Hormonal Contraceptives and Dermatology

Natalie M. Williams; Michael Randolph; Ali Rajabi-Estarabadi; Jonette Keri; Antonella Tosti

Disclosures

Am J Clin Dermatol. 2021;22(1):69-80. 

In This Article

Acne

Acne is a multifactorial condition caused by inflammation of pilosebaceous units and follicular plugging, with resultant comedones. The exact pathogenesis is not fully understood but involves androgen-induced sebum production, hyperkeratinization, inflammation, and Cutibacterium acnes colonization.[4] Acne is mainly a disease of the young, although adult acne is not uncommon.[5] In adulthood, women are more likely to have acne than men.[6] With the widespread use of hormonal contraception and the high prevalence of acne, understanding the properties of contraceptives and their ability to alter acne is important. By and large, hormonal therapy aims to decrease the sebum-producing effects of androgens, specifically testosterone and dihydrotestosterone.[7] The mainstays of antiandrogenic therapy for acne are spironolactone and COCs.[8]

First-, second-, and third-generation progestins have androgenic properties and therefore theoretically worsen acne. However, when combined with EE, COCs have a net antiandrogenic effect. Estrogen inhibits luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to suppress ovulation and reduce androgen production. COCs also decrease circulating androgens through the increase in SHBG.[9,10] Additionally, they reduce 5α-reductase activity and block androgen receptors.[11] This overall net antiandrogenic effect has allowed COCs to become an important therapeutic option for acne.

COCs have been shown to decrease both inflammatory and non-inflammatory acne.[12] Currently, the FDA has approved four COCs for the treatment of acne (Table 1). However, there are many randomized controlled trials (RCTs) illustrating the efficacy of a variety of COCs. A Cochrane meta-analysis in 2012 reviewed 31 trials with over 12,000 women.[12] Of these trials, 17 compared different COCs with each other, with no consistent differences between the pills. The analysis was unable to determine how COCs compared with alternative acne therapies. Although the Cochrane analysis found few differences between the COCs, a retrospective study of 2147 patients found COCs containing drospirenone to be the most useful for improving acne.[13] Furthermore, a multicenter study in Germany followed 16,781 women taking various COCs with nortestosterone-derived progestins who were switched to CMA/0.03 mg EE.[14] At follow-up after four cycles of CMA/EE, 37% of patients noted improvement in acne severity.

Non-pill forms of hormonal contraceptives have also proven useful in reducing acne. Several case series reported improved acne with the use of contraceptive skin patches.[15,16] Furthermore, one questionnaire-based study demonstrated that 33% of users experienced improvement following initiation.[17] This is likely due to the overall antiandrogenic effect of the patch, as the progestin released has low androgenic properties and reduces the activity of 5α-reductase, causing normalization of skin lipids.[11] Similarly, hormonal vaginal rings tend to reduce acne. On average, vaginal ring users described an improvement in acne, with even fewer reports of worsening acne compared with COCs.[13,18–21]

On the other hand, the remaining non-oral forms of hormonal contraception have a tendency to cause or worsen ace due to their primarily progesterone components. Currently, no RCTs have directly evaluated the effect of hormonal IUDs on acne. A retrospective analysis of 2147 patients found that, on average, hormonal IUDs worsened acne.[13] Additionally, a survey-based study noted significant changes in acne severity with placement of a levonorgestrel-releasing IUD. Of the women surveyed, 35% experienced worsened acne, 4% improved, and 61% had no change.[22] Several other studies reported aggravation of acne as an adverse effect of hormonal IUDs.[23–26] Two large clinical studies of levonorgestrel IUDs reported hormonal adverse effects, including acne, to be among the top three reasons for discontinuation.[27,28] Overall, studies suggest that hormonal IUDs worsen acne; however, further studies are needed to elucidate the true relationship, as no objective acne assessments were used and the placement of IUDs occurred at variable times in relation to the cessation of COCs.

Similarly, contraceptive implants are associated with worsening acne. Acne is one of the most common adverse effects of subdermal implants, with an estimated 3–27% occurrence in clinical trials.[13,29–33] Unsurprisingly, the progesterone-only depot injections also tend to cause acne. Acne has been reported as a minor adverse effect in patients receiving the injection, as is common among other progesterone-only-based contraceptives.[13,34–40]

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