Drospirenone and mood.

I read with interest the article ‘Hormonal contraception and mood disorders’, but, noted that it overlooked the 4 mg drospirenone 24/4 progestogen-only pill (Slinda).1 The article also did not consider the 20 microgram ethinylestradiol/3 mg drospirenone preparation which has an indication for treatment of premenstrual dysphoric disorder.

Perhaps the authors might consider that the benefits shown in their pilot study may be due to a 24/4 preparation (also noted in the studies referenced in reducing pill-free interval) as well as the active ingredient?

The authors of the article comment:

The 4 mg drospirenone preparation became available in Australia in October 2021 after we wrote the article.1a

For contraceptives containing drospirenone, a 2012 Cochrane meta-analysis tentatively described improvement in women with premenstrual dysphoric disorder, however there was a large placebo effect.2a Our clinical experience with the 20 microgram ethinylestradiol/3 mg drospirenone preparation in women with premenstrual dysphoric disorder and (commonly) a trauma history is that the lower dose ethinylestradiol, compared to many other preparations, did not improve premenstrual dysphoric disorder as well as the combination of estradiol and nomegestrol.3a

The estradiol and nomegestrol combination is effective because of its 24/4 regimen. As the proposed aetiology for mood disturbance is related to the cyclical shift in endogenous estrogen, having more estradiol (24 days) is better in terms of equilibrium of both mood and estrogen. Nomegestrol is a better progestogen in terms of neurotransmitter interactions. However, a head-to-head clinical trial of a 21/7 pill compared to 24/4 needs to be done to confirm this.