By Mayo Clinic staff

Perimenopause, also called the menopausal transition, is the interval in which a woman’s body makes a natural shift from more-or-less regular cycles of ovulation and menstruation toward permanent infertility, or menopause.

Women start perimenopause at different ages. In your 40s, or even as early as your 30s, your may start noticing the signs. Your periods may become irregular — longer, shorter, heavier or lighter, sometimes more and sometimes less than 28 days apart. You may also experience menopause-like symptoms, such as hot flashes, sleep problems and vaginal dryness. Treatments are available to help ease these symptoms.

Once you’ve gone through 12 consecutive months without a menstrual period, you’ve officially reached menopause, and the perimenopause period is over.


By Mayo Clinic staff

During the perimenopausal period some subtle — and some not-so-subtle — changes in your body may occur. Some things you might experience include:

  • Menstrual irregularity. As ovulation becomes more erratic, the intervals between periods may be longer or shorter, your flow may be scanty to profuse, and you may skip some periods. Early perimenopause is defined as a change in your menstrual cycle length of more than seven days. Late perimenopause is characterized by two or more missed periods and an interval of 60 days or more between periods.
  • Hot flashes and sleep problems. About 65 to 75 percent of women experience hot flashes, most commonly during late perimenopause. The intensity, duration and frequency vary. Sleep problems are often due to hot flashes or night sweats, but sometimes sleep becomes erratic even without them.
  • Mood changes. Some women experience mood swings, irritability or increased risk of depression during perimenopause, but the cause of these symptoms may be sleep disruption caused by hot flashes. Mood changes may also be caused by factors not related to the hormonal changes of perimenopause.
  • Vaginal and bladder problems. When estrogen levels diminish, your vaginal tissues may lose lubrication and elasticity, making intercourse painful. Low estrogen levels may also leave you more vulnerable to urinary or vaginal infections. Loss of tissue tone may contribute to urinary incontinence.
  • Decreasing fertility. As ovulation becomes irregular, your ability to conceive decreases. However, as long as you’re having periods, pregnancy remains a possibility. If you wish to avoid pregnancy, use birth control until you’ve had no periods for 12 months.
  • Changes in sexual function. During perimenopause, sexual arousal and desire may change. But for most women who had satisfactory sexual intimacy before menopause, this will continue through perimenopause and beyond.
  • Loss of bone. With declining estrogen levels, you start to lose bone more quickly than you replace it, increasing your risk of osteoporosis.
  • Changing cholesterol levels. Declining estrogen levels may lead to unfavorable changes in your blood cholesterol levels, including an increase in low-density lipoprotein (LDL) cholesterol — the “bad” cholesterol — which contributes to an increased risk of heart disease. At the same time, high-density lipoprotein (HDL) cholesterol — the “good” cholesterol — decreases in many women as they age, which also increases the risk of heart disease.

When to see a doctor
Some women seek medical attention for their perimenopausal symptoms. But others either tolerate the changes or simply don’t experience symptoms severe enough to warrant attention. Because subtle symptoms may come on gradually, you may not realize at first that they’re all connected to the same thing — fluctuating levels of estrogen and progesterone, another key female hormone.

If you do experience symptoms that interfere with your life or well-being, such as hot flashes, mood swings or changes in sexual function that concern you, see your doctor.


By Mayo Clinic staff

As you go through the menopausal transition, your body’s production of estrogen and progesterone fluctuates. These hormonal fluctuations are at the root of the changes your body goes through during perimenopause.

