A Drospirenone Progestogen-Only Birth Control Pill (Slynd) Has Been Introduced in the United States and Europe: Potential Use in Transfeminine Hormone Therapy

By Aly W. | First published December 21, 2019 | Last modified March 8, 2022

A new progestogen-only birth control pill containing 4 mg drospirenone per tablet (brand name Slynd) was introduced for medical use in the United States and Europe a few months ago (Exeltis, 2019; AdisInsight). It’s the first new progestogen-only birth control pill to be introduced in the United States in 45 years (Kaunitz, 2019). Drospirenone was previously only available in combination with an estrogen, specifically at 3 mg with 20 to 30 μg/day ethinylestradiol in combined birth control pills (brand names Yasmin, Yasminelle, Yaz) and at 0.25 to 0.5 mg with 0.5 to 1 mg/day estradiol in menopausal hormone therapy formulations (brand name Angeliq).

Drospirenone is a potent progestogen with an ovulation-inhibiting dose of 2 mg/day in most women and 3 mg/day in all women (Kuhl, 2005; Bastianelli et al., 2018). Ovulation inhibition is a measure of antigonadotropic effect and by extension suppression of testosterone levels. Drospirenone has some antimineralocorticoid activity, some antiandrogenic activity, and no other off-target hormonal actions. This includes no androgenic, estrogenic, glucocorticoid, or antiglucocorticoid activity. Its antiandrogenic activity is about 30% of that of cyproterone acetate. The antimineralocorticoid effect of a 3–4 mg/day dosage of drospirenone is similar to that of 100–200 mg/day oral progesterone or 20–25 mg/day spironolactone (Wiki; Slynd FDA label). The pharmacodynamic profile of drospirenone is advantageous relative to other progestins in that it has no undesirable activity (namely androgenic and glucocorticoid) and is more similar to that of progesterone than almost any other progestin (see here or here for reviews; a few good ones: Sitruk-Ware, 2005; Oelkers, 2005; Rapkin & Winer, 2007; Motivala & Pitt, 2007). Antimineralocorticoid activity in particular is unique to progesterone and drospirenone among progestogens and may provide various health and physical benefits (Wiki).

Due to the introduction of a decently-dosed progestogen-only formulation, drospirenone is a potential option for use as a progestogen in transfeminine hormone therapy. It may be useful not only for its progestogenic effects, but also for its potential application in testosterone suppression. Generally a progestogen dosage of 5- to 10-fold the ovulation-inhibiting dosage is needed to achieve maximal testosterone suppression, and less might be needed in combination with an estrogen (Aly W., 2019). If two of these 4-mg drospirenone tablets were taken per day, that’d be about 3 or 4 times the ovulation-inhibiting dose. It’d likely be a dosage sufficient for considerable suppression of testosterone levels.

The introduction of this new drospirenone-only formulation is particularly notable in the United States, where options for progestogen-only formulations are limited and all of the other available oral progestogen-only formulations aren’t great (Wiki). Medroxyprogesterone acetate (MPA), megestrol acetate (MGA), and norethisterone acetate (NETA) all have undesirable off-target androgenic, estrogenic, and/or glucocorticoid activity (Table), while progesterone has poor oral activity (Aly W., 2018; Wiki). Drospirenone, in contrast, has an excellent pharmacodynamic profile, with little to feel bad about. In this regard, it’s similar to certain other progestogens like natural progesterone, dienogest, nomegestrol acetate (NOMAC), and hydroxyprogesterone caproate (OHPC), which are all progestogens with no known undesirable off-target activity similarly (Table)—although aside from progesterone they also lack the beneficial antimineralocorticoid activity of drospirenone and progesterone.

The main caveat of drospirenone is that since its progestogen-only formulation is a brand new medication, the formulation still has patent protection. Hence, no generic formulations are available or will be available for probably at least a decade. As such, it’s a bit expensive right now; around $250 per month in the United States ($200 with a coupon) (GoodRx). In addition, insurance may not be willing to cover it for transgender hormone therapy, especially at a double or higher dosage. For these reasons, it may be better just to use, e.g., low-dose cyproterone acetate (Aly W., 2019). Nonetheless, it’s nice to see new hormonal medications introduced, especially when decent options are limited.