A useful resource for depression is found at

The Effects of depression on the Body

Depression is a mental disorder, but it can affect your physical health and well-being.

Overwhelming Sadness
Cognitive Changes
Weight Problems
Constricted Blood Vessels
Weakened Immune System
Emptiness or Hopelessness
Preoccupation with Death
Aches and Pains
Poor Appetite
Heart Attack Outcome

The Effects of Depression on the Body

We all feel sad or anxious at times. It’s a normal part of life. However, clinical depression does interfere with your ability to function. Depression affects how you feel and can also cause changes throughout your body. Major depression is a serious medical condition that has a dramatic effect on your quality of life.

According to the National Institute of Mental Health, about 6.7 percent of adults in the United States have depression. People with depression often develop other health issues as well. Major depression is also called major depressive illness or clinical depression.

Central Nervous System

Depression can cause a lot of symptoms, many of which are easy to dismiss or ignore. It may be especially difficult to detect in children, who can’t articulate their symptoms, or in older adults, who may blame their symptoms on aging.

Symptoms of depression include overwhelming sadness, grief, and a sense of guilt. People with depression often complain about feeling tired all the time. They also tend to have trouble sleeping. Other symptoms include irritability, anger, and loss of interest in things that used to bring pleasure, including sex. It may be described as a feeling of emptiness or hopelessness. Some people may find it difficult to put these feelings into words. Frequent episodes of crying may be a sign of depression, but not everyone who is depressed cries.

Other symptoms include inability to concentrate, memory problems, and difficulty making decisions. People with depression may have trouble maintaining a normal work schedule or fulfill social obligations.

Some people who are depressed may use alcohol or drugs. They may become reckless or abusive. A depressed person may consciously avoid talking about it or try to mask the problem. People suffering from depression may be preoccupied with thoughts of death or hurting themselves. There’s an increased risk of suicide.

Children get depressed, too. Signs include clinginess, worry, and unwillingness to attend school. Children may be excessively irritable and negative.

Depression can cause headaches, chronic body aches, and pain that may not respond to medication.

Digestive System

Depression can affect the appetite. Some people cope by overeating or binging. This can lead to weight and obesity-related illnesses like type 2 diabetes. Others lose their appetite or fail to eat nutritious food. Eating problems can lead to stomachaches, cramps, constipation, or malnutrition. Symptoms may not improve with medication.

Cardiovascular and Immune Systems

Depression and stress are closely related. Stress hormones speed heart rate and make blood vessels tighten, putting your body in a prolonged state of emergency. Over time, this can lead to heart disease.

According to Harvard Medical School, patients who are depressed when hospitalized for a heart condition are two to five times likelier to have severe chest pain, heart attack, or stroke, in the next year. Recurrence of cardiovascular problems is linked more closely to depression than to smoking, diabetes, high blood pressure, or high cholesterol. Untreated, depression raises the risk of dying after a heart attack. Heart disease is also a trigger for depression.

Depression and stress may have a negative impact on the immune system, making you more vulnerable to infections and diseases.

– See more at:


BioIdentical Hormones for Anxiety by Jeffrey Dach MD

Anxiety_fear_panic_estradiolBioIdentical Hormones
For Anxiety and Depression

by Jeffrey Dach MD

56 year old Susan suffered from anxiety and panic attacks, and had been prescribed  Valium, Effexor and Wellbutrin by her primary care doctor.  The drugs had adverse side effects and didn’t seem to be helping, so she stopped taking them.  After further discussion, she  told me that symptoms started a few years ago when her monthly cycles stopped and with the onset of menopausal hot flashes.  She noticed that the anxiety and panic attack seems to precede an episode of hot flashes.