Risk factors

By Mayo Clinic staff

Menopause is a normal phase in a woman’s life. But in some women, it may occur earlier than in others. Although not always conclusive, some evidence suggests that certain factors may predispose you to entering perimenopause at an earlier age, including:

  • Smoking. The onset of menopause occurs one to two years earlier in women who smoke, compared with women who don’t smoke.
  • Family history. Women tend to experience menopause around the same age as their mothers and sisters, although the link between family history and age at menopause is still inconclusive.
  • Never having delivered a baby. Some studies show that never having had a baby may contribute to early menopause.
  • Childhood cancer treatment. Treatment for childhood cancer with chemotherapy or pelvic radiation therapy has been linked to early menopause.
  • Hysterectomy. A hysterectomy that removes your uterus, but not your ovaries, usually doesn’t cause menopause. Although you no longer have periods, your ovaries still produce estrogen. But such an operation may cause menopause to occur earlier than average.


By Mayo Clinic staff

Irregular periods are a hallmark of perimenopause. Most of the time, this is normal and nothing to be concerned about. However, see your doctor if:

  • Bleeding is extremely heavy — you’re changing tampons or pads every hour
  • Bleeding lasts longer than eight days
  • Bleeding occurs between periods
  • Periods regularly occur less than 21 days apart

Signs such as these may indicate the presence of an underlying gynecologic problem that requires diagnosis and treatment.

Preparing for your appointment

By Mayo Clinic staff

You’ll probably start by discussing your symptoms with your primary care provider. If you aren’t already seeing a gynecologist, your doctor may refer you to one.

What you can do
By monitoring your menstrual cycles and recording your signs and symptoms for several months, you’ll gain a better understanding of the changes occurring during perimenopause. You’ll also have valuable information to share with your doctor.

Appointments can be brief. To make the best use of the limited time, plan ahead and make lists of important information, including:

  • A journal of your menstrual cycles for the past few months, including first and last date of bleeding for each cycle, and whether the flow was light, moderate or heavy
  • Detailed descriptions of all your symptoms, including premenstrual symptoms
  • Names and dosages of all medications you take, including nonprescription drugs and supplements
  • Questions for your doctor, such as what treatment options are available

Questions your doctor may ask
To facilitate a discussion about your perimenopausal experience, your doctor may ask questions such as:

  • Do you continue to have menstrual periods? If so, what are they like?
  • What symptoms are you experiencing?
  • How long have you experienced these symptoms?
  • How much distress do your symptoms cause you?
  • What medications or vitamin supplements do you take?

Tests and diagnosis

By Mayo Clinic staff

Perimenopause is a process — a gradual transition. No one test or sign is enough to determine if you’ve entered perimenopause. Your doctor takes many things into consideration, including your age, menstrual history, and what symptoms or body changes you’re experiencing. Some doctors may order tests to check your hormone levels. But other than checking thyroid function, which can affect hormone levels, hormone testing is rarely necessary or useful to evaluate perimenopause.

Treatments and drugs

By Mayo Clinic staff

Possible therapies to treat perimenopausal symptoms include:

  • Oral contraceptives. These are often the most effective treatment to relieve perimenopausal symptoms — even if you don’t need them for birth control. Low-dose pills can regulate periods and reduce hot flashes and vaginal dryness.
  • Progestin therapy. If you have irregular periods, but you can’t — or choose not to — use oral contraceptives, cyclic progestin therapy may regulate your periods. Some women with heavy bleeding during perimenopause may find relief from a progestin-containing intrauterine device (IUD).
  • Endometrial ablation. Endometrial ablation may provide relief from the heavy bleeding some women experience during perimenopause. During the procedure, the lining of the uterus (endometrium) is destroyed using a laser, electrical energy or heat, which effectively reduces menstrual flow or ends menstruation. This procedure isn’t the right choice for everyone, so talk with your doctor about what is best for you.

