Premenstrual dysphoric disorder is just one of the conditions for which women have faced ignorance and scepticism.
At the Senate inquiry into issues related to menopause and perimenopause, AMA president Professor Steve Robson said there was “without doubt an element of misogyny” in the treatment of women’s health.
I would go much further and say that there is systemic misogyny in our healthcare system and it is killing women.
What is medical misogyny?
It is the systemic and pervasive discrimination against women that encompasses research, medical education and equitable access to investigations and treatment.
It is not bad male doctors.
None of us, male or female, were adequately trained that ovarian hormones, estradiol, progesterone and testosterone impact every single aspect of health. And it is still not part of the medical curriculum.
An inevitable result of becoming interested in the impact that perimenopause and menopause have on mental health is seeing how these improperly named sex hormones impact female mental health across the life cycle – recognising the effects that hormonal contraception, the menstrual cycle, pregnancy, and breastfeeding can all have on a woman’s state of mind, or to be more exact, her brain.
Estradiol and progesterone (and testosterone too) have potent effects on the key neurotransmitter circuits: glutamate, GABA, dopamine and serotonin. For the majority of women, it is nothing more than being a bit more irritable or intolerant before their period, but for a group of women their premenstrual symptoms are completely debilitating. This can have devastating and even fatal consequences.
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS) characterised by intense emotional and physical symptoms that occur in the luteal phase of the menstrual cycle (second half), and resolve within a week of menstruation starting. Symptoms significantly impact sufferers’ daily life and functioning.
PMDD affects anywhere between 3-8% of women in their reproductive years, though up to 18% of women almost meet PMDD criteria. The majority of women wait years for diagnosis, and many are misdiagnosed with other mental health conditions such as bipolar disorder or borderline personality disorder.
It is more common in neurodivergent women, women with a history of adverse childhood events (ACEs), complex trauma and there is a genetic element. There is an overlap with eating disorders – women with PMDD are seven times more likely to have bulimia nervosa. It is associated with addiction and criminal behaviour. In severe cases it can cause psychosis.
Premenstrual Disorders Australia (PMDA), the first charity to support PMDD sufferers in the country, was only established in 2022, by lived experience advocate Brie Moore. This is despite studies showing a third of sufferers have attempted suicide – almost the same figure that Dr Katharina Dalton found in her survey of 132 women attending her clinic in University College Hospital, London way back in 1977.
Dr Dalton was an English GP who started her career in 1948, who published the first paper on PMS in 1953. Some suggest her interest in hormones was due to her own PMS, or perhaps she was just astute at recognising patterns of disease. She identified women who had premenstrual exacerbations of other illnesses such as diabetes, migraine, asthma and catamenial epilepsy.
Then her interest evolved to the full syndrome of physical and psychological symptoms women experienced in the premenstrual phase, that she named premenstrual syndrome, or PMS.
Dr Dalton had strict diagnostic criteria for PMS: the symptoms must occur in the premenstrual phase across a minimum of two cycles and resolve after menstruation.
Her treatment centred on the use of diet: three-hourly starch meals to avoid low blood sugar (as the ensuing stress response impacts the ability of progesterone receptors to move progesterone into the cell nucleus) and high-dose progesterone. She recognised that synthetic progestogens (progestins) such as those that are used in hormonal contraception could exacerbate the condition.
Despite establishing the world’s first premenstrual clinic, which ran for 40 years, writing extensively on both PMS and perinatal depression, winning multiple prizes for research and being the first female president of the general practice section of the Royal Society of Medicine, she was met with scepticism and was challenged for her prescribing methods (notably the overprescribing of costly body-identical progesterone).
When assays were developed that could measure hormone levels and it was found that the progesterone levels in women with PMS were no different than those without, her work lost credibility. Or perhaps it was the arrival of a new type of antidepressant, the SSRI.
I wrote a post on Dr Dalton as part of my “Hero Celebrity Doctor” series of social media posts, in response to the current backlash against doctors on social media. These digital opinion leaders use their social media to disseminate research that they have curated and translated, or even written, to both their peers and the general public.
This method overcomes barriers of cost and time, making the latest research available to all. In the menopause space many of these doctors are also connecting, collaborating and supporting each other’s work.