Left Image: Anxiety, Fear and Panic courtesy of Wikimedia commons

Estrogen Deficiency Causes Anxiety

We sent Susan to the lab for a hormone panel, and sure enough, Susan’s estrogen level was low. Susan’s symptoms were caused by menopausal estrogen deficiency, a finding commonly seen in the post menopausal age group. Symptoms are promptly relieved with bioidentical estradiol applied as a topical cream twice a day.  Additionally, Susan’s tests revealed vitamin and mineral deficiencies which were, no doubt, aggravating the anxiety attacks.

Susan was started on her bioidentical hormone program which included estradiol and progesterone as a balanced topical cream. She was also started on vitamin B12 and Magnesium supplements.  Six weeks later, Susan reported that her anxiety and panic attacks had improved and were almost gone.  She also noticed better sleep and more clarity of mind, and her night sweats and hot flashes had resolved as well.

Anxiety is Associated with Hot Flashes

Dont Panic estradiol Anxiety

A study published in 2005 Menopause reported that anxiety is strongly associated with menopausal hot flashes, and usually precedes the hot flash episode. (13)  Hot flashes are caused by estrogen deficiency, and are treated with bioidentical estradiol, which virtually eliminates them.(15)(16)(17)

above image: dont panic courtesy of wikimedia commons

The Benefits of Bioidentical Estrogen

My previous articles discuss the safety and the importance of bioidentical hormones.

Uzzi Reiss’s new book Natural SuperWoman contains an excellent discussion of bioidentical hormones.  Chapter 4 covers anxiety, panic attacks and relief with bioidentical estrogen.(1)  Numerous articles (see below) summarize the medical literature showing that low estrogen levels cause anxiety and depression in humans and animals.  Estrogen treatment relieves anxiety and depression as well as virtually eliminates the hot flashes.


What is the Mechanism of Action Of Estrogen in Eliminating Anxiety and Depression?

Estrogen receptors have been found in the brain, and estrogen increases the expression of an enzyme in the brain called tryptophan hydroxylase-2 (TPH2).  This enzyme converts tryptophan to serotonin, an important neurotransmitter responsible for an anti-anxiety and calming effect in the brain.  These estrogen receptors have been isolated to specific areas of the brain call the DRN, or the dorsal raphe nuclei (2)(3)(4)(5)(6).

Dorsal Raphe Nuclei Estrogen SerotoninEstrogen Effective for Perimenopausal Depression

A study published in the 2001 Archives of General Psychiatry evaluated bioidentical estrogen as treatment for peri-menopausal depression.  They evaluated fifty women ages 40-55 years, suffering from a depressive disorder and irregular menstrual periods (FSH >25 IU/L).  These women were treated with bioidentical estrogen or placebo over 12-weeks.  Remission of depression was observed in 17 (68%) women treated with bioidentical estradiol compared with only 5 (20%) in the placebo group.  The authors concluded,  “Transdermal estradiol is an effective treatment of depression for perimenopausal women.”(7)

Above left image: Brain Anatomy of DRN: The formatio reticularis of the medulla oblongata, shown by a transverse section passing through the middle of the olive of the midbrain showing (4) DRN Dorsal Raphe Nucleus courtesy of wikimedia commons  4. Raphe.

Estrogen Effective for Post-Partum Depression (after child birth)

Postpartum depression is seen in approximately 13% of women who have recently given birth, and often remains untreated. (10) Various treatments have been tried, including antidepressant drug therapy (SSRI’s), bioidentical estrogen, individual psychotherapy, and group psychotherapy. (10)

Mother and Child By GilmanA study published in the 2001 Journal of Clinical Psychiatry showed that bioidentical estrogen is effective for post-partum depression.(8) Twenty-three women suffering from postpartum depression were recruited from a psychiatric emergency unit.  The women were treated over 8 weeks with bioidentical estradiol (sublingual form).  Baseline serum estradiol levels were very low with a mean of 80 pmol/L, or even lower suggesting ovarian failure. During the first week of estradiol treatment, depressive symptoms resolved rapidly, and serum estradiol levels increased to 340 pmol/L.  By the  second week of treatment, 83% of patients showed clinical recovery.