Lifestyle and home remedies

By Mayo Clinic staff

Making healthy lifestyle choices may help ease some of the symptoms of perimenopause as well as promote good health as you age. These choices include:

  • Good nutrition. Because your risk of osteoporosis and heart disease increases at this time, a healthy diet is more important than ever. Adopt a low-fat, high-fiber diet that’s rich in fruits, vegetables and whole grains. Add calcium-rich foods or take a calcium supplement that also supplies vitamin D, which helps your body absorb calcium and helps protect against bone loss. Avoid alcohol and caffeine, which can trigger hot flashes.
  • Regular exercise. Regular physical activity helps prevent weight gain, improves your sleep, strengthens your bones and elevates your mood. Try to exercise for 30 minutes or more on most days of the week. Combining walking with strength training, for example, has been shown to help prevent bone loss and fractures in women who have gone through menopause.
  • Stress reduction. Practiced regularly, stress-reduction techniques, such as meditation or yoga, can promote relaxation and good health throughout your lifetime, but they may be particularly helpful during the menopausal transition.

Alternative medicine

By Mayo Clinic staff

In addition to conventional therapies, many women transitioning toward menopause want to know more about complementary and alternative approaches to treating their symptoms. Researchers are looking into these therapies, hoping to determine their safety and effectiveness, but evidence is still often lacking. Be sure to tell your doctor about any complementary or alternative therapy you are using or considering. Here are a few options that show some potential for treating menopausal symptoms while still being fairly safe:

  • Black cohosh. This herb extract is used to treat hot flashes and other menopausal symptoms. While various studies show that it does reduce menopause-related symptoms such as hot flashes, design flaws in these studies and variations in the product itself make it difficult to arrive at definite conclusions. Overall, black cohosh appears relatively safe, but avoid it if you have a liver disorder. If you’d like to try it, discuss it with your doctor first.
  • Phytoestrogens. These are plant-derived compounds that have estrogen-like properties. There are two main types of phytoestrogens — isoflavones and lignans. Isoflavone supplements are generally extracted from soy or red clover. They may be helpful for mild hot flashes and have a protective effect on your bone density. They may also help decrease blood pressure and low-density lipoprotein (LDL or “bad”) cholesterol. Lignans are derived mainly from flaxseed. Fewer studies support their use in treating menopausal symptoms, although they also may help improve cholesterol. Be careful using phyotestrogen supplements if you have an increased risk of a disease or condition that’s affected by hormones, such as uterine fibroids, endometriosis, or breast, uterine or ovarian cancer. Also, be cautious if you’re already taking a medication that increases your level of estrogen, such as birth control pills, hormone therapy or tamoxifen.
  • Dehydroepiandrosterone (DHEA). This is a natural steroid that’s produced by your adrenal gland. Some studies show that DHEA supplements help minimize menopausal symptoms such as hot flashes, vaginal atrophy, sexual dysfunction and bone loss. But other studies have found no such evidence, and several studies have reported harmful effects from high doses of DHEA, so more research is needed.

Although study results have been mixed, other complementary therapies with low-risk profiles such as acupuncture, yoga and paced breathing have shown some benefit in improving menopausal symptoms. These therapies may help reduce stress and improve psychological well-being, as well. Talk to your doctor about what complementary and alternative therapies may be helpful to you.


Low mood and depressive symptoms during perimenopause

Perimenopausal women have an increased risk of developing new onset and recurrent mental health conditions such as anxiety, low mood and depressive symptoms. General Practitioners frequently prescribe antidepressants as the first-line treatment for these symptoms, despite clear lack of evidence for their efficacy and their unfavourable side effect profile. This article, written by a General Practitioner, gives a practical overview of the mental health symptoms which women may report to their General Practitioners during the menopausal transition and discusses underlying causes, assessment, risk factors and treatment options based on current evidence.

