Depression and cognition in the menopausal transition

Pauline Maki (US) presented the results from a systematic review of scientific literature on depressive disorders in peri- and postmenopausal women. The review was carried out by an 11 member expert panel and convened by the North American Menopause Society (NAMS) and the National Network of Depression Centres (NNDC), American centres of excellence in depression research.

The following are their conclusions:


  1. There is a window of vulnerability in the menopausal transition extending until early post-menopause for the development of depressive symptoms (elevated mood symptoms that do not meet the diagnostic criteria for clinical depression) and clinical depression
  2. The risk of depressive symptoms is elevated during the menopause transition and post menopause, even in women with no history of clinical depression.
  3. Most women who experience a major depressive episode during the menopause transition have a prior episode of depression; therefore, the episode represents recurrence of the illness.

Clinical presentation and diagnosis

  1. Depression during midlife presents with classic depressive symptoms, commonly in combination with menopause-specific syndrome (i.e., vasomotor symptoms, VMS), sleep disturbance) and psychosocial challenges.
  2. Several common symptoms of the menopause transition and postmenopause (hot flashes, night sweats, sleep and sexual disturbance, weight/energy changes, cognitive shifts) complicate, co-occur, and overlap with the presentation of depression during this stage.

Therapeutic effects of antidepressants

  1. Proven therapeutic options for depression (i.e., antidepressants, evidence-based psychotherapies such as cognitive behaviour therapy) should remain as front-line antidepressant treatments for major depressive disorder at any given time in life, including during the menopause transition.

Hormone therapy

  1. There is some evidence that oestrogen therapy has antidepressant effects in perimenopausal women with clinical depression, with or without vasomotor symptoms.
  2. There is also evidence that oestrogen therapy enhances mood and improves well-being in nondepressed perimenopausal and early postmenopausal women.
  3. Hormonal contraceptives, particularly when used continuously, have shown some benefits for mood regulation and could be helpful for women experiencing depressive symptoms while approaching menopause.
  4. Oestrogen therapy is ineffective as a treatment for depressive disorders in postmenopausal women
  5. Most studies on hormone therapy (HT) for the treatment of depression examined the effects of unopposed oestrogen
  6. Oestrogen-based therapies should not be considered as a strategy for prevention in nondepressed, asymptomatic peri- or postmenopausal women.
  7. Oestrogen-based therapies might augment clinical response to antidepressants, including SSRIs and SNRIs, in periomenopausal women with VMS
  8. Oestrogen is not FDA approved to treat depression

Other therapies

The available evidence is insufficient for recommending any of the following or treating depression related to the menopause transition.

  1. Botanical extracts (e.g. St John’s wort, black cohosh, Gingko biloba, ginseng)
  2. Vitamins/Nutritional supplements (folate, omega-3 fatty acids)
  3.  Isoflavones/Phytoestrogens
  4. Neuromodulatory interventions (e.g. transcranial magnetic stimulation)
  5. Other complementary/alternative approaches (e.g. acupuncture, light therapy)

Gaps in knowledge (insufficient data)

  1. Does HT affect cognition in women for whom HT is indicated – i.e. women with moderate to severe VMS?
  2. Does use of HT or oral contraceptives in the perimenopause – as distinct from the early postmenopause – enhance cognition?
  3. Does early use of HT have effects on Alzheimer’s disease risk and the neuropathology underlying risk?
  4. Is HT effective in preventing cognitive decline in women who undergo early surgical menopause?

Although this review found many interesting conclusions, it also identified areas of missing or insufficient data that are in need of research. An area not covered in the research review was that of the gut microbiome and its influence. The gut microbiome is a primary source of neurotransmitters, the stress hormone cortisol seems to impede the development of these neurotransmitters, which could explain why stress can modify the effects of menopausal transition on depression. Infact, one of Pauline's team's current areas of research is measuring the gut microbiome in women that develop perinatal depression compared to women that don’t, so perhaps there will be more on this very soon!