Left image: Harold Gilman (1876 – 1919). Mother and Child, 1918, oil on canvas. Auckland Art Gallery, courtesy of Wikimedia Commons.

A second earlier study published in 1996 Lancet showed that bioidentical estrogen is an effective treatment for post-partum depression.  Sixty One women suffering from post partum depression were given transdermal estradiol (0.2 mg daily), and rapid improvement was reported during the first month of treatment.(9)

Many women with post-partum depression are treated with SSRI antidepressants which does not address the underlying estrogen deficiency and ovarian failure.  In my opinion,  bioidentical hormone treatment is a more effective and safer treatment alternative.    Bioidentical estrogen has none of the adverse effects associated with SSRI antidepressants which, after all,  may end up in mother’s milk, and may have adverse effects on the breast feeding baby.

Estradiol for Post Partum Psychosis

While post partum estrogen deficiency causes depression in 13%  of patients, a smaller subset go on to develop full blown post partum psychosis. Bioidentical estrogen is also effective for this more severely effected group.  A study done in Finland published in the 2001 Journal of Clinical Psychiatry evaluated 10 women suffering from post partum psychosis.  All had low serum estradiol (mean of 50 pg/ml) indicating gonadal failure.  All were treated with bioidentical estradiol, with serum estradiol levels rising to normal.  Remarkably, estradiol treatment reversed psychiatric symptoms in all patients. (11)

Estradiol  Improves Cognition for Alzheimer’s Dementia

In a study published in 2001 Neurology, twenty postmenopausal women with Alzheimer’s dementia were treated with bioidentical estradiol (0.10 mg per day, topical) and compared to placebo.  Sophisticated neuropsychological tests showed improvement in attention, and in verbal, visual and semantic memory compared with subjects who received a placebo.(12)

Estradiol Reduces Anxiety in Mouse Model

Estradiol in Lab Mice prevents anxietyAlicia A. Walf examined a mouse model in which Estradiol reduces anxiety- and depression-like behavior of aged female mice. Her findings were just published in   Neuroscience Research in Feb 2010.  Matthew N. Hill investigated the mechanism of estradiol as an anxiolytic, and he implicated the enzyme, fatty acid amide hydrolase (FAAH), which  degrades the endocannabinoid anandamide.  FAAH is regulated by estrogen.  Obviously, this is a fertile area for new research, as the exact mechanism has not yet been elucidated


Five supplements that may help with depression

While there’s evidence for the efficacy of some supplements as potential treatments for depression, there’s none for others, and some have been found to be ineffective. Михал Орела/Flickr, CC BY-SA

Over two-thirds of Australians are thought to use complementary medicines ranging from vitamin and mineral supplements to herbal to aromatherapy and homeopathic products. Mental health concerns are one of the reasons why people use supplements, but are they really useful?

While there’s evidence for the efficacy of some supplements as potential treatments for depression, there’s none for others, and some have been found to be ineffective. But effectiveness is not the only concern – the quality and cost of unregulated products can also be problematic.

And then there’s the issue of discerning between bone fide evidence from double-blind randomised controlled trials and slick company marketing campaigns.

Of the supplements that have been studied for improving general mood or treating clinical depression, omega-3 fatty acids, St John’s wort, S-adenosyl-methionine (SAMe), N-acetyl cysteine (NAC) and zinc are the most researched and commonly used.

Omega-3 fatty acids

There are three types of omega-3 fatty involved in human physiology. They are important for normal metabolism.

Epidemiological studies show that low dietary intake of omega-3 oils from fish may be related to increased risk of depressive symptoms. A review of dozens of clinical trials on major depression that assessed the efficacy of these fatty acids alone or in combination with antidepressants, supported their use in depression.

And a meta-analysis combining the results of five similar studies found a significant effect in favour of omega-3 fatty acids for reducing bipolar depression.