The perimenopause is defined as the transitional period prior to menopause and features clinical, biological and endocrinological changes. The perimenopause ends 12 months after the last menstrual period.1 The median age of onset of perimenopausal symptoms is 47.5 years.2 The average duration of the menopause transition is four years (defined by menstrual cycle irregularity), but the individual variation for this phase ranges from 0–11 years.3

The risk of depression increases during the menopause transition.4 In my own clinical practice as a General Practitioner (GP), I find that from the age of 40 onwards, even while periods are still regular, women may experience a variety of different mental health symptoms. These symptoms may be new and out of character, or they may be recurrent, or cyclical, such as exacerbated perimenstrual syndrome (PMS). Heightened anxiety, tearfulness, loss of confidence, low mood or mood swings are common symptoms perimenopausal women report in my day-to-day practice. Many women report that they don’t feel continuously depressed as such, but that they ‘just don’t feel like themselves anymore and don’t recognise the person they have become’. These mental health symptoms during the menopausal transition may occur with or without vasomotor symptoms (VMS). In the absence of VMS, irregular or missed periods, or in women deemed ‘too young’ for being menopausal, health care practitioners often don’t consider hormonal changes as a causative factor and this can affect the treatment options offered to these patients.

There is evidence that episodes of depression associated with reproductive events are triggered by hormonal fluctuations. Some authors have argued that hormone modulated reproductive affective disorders such as PMS, perimenstrual dysphoric disorder (PMDD), pre/postnatal depression and climacteric depression are distinct forms of depression and could be categorised as subtypes of Reproductive Depression.5,6 The term ‘Reproductive Depression’ was first introduced by Nappi et al.,7 and it implies that whilst symptoms may be similar, the underlying biological mechanisms differ from other forms of depression. The term helps to acknowledge that there are types of depression which are specifically linked to the biology of the female sex and this could lead to a more individualised approach to treatment. Currently, the term ‘Reproductive Depression’ is not yet widely acknowledged by the medical profession and it is not included in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) 5 or International Classification of Disease, Eleventh Revision (ICD-11).

Supporting the position that perimenopausal depression is a subtype of reproductive depression has important clinical implications for the treatment and/or prevention of perimenopausal depression.

Hormone replacement therapy (HRT) can be an effective and safe treatment for low mood that arises as a result of the menopause,810 but a recent survey has shown that more than half of the GPs questioned prescribed antidepressants instead of HRT for the management of mood-related menopausal symptoms,11 even though the NICE guidelines state that HRT and/or cognitive behavioural therapy (CBT) can be considered for low mood symptoms related to the menopause.12 The incorrectly interpreted Women’s Health Initiate Study (WHI) from 2002 may still be to blame for the reluctance of some health care practitioners to prescribe HRT.13 A Canadian Study from 2005, which looked at changes in prescribing patterns related to HRT/antidepressants in Canada, confirmed that a significant decrease in the number of HRT prescriptions after 2002 was associated with a statistically significant increase in prescriptions for selective serotonin reuptake inhibitors (SSRIs) during the years after the WHI was published. They concluded that women who were previously prescribed HRT to control their (physical and psychological) menopausal symptoms were now given SSRIs instead.14

Mental health-related symptoms during the perimenopause and the early menopausal years are common and particularly these symptoms and not necessarily VMS can be the main reason why women seek help from their GP. Epidemiological studies have shown that between 45% and 68% of perimenopausal women report elevated depressive symptoms.15 In 15%–30% of perimenopausal women, symptoms are severe enough to be regarded as a depressive disorder.16

It is important that GPs have an awareness about these symptoms (Table 1) and their possible underlying causes in women in this age group. Every woman will experience this time in her life differently and every woman has a different range and severity of symptoms at a different age, before her periods stop for more than 12 months and she is postmenopausal. From my own experience as a menopause care provider, I find that women from their early 40s onwards frequently report that they feel more anxious, irritable and insecure, that they feel easily irritated, angry and that there are times when they feel like they are losing control over their life. Some women say that they feel overall less confident, less resilient to stress and that they have become indecisive and insecure for no reason. These symptoms often come and go during the day or they can last continuously for extended periods of time. Frequently, women also report that symptoms are exacerbated during the days before their period start. Depending on the severity and frequency of these symptoms, they can have a major detrimental effect on the way women function at work, on their relationship with their partner and on their family.