Dr Dalton did not have such easy access to likeminded professionals. And perhaps that is why it took 65 years for PMDD to be officially added to the International Classification of Diseases (ICD) in its 11th revision in 2018.
Professor John Studd developed Dr Dalton’s theory of hormonal mental health and was a strong advocate for using hormones for these women until his death in 2021. He favoured the use of higher dose transdermal estradiol over progesterone alone, to suppress ovulation but maintain natural estradiol levels (unlike a synthetic COCP) and frequently added testosterone too.
What we now know is that PMDD seems to be a disorder of altered sensitivity to sex steroids with an abnormal stress response in the luteal phase. Progesterone’s metabolite allopregnanolone, rather than progesterone itself, seems to be key. It is receptor sensitivity to changing, rather than absolute, levels of hormones, especially of allopregnanolone, perhaps potentiated by lower oestradiol levels in the luteal phase.
This can also explain why PMDD may only first appear in perimenopause when absolute oestradiol levels are often lower.
In the brain, allopregnanolone acts as a positive allosteric modulator at GABA-A receptors with 10 times the potency of benzodiazepines. GABA-A receptors are in the amygdala, hippocampus, and prefrontal cortex – areas which regulate anxiety, aggression and depression. It is postulated that childhood trauma causes dysregulation in the hypothalamic-pituitary-adrenal axis and can cause an increase in the volume of the amygdala.
Interestingly fMRI suggests that allopregnanolone may have a bimodal effect: low oral doses of progesterone, producing low serum concentration of allopregnanolone, increases amygdala reactivity, whereas high doses decrease amygdala reactivity.
This is similar to other GABA-A agonists such as benzodiazepines. Most importantly it could mean that in clinical practice the dose of progesterone in PMDs needs to be higher to avoid “progesterone intolerance”
There are currently no Australian guidelines for treatment of PMDD.
Related
The Royal College of Obstetrics and Gynaecology, UK and the International Association of Premenstrual Disorders (IAPMD) both have guidelines for the treatment of PMDD. Both list various options including transdermal oestradiol with progestogens.
I see many women and girls with PMDD. Many are just part of my normal practice population and have not particularly sought me out. And I wonder if it is on the increase. For some women it appears with their very first period and for others it may only appear in perimenopause. I often see mums and daughters who are experiencing similar mood symptoms at either ends of the reproductive years.
I have been once again really surprised at how effective body identical oestradiol and progesterone can be for many (although not all) of these women. I have had patients find their suicidal thinking disappear within hours of the correct dose of patch being applied, only to recur when a well-meaning colleague suggests they reduce the dose.
But it is rare that PMDD is the only issue. I regularly see women and girls who have PMDD, ADHD, heavy periods and need contraception but may also have migraine with aura.
So my ABC for using hormones in PMDD is below:
PMDD alone
- Transdermal oestradiol (usually requiring higher doses 100mcg patch/4 pumps gel/3 sachets gel) + cyclical progesterone 200mg D17-28
PMDD, young and needs contraception
- Zoely cocp (oestradiol+ nomogestrel)
- Nexstellis cocp (estetrol+ drosperinone)
PMDD + heavy periods + needs contraception
- Slinda(drosperinone) +/- transdermal oestradiol
- Nexstellis cocp
- Mirena + transdermal estradiol +/- progesterone 100mg continuous
The combined contraceptive pill is contraindicated in women with migraine with aura.
Like Professor John Studd, I think testosterone has a role too, but will leave that for another day.
Some women may also need an antidepressant either cyclically or continuously, but maybe that should be second line, after we try treating their hormonal mood disorder with hormones first.
And other women will need much more complex options, especially those who are intolerant of all progestogens, such as medical or surgical menopause with add back hormones.
As always nutrition, exercise, social connection and breathwork are essential and many will need to do prolonged work with a psychologist who is experienced in hormonal mental health and trauma.
Women are not hysterical, but they are fed up. As our new breed of hero celebrity doctors educate the general public with lightning speed it is incumbent upon us as regular practising doctors to keep up too.
And if you want the best bang for buck I would suggest reading up on ovarian hormones. They do a lot more than any of us were ever taught.
Dr Ceri Cashell started her career in general practice in 2004 in Edinburgh but since 2012 she has been working in Avalon, Sydney, where she is a practice principal and owner. She is a passionate advocate for increased awareness of the effects of hormones on physical and mental health.