S-adenosyl-methionine (SAMe) is a naturally occurring compound found in almost every tissue and fluid in the body that’s involved in processes, such as producing and breaking down brain chemicals including serotonin, melatonin, and dopamine.

Double-blind studies show injected and oral preparations (between 800 milligrams to 1600 milligrams) of SAMe are as effective as antidepressants, and tend to produce relatively fewer adverse effects. SAMe also improves the response to antidepressant medication.

It’s a little expensive but SAMe appears well tolerated with only mild adverse effects such as headaches, restlessness, insomnia and gastrointestinal upsets.

St John’s wort

St John’s wort (Hypericum perforatum) is a flowering plant that has a long history of medicinal use. It’s been studied for treating depression in over 40 clinical trials of varying methodological quality.

A 2008 Cochrane review of 29 trials involving 5,489 patients analysed comparisons of St John’s wort with placebo or dummy pills and with antidepressants. It showed people were significantly more likely to respond to St John’s wort than to placebo. In the same analysis, St John’s wort had an equivalent effect to antidepressants.

Because of the risk of drug interactions, people taking other medicines should only use St John’s wort with low amounts of the plant chemical hyperforin, which has effects on drug levels in the body (see an appropriate health professional for advice on this).

The supplement should not be taken with antidepressants as it can cause serotonin syndrome, a potentially fatal nervous system event.


N-acetyl cysteine (NAC) is an amino acid with strong antioxidant properties that has a history of use in the management of paracetamol overdose. It’s been found to significantly reduce depression in bipolar disorder.

In a 24-week placebo-controlled trial of 75 people with bipolar disorder, one gram of NAC twice a day significantly reduced depression. The supplement appears to have no significant adverse reactions but is currently only available from compounding pharmacies or from overseas.


Zinc is a mineral found in some food, and there’s emerging evidence that it improves depressed mood.

A 2012 review of randomised controlled trials found two 12-week trials, with sample sizes of 60 and 20 people, showed zinc as an adjunct to antidepressants significantly lowered depression.

Zinc can be safely prescribed in doses up to 30 milligrams a day, although it should have amino acid another aid to improve absorption. While zinc is a fairly safe supplement, it may cause nausea on an empty stomach.

A cautionary note

This is a very basic overview of the evidence for these five supplements, and people considering their use should get health professional advice before starting to take them.

The studies mentioned here tend to support that “add-on” prescription of a range of nutrients, such as omega-3 fatty acids, SAMe, folic acid, N-acetyl cysteine and zinc, with various medicines, such as antidepressants, have a beneficial effect in improving treatment beyond that of placebo. But again, be sure to seek medical advice before combining any supplements with medications.

Clinical trials have demonstrated little or no effect for valerian in insomnia, St John’s wort in anxiety disorders or attention deficit hyperactivity disorder, n-acetyl cysteine or docosahexaenoic acid (DHA) fatty acids for unipolar depression, and omega-3 for bipolar mania, among others.

The majority of Australians, especially women, already take a range of nutrient and herbal-based supplements for a number of mental health problems. But, consumers should be mindful of the evidence for their effectiveness and differences between the quality and standardisation of supplements, as well as potential drug interactions.

Click here for information on participating in a clinical trial, running in Brisbane and Melbourne, assessing the use of nutraceuticals for people who are depressed.



Estrogens help depression in many women

Estrogens are more effective in the treatment of depression in premenopausal or perimenopausal women than post- menopausal women. However there is no doubt that depression is helped in postmenopausal women who have been suffering from night sweats, insomnia or vaginal dryness, painful intercourse and marital problems in that most of these problems can be effectively treated and removed. However, it is true that the most impressive effect on mood is seen in younger perimenopausal women in the 2–3 years before the period cease in the menopausal transition. This cannot be diagnosed by blood tests but by a careful history. This depression often occurs in women who are sensitive to abrupt changes in their hormones, either endogenous oestradiol or progesterone. These women had previously had postnatal depression and premenstrual depression in what should be known as reproductive depression. They often also have cyclical headaches/migraines that occur with the cyclical hormonal fluctuations at menstruation. As premenstrual depression becomes worse with age, it blends into the more severe depression of the transition phase and is very effectively treated by moderately high-dose transdermal estrogens used by patches, gels or implants.