Table 1. Mental health symptoms women report during the perimenopause.1719

Table 1. Mental health symptoms women report during the perimenopause.1719

Animal studies have shown that ovarian steroids have a direct impact on neurotransmitter system activities, including regulation of metabolic enzyme production as well as receptor and transporter protein activity. The pattern of effects of ovarian steroids on the serotonin system in humans is similar to those observed in animals. There is also evidence that reproductive steroids influence the serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis.3 Neurobiological evidence indicates that estradiol has neuromodulary and neuroprotective effects in the hypothalamus, amygdala and the hippocampi, which are directly relevant to mood symptomatology. Estrogen acts as a serotonergic agonist and is implicated in multiple mood regulating mechanisms in different brain regions. It increases serotonergic postsynaptic responsivity, increases the number of serotonergic receptors and enhances serotonergic transport and uptake.20 A clinical study from 2015 demonstrated that the sudden (blinded) withdrawal of estradiol, which was given to participating perimenopausal women as a transdermal patch, precipitated depressive symptoms in those women who had a history of perimenopausal depression. The women in the control group, who also had a history of perimenopausal depression, but who continued to receive estradiol, had no recurrence of their depressive symptoms. The depression inducing effects of estradiol withdrawal in this study only affected women with a history of perimenopausal depression, which suggests that perimenopausal changes in estradiol levels can trigger depression in a susceptible subgroup of women.21 Results from another clinical trial suggest that estradiol variability in the menopause transition enhances emotional sensitivity to psychosocial stress and this increased sensitivity may contribute to the development of depressed mood. These effects of estradiol fluctuation on stress sensitivity and mood appear to be independent of estradiol levels and VMS.22 There is substantial evidence now that fluctuations of estradiol levels during the menopause transition trigger alterations in the HPA axis and changes in cortisol levels, which further supports the idea that perimenopausal depression is unique in its aetiology and that affected women could benefit from interventions to stabilize estradiol levels, such as HRT.23,24

There are risk factors which make a subgroup of women more vulnerable to developing depressive symptoms during the perimenopause (Table 2). Women who have a history of increased sensitivity to hormonal fluctuations and to reproductive endocrine changes, such as PMS/PMDD or postnatal depression (PD), but also women with a history of oral contraceptive-induced dysphoria have a higher risk of developing depressive symptoms during the perimenopausal years.3 Perimenopausal women with a history of PMS are three times more likely to report symptoms of depression during the menopausal transition compared to premenopausal women.17 But even in women with no history of depression, the risk of new onset depression during the perimenopausal years is still twice as high as in premenopausal women.3


Table 2. Factors which increase the risk for depressive symptoms during the perimenopause.25,26

Table 2. Factors which increase the risk for depressive symptoms during the perimenopause.25,26

GPs have usually 10 min to take a history, make a diagnosis and discuss treatment options. It is not realistic to carry out a thorough mental health assessment during 10 min and often it requires several visits to enable the GP to make a diagnosis and for women to make an informed decision about the best possible treatment option. Blood tests such as FSH levels may be considered in symptomatic women aged 40–45 and of course if premature ovarian insufficiency is suspected in women below the age of 40.27 The GP should ask the patient about a history of depression including PD, PMS/PMDD, quality of sleep, periods (flooding, pain, frequency), contraception, as well as VMS (hot flushes, night sweats). Validated instruments such as the beck depression inventory, Hamilton Depression Rating Scale or the Patient Health Questionnaire-9 can be used to measure and monitor the severity of depressive symptoms. The Greene Climacteric Scale is a specific assessment tool for menopausal symptoms, which includes physical as well as psychological parameters.28 Another useful tool is the Meno-D questionnaire. This is a relatively new rating scale (2018), which was specifically developed and validated to assess the rate and severity of the characteristic symptoms of perimenopausal depression (Table 3). The concept of the Meno-D scale is based on a five-factor model: self; somatic; cognitive; sleep; sexual. It is designed to be used by clinicians, researchers and as a self-assessment tool for perimenopausal women. The questionnaire asks 12 questions and each question has five answer options, each graded from 0 to 4, according to severity.19 Unfortunately, the paper does not provide scoring thresholds which would help to practically define normal from abnormal results. It may therefore be more useful as a symptom monitoring tool rather than a diagnostic tool.


