.

SEARCH STRATEGY:

Medline/Pubmed, PsycINFO, EMBASE and AMED were searched until June 2017.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) concerning natural or treatment-induced menopause, investigating mindfulness or (cognitive-)behaviour-based therapy were selected. Main outcomes were frequency of hot flushes, hot flush bother experienced, other menopausal symptoms and sexual functioning.

DATA COLLECTION AND ANALYSIS:

Study selection and data extraction were performed by two independent researchers. A meta-analysis was performed to calculate the standardised mean difference (SMD).

MAIN RESULTS:

Twelve RCTs were included. Short-term (<20 weeks) effects of psychological interventions in comparison to no treatment or control were observed for hot flush bother (SMD -0.54, 95% CI -0.74 to -0.35, P < 0.001, I2  = 18%) and menopausal symptoms (SMD -0.34, 95% CI -0.52 to -0.15, P < 0.001, I2  = 0%). Medium-term (≥20 weeks) effects were observed for hot flush bother (SMD -0.38, 95% CI -0.58 to -0.18, P < 0.001, I2  = 16%). [Correction added on 9 July 2018, after first online publication: there were miscalculations of the mean end point scores for hot flush bother and these have been corrected in the preceding two sentences.] In the subgroup treatment-induced menopause, consisting of exclusively breast cancer populations, as well as in the subgroup natural menopause, hot flush bother was reduced by psychological interventions. Too few studies reported on sexual functioning to perform a meta-analysis.

CONCLUSIONS:

Psychological interventions reduced hot flush bother in the short and medium-term and menopausal symptoms in the short-term. These results are especially relevant for breast cancer survivors in whom HRT is contraindicated. There was a lack of studies reporting on the influence on sexual functioning.

TWEETABLE ABSTRACT:

Systematic review: psychological interventions reduce bother by hot flushes in the short- and medium-term.

© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.