On Boxing Day 1851, Charles Dickens attended the patients’ Christmas dance at St Luke’s Hospital for the Insane. On describing his visit in an article for Household Words, he commented that the experience of the asylum proved that insanity was more prevalent among women than men. Of the 18 759 inmates over the century, 11 162 had been women. He adds: ‘It is well known that female servants are more frequently affected by lunacy than any other class of persons.’

Dickens was as great an observer as any Nobel Prize winner and indeed this passage is one of the very few references in Victorian literature that make the connection between gender and depression, but there are none to my knowledge relating reproductive function to depression. Jane Eyre’s red room and Berthe Mason’s monthly madness in the same novel may be coded examples of this from Charlotte Bronte’s pen. Modern epidemiology confirms that depression is more common in women than men whether we look at hospital admissions, population studies, suicide attempts or the prescription of antidepressants. The challenge remains to determine whether this increase in depression is environmental, reflecting women’s perceived role in contemporary society, or whether it is due to hormonal changes.

It is clear that this excess of depression in women starts at puberty and is no longer present in the sixth and seventh decades. The peaks of depression occur at times of hormonal fluctuation in: (1) the premenstrual phase; (2) the postpartum phase; and (3) the climacteric perimenopausal phase, particularly in the 1 or 2 years before the periods cease. This triad of hormone responsive mood disorders (HRMD) often occur in the same vulnerable woman. The depression of these patients can be usually trreated effectively with estrogens, preferably by the transdermal route and in a moderately high dose. Transdermal estrogen patches of 200 µg h ave been used in our published placebo-controlle d studi es but 100 µg dose is frequently effective.

The 45-year-old, depressed, perimenopausal woman who is still menstruating will often have a history of previous postnatal depression and depression before periods. She will often be in very good mood during pregnancy and also have systemic manifestations of hormonal fluctuation in the form of menstrual headaches or menstrual migraine. Such a woman will often say that she last felt well during her last pregnancy, but then developed postnatal depression for several months. When the periods returned, the depression became cyclical and as she approached the menopause the depression became more constant. The problem with this clear clinical history of a woman who will probably respond to estrogens is that psychatrists believe such patients are ideal for the use of antidepressants. This is because they would recognize that they would have had ‘premorbid history’ of depression and therefore they would have chronic relapsing depressive illness to be treated by psychiatrists. The fact that this depression is postnatal or premenstrual in timing usually escapes them. It is sad that both gynecologists and psychiatrists are products of their own training with too little overlap in knowledge. The patients thus become victims of this professional schism.

The clue to the use of estrogens came with the important and somewhat eccentric paper by Klaiber, who performed the placebocontrolled study of very-high-dose estrogens in patients with chronic relapsing depression. They had various diagnoses and were both premenopausal and postmenopausal. They were given Premarin ® 5 mg daily with an increase in dose of 5 mg each week until a maximum of 30 mg/day was used. There was a huge improvement in depression with these high doses, but this work has not been repeated because of anxiety over high-dose estrogens.

Premenstrual Syndrome (PMS)


Postnatal Depression

Climacteric Depression

Progestogen Intolerance


  1. (1) Estrogen therapy is effective for the treatment of postnatal depression, premenstrual depression and perimenopausal depression — the triad of hormone responsive mood disorders.
  2. (2) Transdermal estradiol 100 or 200 µg patches producing plasma levels of approximately 500 and 800 pmol/1 respectively should be used.
  3. (3) These patients often require plasma levels of more than 600 pmol/1 for efficacy.
  4. (4) Consider adding testosterone for depression, libido and energy.
  5. (5) Patients who still have a uterus require a cyclical progestogen or Mirena ® IUS.
  6. (6) The most effective long-term medical therapy is estradiol patches or an implant of estradiol and testosterone with a Mirena ® IUS in situ.
  7. (7) Ultimately, a hysterectomy plus bilateral salpingo-oophorectomy and implants with testosterone may be requested.
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