– Prof John Studd.


Hormones & Depression in women.

Climacteric. 2011 Dec;14(6):637-42. Epub 2011 Aug 31.

A guide to the treatment of depression in women by estrogens.


London PMS and Menopause Centre, London, UK.


Premenstrual depression, postnatal depression and climacteric depression are related to changes in ovarian hormone levels and can be effectively treated by hormones. It is unfortunate that psychiatrists have not accepted this form of treatment and this paper is an attempt to simplify this treatment, which should include transdermal estrogens, possibly testosterone and, if the woman has a uterus, also progestogen. A balance is often necessary between these three hormones. Transdermal estrogens in the appropriate dose will suppress ovulation and suppress the cyclical hormonal changes that produce premenstrual depression. Estrogens also have a mood-enhancing effect in postnatal depression and the depression in the transitional phase of the menopause. It is possible to add transdermal testosterone which will improve mood, energy and libido. The problem is the progestogen as these women are often progestogen-intolerant. Progestogen should be used in the lowest dose and for the shortest duration necessary to prevent endometrial hyperplasia or the return of premenstrual syndrome-type symptoms if the women are progestogen-intolerant. The use of estrogens for depression in these women does not exclude the use of antidepressants. Hormone-responsive depression cannot be diagnosed by measuring hormone levels but can only be diagnosed by a careful history relating depression to the menstrual cycle, pregnancies and the perimenopausal years. These appropriate questions should prevent the endocrine condition of premenstrual depression being misdiagnosed as bipolar disorder and the woman given inappropriate treatment.

[PubMed – indexed for MEDLINE]

Oestrogen Treatment for Depression in Women – Are Psychiatrists Missing Something?

Abstract. 5th February 2010

There are certain types of depression in women that are effectively treatable with oestrogens, although psychiatrists seem to have closed their minds to this possibility to an extent which becomes dangerous for women. Depression is twice as common in women than men, and occurs at times of hormonal fluctuation. This particularly occurs with premenstrual depression, post natal depression and latterly perimenopausal depression in the menopausal transition. These women are typically very well with a good mood during pregnancy before the post natal depression occurs many weeks after delivery. There are now many randomised controlled trials showing that transdermal oestrogens in a dose of 200 mcgs twice weekly is an effective way of treating this sort of depression that which is best called “reproductive depression”. In patients with a uterus they should have cyclical progestogen for seven days a month or a Mirena coil in order to prevent endometrial pathology and irregular bleeding.

It should be noted that oestrogen responsive depression cannot be diagnosed by measuring hormone levels because they will always be normal for the particular age group but this type of depression should be diagnosed by a careful history taking into account the relationship to the menstrual cycle, to the postnatal period as well as perimenopausal depression as these all tend to occur in the same vulnerable woman. Thus the depressed perimenopausal woman will have a history of recurrent PMS from an early age after the menarche, being in good mood during pregnancy but with post natal depression and later cyclical depression as in PMDD when the periods recur. Unfortunately psychiatrists rarely use oestrogens and will use SSRIs or TCAs which are not only of doubtful long term value, having to be frequently changed, but are associated with serious health problems.

Smoller and colleagues (2009) have shown a 45% increase in stroke, a 32% increase in all cause mortality, a 210% increase in fatal stroke and a 212% increase in haemorrhagic stroke in women taking antidepressants.

