Throughout history and across many cultures, changes in mood, thinking and emotional responses have been related to hormone changes in women.
Unfortunately, the connection between hormones and mood have had pejorative connotations such as “she’s crazy because it’s that time of month”.
Over the past ten years there has been more concerted, objective study into the actual impact of reproductive hormones on mental state changes, mainly in women and now also in men.
The Monash Alfred Psychiatry research centre (MAPrc) has conducted clinical trials with positive results when using the hormone estrogen to treat severe psychotic symptoms and depression in women and men.
So the statement should actually be “she is doing well because of her hormones – and maybe we should give it to him….” An interesting twist on the attitudes of the past.
Hormones and the brain
Oestrogen and other gonadal horomes affect the brain and, in particular, the mental state of women. We are now developing a better understanding of the multiple physiological effects of estrogens in the brain.
More recent research has led us to the “estrogen protection” hypothesis. This theory says estrogen has a “protective” effect in women who are vulnerable to developing mental illness.
According to the hypothesis, high estradiol production in young women, and changes in circulating estradiol levels during a woman’s life cycle, may contribute to the sex differences observed in the onset and course of schizophrenia.
Population studies on the sex differences in schizophrenia suggest women present with their first episode on average four to five years later than their male counterparts.
Additionally, life cycle studies have shown that women are more vulnerable for either a first episode or relapse of existing illness at two major periods of hormonal change: during the post-childbirth period (when estrogen concentrations suddenly drop and return to normal levels) and during menopause (when a significant reduction in estrogen levels is observed).
Exacerbation of psychosis has been observed during the low estrogen phases of the menstrual cycle. “PMD” or pre-menstrual depression is also linked to the low estrogen phase of the menstrual cycle.
We are now working on a new hormone treatment for the many women who experience depression in the transition to menopause. Perimenopausal depression is also linked to the decrease of gonadal hormones around the menopause.
We have learnt that estrogens’ protective elements may actually modify the brain chemistry and neural circuits.
Estrogen receptors are mainly located within the hypothalamus (important in oestrogen’s role in sexual and reproductive behaviours), but have recently been identified in many other areas of the brain.
Estrogen impacts on multiple brain chemical systems, including the serotonin, dopamine, and noradrenaline systems – that are all key chemical involved in the development of mental illnesses such as depression, schizophrenia and other disorders.
So it’s not surprising that we’re discovering widespread benefits of administering estrogens to improve depressed mood, alleviate psychotic symptoms and enhance cognition.
We have made promising discoveries in the use of additional hormones to treat psychosis, mania and depressive symptoms, as well as the prevention of cognitive decline.
Wearing a estrogen patch, for instance, can decrease women’s acute psychotic symptoms if used alongside her usual treatment.
Clinical Application
We know estrogen is good for the brain. But hormonal treatments have only been used in a handful of psychiatric studies to date.
This might be because of our ‘silo mentality’ in medicine. Psychiatry often sits outside of developments in mainstream medicine and surgery, and maybe slower in taking up discoveries and findings from other areas.
Hormone treatments are the bread and butter of endocrinology, and to a lesser extent are used in obstetrics and gynaecology. Hormones have not been considered in mainstream psychiatry as a potential treatment until recently.
Women’s health in general is a relatively new specialist field within medicine and probably reflects the standard medical concept that both the typical physician and patient are male.
Women’s mental health as a separate field in medicine is even newer for the same reasons.
Obviously, there are disorders that only affect women such as postnatal depression but there are many reasons to think about the different courses and outcomes for women suffering from common mental illnesses such as depression, bipolar disorder and schizophrenia.
As we move into an era of personalized medicine, the gender of the patient is a very important consideration to tailor treatment towards.
Enter hormone treatment
Our studies show estrogen is effective in decreasing the impact of psychosis symptoms in women. More recently we have shown that adding estrogen to the antipsychotic treatment in men with schizophrenia also improves the outcomes for men, when their blood levels of estrogen rise.
The problem is that there are side effects to using estrogen. In particular, standard estrogen treatment can cause blood clotting disorders and increase the risk of tumours in breasts, ovaries and uterus.
In men, estrogen can lead to feminisation and if used over a long period, can cause sexual dysfunction.
The development of the new, so called ‘brain estrogens’, (or selective estrogen receptor modulators - SERMs) is exciting because it offers the possibility of using estrogen to improve mental health. But it doesn’t have the bodily side effects that standard estradiol (hormone treatments) can.
Future treatments
Psychiatry needs new treatments. Unfortunately there are still large numbers of people who don’t recover from their mental illnesses, despite taking the currently available treatments.
To find new treatments for mental illnesses, we need to really think differently and explore the other fields of medicine, science and the arts. We need to adopt a personalised approach to the treatment of mental disorders, and gender is a key factor.
Hormones may hold an important clue to the understanding and treatment of mental disorders, and this area needs greater exploration.