Table 3. Clinical areas which are assessed by the Meno-D questionnaire.19

Table 3. Clinical areas which are assessed by the Meno-D questionnaire.19

Untreated depressive symptoms greatly affect the quality of life, relationships and the ability to function in the workplace. Depression is associated with an increased risk of heart disease, diabetes, osteoporosis and in the worst case, suicide.16 Treatment should be personalised and tailored to each individual woman and her needs. Treatment progress needs to be monitored, and women should be reviewed frequently. A careful risk assessment and history taking prior to starting treatment is essential. Personal health beliefs, ideas, concern and expectations should be considered, and doctors should work in partnership with the patient, giving relevant evidence-based information to help women to make an informed decision about the best treatment option. Advice about healthy lifestyle measures like smoking cessation, reducing alcohol intake, healthy eating, exercise and managing stress should be included during the discussion about treatment. CBT and mindfulness-based therapies can be offered in addition to medication depending on severity and preferences.29

Hormone replacement therapy

Fluctuating estradiol levels have been shown to contribute to the development of depressive symptoms and low mood during the perimenopause. Stabilising estradiol levels with HRT has been shown to be an effective treatment for mild to moderate depressive symptoms.9,30,31 One recent clinical study showed that the combination of transdermal estradiol in combination with micronized progesterone helped to prevent clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women.8

The NICE guidelines state that HRT should be considered as a treatment for low mood that arises as a result of the menopause. The guidelines also state, that due to lack of evidence, SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) are not recommended to treat low mood in menopausal women who have not been diagnosed with clinical depression.12 It is important that health care professionals who are involved in the care of menopausal women are mindful to distinguish between severe major depressive episodes and less severe depressive symptoms and low mood. Women who diagnostically fulfil the criteria for major depression and clinical depression should still be treated with antidepressants as the first-line treatment.

Beyond the stabilisation of estradiol fluctuations to treat low mood, HRT is also the first choice for the treatment of VSM in woman who don’t have contraindications. HRT improves overall quality of life, energy levels and sleep and it does not negatively affect libido or cause sexual dysfunction.32 In addition, HRT is licenced for the prevention and treatment of osteoporosis,32,33 and can help to prevent cardiovascular disease if started early enough.34 HRT, preferably transdermal estradiol (gel or patch) should be offered as the first-line treatment to women with mild perimenopausal depressive symptoms.35 Women with a uterus need endometrial protection when using estrogen replacement; however, many women with a history of PMS/PMDD and oral contraceptive-induced dysphoria are sensitive or even intolerant to synthetic progestins. Micronized progesterone (orally or vaginally) given continuously or cyclically or the Mirena coil (IUS) have been shown to be better tolerated than other progestogens with regard to mood-related side effects.36


In a large metanalysis, antidepressants have been shown to be more efficacious than placebo in adults with major depressive disorder, but this analysis did not specifically look at perimenopausal women.37 In 2018, the North American Menopause Society (NAMS) issued a consensus statement about the evaluation and treatment of perimenopausal depression. These guidelines recommend that antidepressants, CBT and other psychotherapies should remain the front-line treatments for major depressive episodes during the perimenopause, despite also stating that there is evidence that estrogen therapy has antidepressant effects of similar magnitude to that observed with classic antidepressant agents when administered to depressed perimenopausal woman with or without concomitant VMS.15 The NAMS statement does not provide a treatment recommendation for less severe menopause-related depressive symptoms or low mood, but focuses on major depressive episodes. The NICE menopause guideline on the other hand does make this recommendation by stating that there is no clear evidence for SSRIs or SNRIs to ease low mood in menopausal women who have not been diagnosed with clinical depression.12

