Women, hormones and depression
It is clear that this excess of depression in women starts at puberty and is no longer present in the 6th and 7th decade. 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 one or two years before the periods cease. This triad of hormone responsive mood disorders, (HRMD) often occur in the same vulnerable woman.The 45 year old depressed peri-menopausal woman who is still menstruating will often give a history of previous postnatal depression and depression before periods. They 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. She then developed post natal depression for several months. When the periods returned, the depression became cyclical and as she approached the menopause the depression became more constant. Reproductive events also affect the course of bipolar disorder in women. 67% of such women had a history of postpartum depression. Of these, all had episodes of depression after subsequent pregnancies. Subsequently women who were not using hormone replacement therapy were significantly more likely than those who were using HRT to report worsening of the depression symptoms during the perimenopause/menopause. The authors Freeman et al conclude that hormonal fluctuations are associated with increased risk of affective disregulation and mood episodes in women with bipolar disorders.
The depression of these patients can be usually treated effectively by oestrogens, preferably by the transdermal route and in a moderately high dose. Transdermal oestrogen patches of 200 mcgs has been the dose used in published placebo controlled studies but the 100 mcg dose is frequently effective.
The problem with this, (to me), clear clinical history of a woman who will probably respond to oestrogens is that the scientists believe that such patients are ideal for the use of antidepressants. This is because they would recognise that they would have had premorbid history of depression and therefore they would have chronic relapsing depressive illness. The fact that this depression is postnatal or premenstrual in timing escapes this. It is sad that both gynaecologists and psychiatrists are victims and products of their own training with too little overlap in knowledge.
The clue to the use of oestrogens came with the important and somewhat eccentric paper by Klaiber (2) who performed the placebo controlled study of very high dose oestrogens in patients with chronic relapsing depression. They had various diagnoses and were both premenopausal and postmenopausal. They were given Premarin 5 mgs daily with an increase in dose of 5 mg each week until a maximum of 30 mg a day was used. There was a huge improvement in depression on these high doses, (figure 1), but this work has not been repeated because of anxiety over high dose oestrogens.
Premenstrual syndrome
This condition is mentioned in the fourth century BC by Hippocratic but became a medical epidemic in the nineteenth century. Victorian physicians were aware of menstrual madness, hysteria, chlorosis, ovarian mania, as well as the commonplace neurasthenia. In the 1870's Maudsley(3), the most distinguished psychiatrist of the time, wrote "…The monthly activity of the ovaries which marks the advent of puberty in women has a notable effect upon the mind and body; wherefore it may become an important cause of mental and physical derangement…" This and other female maladies were recognised, rightly or wrongly, to be due to the ovaries. As a consequence bilateral oophorectomy - (Battey's operation(4)) - became fashionable, being performed in approximately 150,000 women in North America and Northern Europe in the 30 years from 1870. Longo(5), in his brilliant historical essay on the decline of Battey's operation, posed the question whether it worked or not. Of course they had no knowledge of osteoporosis and the devastation of long-term oestrogen deficiency, therefore, on balance the operation was not helpful as a long-term solution but it probably did, as was claimed, cure the "menstrual/ovarian madness" which would be a quaint Victorian way of labelling severe PMS. The essential logic of this operation was to remove cyclical ovarian function but happily this can now effectively be achieved by simpler medical therapy. Only in 1931 was the phrase 'premenstrual tension' introduced by Frank(6), who described 15 women with the typical symptoms of PMS as we know it. Greene and Dalton extended the definition to 'premenstrual syndrome' in 1953 (7), recognising the wider range of symptoms.Severe premenstrual syndrome (PMS) is a poorly understood collection of cyclical symptoms, which cause considerable psychological and physical distress. The psychological symptoms of depression, loss of energy, irritability, loss of libido and abnormal behaviour as well as the physical symptoms of headaches, breast discomfort and abdominal bloating may occur for up to 14 days each month. There may also be associated menstrual problems, pelvic pain, menstrual headaches and the woman may only enjoy as few as 7 good days per month. It is obvious that the symptoms mentioned can have a significant impact on the day-to-day functioning of women. It is estimated that up to 95% of women have some form of PMS but in about 5% of women of reproductive age they will be affected severely with disruption of their daily activities. Considering these figures it is disturbing that many of the consultations at our specialist PMS clinics start with women saying that for many years they have been told that there are no treatments available and that they should simply "live with it". In addition many commonly used treatments of PMS particularly progesterone or progestogens have been shown by many placebo controlled trials not to be effective. In fact they commonly make the symptoms worse as these read more
