Progestin-only oral contraceptives (often called minipills) are similar in efficacy to combination oral contraceptives containing estrogen and a progestin and are used predominantly by breastfeeding women and in situations where estrogen is poorly tolerated or contraindicated. In 2020, the FDA approved a progestin-only oral contraceptive containing drospirenone (marketed as Slynd). Up until this point, progestin-only oral contraceptives available in the US have all contained norethindrone. Drospirenone (DRSP) is a chemical analogue of spironolactone; it is more likely to suppress ovulation and is less likely to have androgenic side effects (e.g., acne, hair growth) than norethindrone. In addition, for women who experience premenstrual mood changes, drosperinone may also have beneficial effects on mood and is combined with ethinyl estradiol in the oral contraceptive Yaz, which is FDA-approved for the treatment of premenstrual dysphoric disorder (PMDD).
Although progestin-only contraceptives are commonly offered to breastfeeding women at the 6-week postpartum visit, we typically do not recommend the use of the norethindrone-containing minipill in this setting to women at increased risk for postpartum depression–for example, those with a history of PPD or recurrent depression. This recommendation is based on previous studies indicating an increased risk of PPD in women receiving depot formulations of progestogens after delivery. To my knowledge, no studies have investigated the effects of the norethindrone-containing minipill on mood. A recent prospective, non-randomized, open-label study examined the effects of Drospirenone only pill (DOP) 4 mg, in a 24 active/4 placebo regimen, on the mood of postpartum women electing to use a hormonal contraceptive.
Women received counseling on the benefits of progestin-only contraception and its safety during breastfeeding at the childbirth preparation course at 26–34 weeks of pregnancy. Before enrollment into the study, each woman was assessed for mood disorders. Women with moderate or severe depressive symptoms at the postpartum visit were excluded from the study. A total of 71 women received the drospirenone only pill at 2 weeks postpartum, and 78 women in the control group. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at the childbirth preparation course (T0), and at the week 2 (T1), week 12 (T2), and week 24 (T3) postpartum follow-up visits.
In both groups, depressive symptoms increased from T0 to T1. At the T2 follow-up (week 12), EPDS scores had decreased in the group using drospirenone but not in the control group. Similarly, at the T3 follow-up, the score was statistically reduced in the DRSP group but not in the control group.
Encouraging Findings But Further Study Needed
This is the first study to examine the effect of a drospirenone-only contraceptive on postpartum mood. While the women taking drospirenone experienced a decrease in EPDS scores, the control group continued to have elevated EPDS symptoms. The observed decrease in depressive symptoms in women taking drospirenone was statistically significant, but relatively small. While this study is important, it would be premature to conclude that drospirenone decreases the risk of postpartum depression. This study did not indicate the number of women meeting criteria for PPD at follow-up visits. In general, the average EPDS scores were low and would not be consistent with the scores typically measured in women with PPD. Furthermore, the study excluded women with moderate to severe depressive symptoms at week 2.
Nonetheless the findings are promising in that we can continue to explore the use of drospirenone in postpartum women. Drosperinone does not negatively affect breastfeeding, and this study indicates that, at least in women with no or mild depressive symptoms, there is no worsening of postpartum mood symptoms and maybe even some improvement. Effective postpartum contraception is vital, and this study suggests that the drospirenone-only pill might be an acceptable option for many women.
Given the salutary effects of drospirenone on hormonally mediated mood symptoms observed in this study, and in previous studies of PMDD, it will be interesting to see future studies where the drospirenone-only contraception is used in women with increased risk of PPD or in postpartum women who might already have depressive symptoms. In addition, using neuroimaging and other techniques to examine how drospirenone and other progestins affect the female brain may help to refine the treatment of hormonally mediated mood symptoms.
Ruta Nonacs, MD PhD
Caruso S, Caruso G, Bruno MT, Minona P, Di Guardo F, Palumbo M. Effects of Drospirenone only pill contraception on postpartum mood disorders: A prospective, comparative pilot study. Eur J Obstet Gynecol Reprod Biol. 2023 Jul 6; 288:73-77.