With regard to the best choice of antidepressant, only Desvenlafaxine has been studied in two large randomised placebo controlled trials and proven efficacious in the treatment of depressed perimenopausal women. Most other antidepressants have been trialled in cohorts of younger premenopausal or older postmenopausal women.38,39 Clinical trials have shown that compared to placebo, antidepressants can help to reduce the frequency of VMS40,41; however, compared to HRT they are much less effective. HRT has been shown to reduce the severity and frequency of VMS by up to 83%, whereas antidepressants reduced the severity by up to 50%.42 In addition to that, only Paroxetine 7.5 mg (Brisdelle) has so far been approved by the FDA for the treatment of VMS, no other antidepressant is licenced for this purpose.43

Another very important consideration with regard to prescribing antidepressants in perimenopausal women is the unfavourable side effect profile. While HRT is licenced for the prevention and treatment of osteoporosis, SSRIs have been shown to significantly increase fracture risk in perimenopausal women if taken longer than five years.42 Menopausal symptoms can last much longer than five years and the long-term use of antidepressants can further add to an already increased risk of osteoporosis in women. In addition to an increased fracture risk, antidepressants are also associated with cardiovascular side effects, gastrointestinal side effects, increased risk of suicidal behaviour during the first weeks of treatment, weight gain, headache and insomnia.45 More than 50% of women who take SSRIs will experience sexual dysfunction, including low libido, anorgasmia and decreased arousal, which greatly affects quality of life.46

HRT in combination with antidepressants

What needs to be taken into consideration, is the range of severity of perimenopausal mental health symptoms from mild to moderate and severe which is different for each woman. The most severe symptoms may fulfil the criteria of a major depressive episode as diagnosed according to the DSM 5 criteria.47 Women are two to four times more likely to experience major depression during the perimenopausal or early postmenopausal phase.48 Women who fulfil the criteria for major depression should be offered antidepressants as the first-line treatment. In addition, they can be offered HRT if they also experience other menopause-related symptoms. In women with mild to moderate low mood who don’t achieve sufficient symptom control on HRT alone, antidepressants can be an important adjunct medication and there is some evidence that HRT can augment and enhance the efficacy of some antidepressants. HRT can be added to an antidepressant and vice versa.15,17,46 In women with a history of several depressive episodes, who have been stable for many years while taking antidepressants (SSRIs) and who are experiencing a worsening of depressive symptoms together with VMS, the antidepressant dosing may need to be adjusted and add-on hormone therapy should be considered.42 Clinical decisions about treatment should be made on a personalised case-by-case evaluation.

A growing body of research provides evidence that perimenopausal depression is a subtype of Reproductive Depression. Women with a history of depression or hormone-related mood changes seem to be particularly sensitive to perimenopausal estradiol fluctuations and have a higher risk of developing anxiety and depression. It is important that GPs have an awareness of Reproductive Depression and support women who enter and go through the menopausal transition appropriately and effectively. A thorough history of the woman’s mental health, which also includes questions about the menstrual cycle, PMS, PD and side effects to hormonal contraception should be taken. Women should be given relevant information about the benefits and side effects of HRT, as well as antidepressants, so that they can make an informed decision about the best treatment option. Those women who do not have contraindications, such as breast cancer and are not diagnosed with clinical depression, should be offered HRT as the first-line treatment for low mood during the perimenopause and GPs who practice in the UK should follow the NICE guidelines. In more severe cases, such as major depressive episodes, a combination of antidepressants and adjunct HRT should be considered.


The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Not applicable.

ML is the sole author of this work.

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Chaste tree (Vitex agnus-castus)–pharmacology and clinical indications.


Department of Clinical and Experimental Endocrinology, University of Göttingen, Germany.


Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.

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