Psychiatrists are so misinformed about the details of hormone related depression that it is not rare for young women who have been diagnosed as having bipolar depression by a psychiatrist to be cured completely by the use of transdermal oestrogens. If the same women develop some depression with the cyclical progestogen a hysterectomy with BSO with oestrogen and testosterone replacement will remove the hormonal component of any depression. It is significant that 93% of people with a diagnosis of bipolar depression are women. Many of these have a hormonal component in the causation and need hormonal manipulation of their cycles for a cure.



Climacteric. 2004 Dec;7(4):338-46.

Hormones and depression in women.


Chelsea & Westminster Hospital, London, UK.


The biological plausibility for the effect of sex hormones on the central nervous system is now supported by a considerable amount of clinical data. This critical review guides the reader through the plethora of data, from the earliest reports of menstrual madness in the nineteenth century to neurobiological work in the new millennium. It illustrates through the scientific evidence base that, although the effect of estrogen on the central nervous system, particularly on mood and depression, remains a controversial area, there is now considerable evidence for the psychotherapeutic benefits of estrogens in the triad of hormone-responsive depressive disorders: postnatal depression, premenstrual depression and perimenopausal depression. The article also reviews the compelling data that testosterone supplementation has positive effects for depression, libido and energy, particularly where patients have only partially responded to estrogen therapy.

[PubMed – indexed for MEDLINE]


Coping With Menopause – Depression

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Depression is common in our society, with about 20 per cent of the population likely to experience significant depressive illness at some stage of their life. It may go undiagnosed, and therefore untreated, in many people as they are reluctant to seek help. Women are twice as likely as men to be affected by depression. Depression recurs in up to 80 per cent of people who have one initial depressive illness.

pdf Coping With Menopause – Depression 301.25 Kb

Mood, depression and the menopause

  • Women often report changes in mood around the time of the menopause. Hormonal changes may contribute to moodiness. However moderate to severe depression is not more common at menopause than at other stages of life.
  • There is no direct evidence that menopause causes depression.
  • Mid-life may be characterised by negative thoughts about ageing. Women may feel rejected because there is such an emphasis in Western societies on youth and beauty as desirable feminine qualities, whereas age, wisdom and experience are undervalued.
  • A woman’s experience of ageing depends on her cultural background which includes beliefs, religious views, diet, living conditions, educational level and attitudes to sexuality, reproduction and ageing.
  • In the years leading up to the last menstrual period, women may notice physical and psychological changes. These changes are partly caused by fluctuations in the production of hormones from the ovaries.
  • Women who have suffered from severe psychological premenstrual symptoms (PMS) and significant post-natal depression are at higher risk of depression at menopause.

Symptoms of depression

  • Mood swings.
  • Irritability and anxiety.
  • Lethargy or fatigue.
  • Negative feelings/feeling unloved.
  • Difficulty in coping or making decisions and/or loss of confidence.
  • Sleep disturbance and sleep deprivation.
  • Suicidal thoughts.
  • Sometimes physical symptoms can be associated with depression.

Factors leading to depression

  • Stresses of daily life such as dealing with ageing parents, the death of parents, coping with adolescent children, “empty nest” syndrome, loss of job, unemployment, career change, lack of social support and financial or marital difficulties.
  • Domestic abuse, childhood sexual abuse, and alcohol or drug abuse.
  • Losing the ability to have babies may strongly affect some women. Those who are negative about the menopause, and worry that it is the beginning of old age may become anxious or depressed.
  • Hormonal changes may contribute to moodiness. However moderate to severe depression is not more common at menopause than at other stages of life.
  • Past history of depression and chronic ill-health, or a family history of depressive illness, make menopausal women more likely to develop depression.
  • Low socio-economic status and lack of social support place women more at risk.
  • Women whose menopause is brought on by surgery are also more at risk.

How does depression occur?

Depression is related to hormonal and biochemical changes in the brain. Low oestrogen levels at menopause are associated with lower levels of serotonin, which is a chemical that regulates mood, emotions and sleep. Two other neurotransmitters in particular are implicated in depression. They are noradrenalin and dopamine. So, the hormonal changes at menopause may make women more susceptible to depression. Stress can make this predisposition even worse.

