Premenstrual Dysphoric Disorder (PMDD) – Drug Treatments
The pathogenesis of Premenstrual Dysphoric Disorder (PMDD) is unclear, but evidence suggests a link between PMDD and a physiological sensitivity to normal fluctuations of the menstrual cycle hormones oestrogen and progesterone. Indeed, suppression of ovarian hormones using Gonadotrophin‐releasing hormone agonists (GnRHa) has been shown to improve premenstrual physical and psychological symptoms.
Recent research indicates that women with PMDD may have dysregulation in a specific gene complex, known as ESC/E(Z), which affects the way in which their bodies respond to circulating sex hormones. Research is ongoing to try and understand more about the aetiology of PMDD and to develop novel treatments.
Below is a summary of some of the latest research on the pharmacological treatment of PMDD. Alternative treatments will be covered in a future blog.
Selective serotonin reuptake inhibitors (SSRI)
The psychopharmacological approach to treating PMDD currently recommended by the British Journal of Obstetricians and Gynaecologists is the use of SSRI’s such as fluoxetine and sertraline. The most recent Cochrane review examining the evidence for the effectiveness and safety profile of SSRIs for treating prementsrual syndrome (PMS) was published in 2013. A total of 31 randomised controlled trials were included in this review and it was concluded that SSRIs were more effective than a placebo at reducing the symptoms of PMS when taken either continuously or during the luteal phase of the cycle. However, SSRI treatment was also associated with adverse effects, including nausea and decreased energy. The most widely studied SSRI for PMDD is sertraline, which has been found to be effective.
Various hormonal therapies are also recommended, including oral contraceptive pills, progesterone only drugs, spironolactone and bromocriptine. Combined hormonal pills, in particular Drospirenone/ethinyl estradiol 3 mg/20 μg in a 24/4 day regimen, have been shown to be effective at significantly improving both the physical and psychological symptoms of PMDD. All of the studies supporting the use of spironolactone and bromocriptine in the treatment of PMDD are dated, therefore more research is needed to better understand whether these drugs have a role to play in current best practice.
Other pharmacological treatments showing potential as a possible PMDD treatment include:
A randomised controlled trial published in 2017 indicates that premenstrual treatment with the GABAA modulating steroid antagonist (GAMSA), Sepranolone (UC1010), significantly reduced PMDD symptoms when compared to a placebo (Bixo et al., 2017). A larger scale phase II trial will be required to confirm these findings but this study shows promise for this treatment. The authors note that treatment timing is particularly important to ensure optimal effect. UC1010 exposure should continue through the premenstrual phase up until the start of menstruation. UC1010 was well tolerated by women during the study and no safety concerns were highlighted. In contrast, other treatments such as SSRIs and oral contraceptives are associated with various side-effects.
Administration of dutasteride, a 5α-reductase inhibitor, prevents the conversion of progesterone into its neurosteroid metabolite allopregnanolone. Research has shown that treatment with dutasteride significantly reduces the occurrence of PMDD symptoms, including sadness, irritability, anxiety, bloating and food cravings. While this suggests promise for its use as an intervention for PMDD, dutasteride treatment is associated with a number of additional risks. In particular, it is contraindicated in pregnancy as it leads to decreased production of dihydrotestosterone (DHT), which can inhibit the formation of male foetal genitalia.
If you have experience with any pharmacological treatments for PMDD, please do share with those who are still exploring their options.