Treatment for depression – lifestyle issues

  • Physical activity and exercise may relieve many of the common physical and emotional symptoms around menopause. Studies show that 30 minutes of moderate exercise five times per week improves the quality and quantity of life
  • Postmenopausal women who exercise have an improved sense of well-being, high self-esteem and self-image. Exercise enhances long-term ability to deal with stress, anxiety and possibly depression, as well as improving sleep.
  • Regular exercise helps women lose fat, and control body weight and appetite over the long term.
  • Recommended exercise for women is at least 30 to 40 minutes of exercise five times a week at moderate intensity.
  • A healthy diet with lots of vegetables, fruits and fibre enhances well-being.
  • Relaxation, meditation and yoga should be incorporated as well as time for oneself. (Refer to the AMS pamphlet on Healthy Aging and Lifestyle)
  • Some women find it helpful to develop a new interest or hobby or may now find time to increase knowledge in an area they always wanted to pursue.
  • Other positive changes can be participation in an activity involving the mind and the body such as music, gardening, religion or dancing.

Treatment for depression – medical

  • Women may benefit from counselling from a professional, such as a family doctor, a psychologist, or a psychiatrist.
  • If menopausal symptoms as well as depression persist, hormone replacement therapy (HRT/HT) may be helpful. Antidepressants are also frequently used.
  • The most commonly used antidepressants are called selective serotonin reuptake inhibitors, or SSRIs.
  • Other drugs with similar action, serotonin/norepinephrine reuptake inhibitors, or SNRIs, may be prescribed. SNRIs influence the action of noradrenaline, another neurotransmitter.
  • Common side-effects of SSRIs and SNRIs include nausea, headache, insomnia, agitation, and changes in sexual feelings.
  • Older types of antidepressants, called collectively the tricyclics, are sometimes prescribed. Side-effects of these include dry mouth, constipation, and effects on memory and concentration.

AMS New directions in women's health 

Note: Medical and scientific information provided and endorsed by the Australasian Menopause Society might not be relevant to a particular person’s circumstances and should always be discussed with that person’s own healthcare provider.

This Information Sheet may contain copyright or otherwise protected material. Reproduction of this Information Sheet by Australasian Menopause Society Members and other health professionals for clinical practice is permissible. Any other use of this information (hardcopy and electronic versions) must be agreed to and approved by the Australasian Menopause Society.

January 2008

Last Updated (Sunday, 14 February 2010 21:20)


Arch Gen Psychiatry. 2006 Apr;63(4):375-82.

Associations of hormones and menopausal status with depressed mood in women with no history of depression.


Department of Obstetrics/Gynecology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.



Whether depressed mood reported in the transition to menopause by women with no history of depression is associated with menopausal status and changes in reproductive hormones is controversial and lacks scientific information.


To identify new onset of depressive symptoms and diagnosed depressive disorders in the menopausal transition and to determine the associations of menopausal status, reproductive hormones, and other risk factors with these cases.


A within-woman, longitudinal (8-year) study to identify risk factors of depressed mood.


A subset of a randomly identified, population-based cohort.


Premenopausal women with no history of depression at cohort enrollment.


The Center for Epidemiological Studies of Depression scale (CES-D) was used to assess depressive symptoms, and the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify clinical diagnoses of depressive disorders.


High CES-D scores (> or=16) were more than 4 times more likely to occur during a woman’s menopausal transition compared with when she was premenopausal (odds ratio, 4.29; 95% confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal status, increased levels of follicle-stimulating hormone and luteinizing hormone, and increased variability of estradiol, follicle-stimulating hormone, and luteinizing hormone around the woman’s own mean levels were each significantly associated with high CES-D scores after adjusting for smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status. A diagnosis of depressive disorder was 2(1/2) times more likely to occur in the menopausal transition compared with when the woman was premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the hormone measures were also significantly associated with this outcome.


Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression.

Comment in


Menopause Int. 2008 Sep;14(3):123-8.

Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates.


Women’s Health Concerns Clinic (WHCC), Department of Psychiatry and Behavioural Neurosciences, McMaster University, James Street South, FB 638, Hamilton, ON L8P 3B6, Canada.


It has long been recognized that women are at a higher risk than men to develop depression and that such risk is particularly associated with reproductive cycle events. Recent long-term, prospective studies have demonstrated that the transition to menopause is associated with higher risk for new onset and recurrent depression. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful life events, past history of depression, body mass index, socioeconomic status and the use of hormones and antidepressants. Accumulated evidence suggests that ovarian hormones modulate serotonin and noradrenaline neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of depressive symptoms during periods of hormonal fluctuation in biologically predisposed subpopulations. Transdermal estradiol and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women. The identification of individuals whom might be at a higher risk for depression during menopausal transition could guide preventive strategies for this population.

[PubMed – indexed for MEDLINE
Menopause Int. 2009 Jun;15(2):76-81.

Depression and the menopause: why antidepressants are not enough?


Center of Gynecology and Medical Sexology, Milan, Italy.



Gender differences, related to varying sexual hormone levels and hormone secretion patterns across the lifespan, contribute to women’s vulnerability to mood disorders and major depression. Women are more prone than men to depression, from puberty onwards, with a specific exposure across the menopausal transition. However, controversy still exists in considering fluctuation/loss of estrogen as a specific aetiologic factor contributing to depression in perimenopause and beyond.


To briefly review the interaction between changes in menopausal hormone levels, mood disorders, associated neuropsychological co-morbidities and ageing, and to evaluate the currently available therapeutic options for perimenopausal mood disorders: (a) treatment of light to moderate mood disorders with hormonal therapy (HT); (b) treatment of major depression with antidepressants; (c) the synergistic effect between HT and antidepressants in treating menopausal depression.


Depression across the menopause has a multifactorial aetiology. Predictive factors include: previous depressive episodes such as premenstrual syndrome and/or postpartum depression; co-morbidity with major menopausal symptoms, especially hot flashes, nocturnal sweating, insomnia; menopause not treated with HT; major existential stress; elevated body mass index; low socioeconomic level and ethnicity. Postmenopausal depression is more severe, has a more insidious course, is more resistant to conventional antidepressants in comparison with premenopausal women and has better outcomes when antidepressants are combined with HT.


The current evidence contributes to a re-reading of the relationship between menopause and depression. The combination of the antidepressant with HT seems to offer the best therapeutic potential in terms of efficacy, rapidity of improvement and consistency of remission in the follow-up.

[PubMed – indexed for MEDLINE]
Maturitas. 2002 Apr 15;41 Suppl 1:S25-46.

The impact of testosterone imbalance on depression and women’s health.


Department of Gynecology and Obstetrics, Gynecological Oncology, University Hospital, Hufelandstrasse 55, D-45122, Essen, Germany.


Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the “baby blues”. It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that “environmental factors” during the time of growing up might be responsible for emotional “up and downs”. T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial interindividual variability in T plasma values exists, making it difficult to utilize them for diagnostic purposes. Therefore a “four-level-hormone classification scheme” was developed identifying when estradiol (E) and T levels are out of balance. (1) Low E-low T levels are correlated with osteoporosis, depression, and obesity; (2) high E-low T with obesity, decreased libido; (3) high T-low E levels with aggression, depression, increased libido, and substance abuse; (4) high E-high T with type II diabetes risk, breast cancer and cardiovascular risk. Testosterone delivery systems are needed where beneficial and negative effects can be balanced. Any woman diagnosed for osteoporosis should be questioned for symptoms of depression.

[PubMed – indexed for MEDLINE]

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