Hormonal Contraceptives and Dermatology

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

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

Abstract and Introduction

Abstract

Hormones play a significant role in normal skin physiology and many dermatologic conditions. As contraceptives and hormonal therapies continue to advance and increase in popularity, it is important for dermatologists to understand their mechanisms and dermatologic effects given the intricate interplay between hormones and the skin. This article reviews the dermatologic effects, both adverse and beneficial, of combined oral contraceptives (COCs), hormonal intrauterine devices (IUDs), implants, injections, and vaginal rings. Overall, the literature suggests that progesterone-only methods, such as implants and hormonal IUDs, tend to trigger or worsen many conditions, including acne, hirsutism, alopecia, and even rosacea. Therefore, it is worthwhile to obtain detailed medication and contraceptive histories on patients with these conditions. There is sufficient evidence that hormonal contraceptives, particularly COCs and vaginal rings, may effectively treat acne and hirsutism. While there are less data to support the role of hormonal contraceptives in other dermatologic disorders, they demonstrate potential in improving androgenetic alopecia and hidradenitis suppurativa.

Introduction

Hormonal contraception is the most common form of female birth control. It acts through the manipulation of hormone levels, largely progesterone and estrogen. When used as prescribed, hormonal contraceptives may act by halting ovulation, blocking the implantation of fertilized eggs, and/or increasing cervical mucus secretion. Numerous types of hormonal contraceptives exist, including combined oral contraceptive (COC) pills, intrauterine devices (IUDs), implants, skin patches, injections, and vaginal rings.

The dermatologic effects of hormonal contraceptives are due to their capacity to affect androgen receptors through progestins, as well as estrogen receptors through mestranol or ethinylestradiol (EE).^[1] COC pills are divided into four generations, each with varying androgenic potencies. First-generation pills contain progestins derived from norethindrone and have relatively high androgenic activities. The estrogen component of first-generation pills is mestranol, or ethinylestradiol 3-methyl ether. Second-generation progestins include norgestrel and levonorgestrel, which are even more potent in terms of androgenicity. Since the creation of second-generation pills, the estrogen component has been EE. The third-generation progestins, including desogestrel and gestodene, are less androgenic than earlier compounds, which is reflected by increases in sex hormone binding globulin (SHBG). Finally, the only fourth-generation progestin available in the United States (US) is drospirenone, an antiandrogenic compound derived from 17α-spironolactone. Other antiandrogenic fourth-generations compounds include cyproterone acetate (CPA) and chlormadinone acetate (CMA), however they are not US FDA-approved for contraception in the US.^[2,3]

While COCs are the most recognized and developed forms of hormonal contraception, there are also non-pill options. IUDs are effective long-acting contraceptives with rising popularity in recent years. Hormonal IUDs function by releasing levonorgestrel into the uterus with minimal systemic absorption. Subdermal implants (e.g. etonogestrel implant or Nexplanon®, Merck & Co., Inc., Kenilworth, NJ, USA) release the progestin etonogestrel into the bloodstream and can provide highly effective and reversible contraception for up to 5 years. The contraceptive injection (e.g. Depo-Provera®, Pfizer Inc, New York, NY, USA; or depot medroxyprogesterone acetate) also releases progestogen into the bloodstream and is repeated every 3 months, whereas the transdermal contraceptive patch releases both EE and norelgestromin and is applied weekly. Finally, combined hormonal contraceptive vaginal rings include the etonogestrel/EE ring (e.g. NuvaRing ®, Merck & Co., Inc.) and the segesterone acetate/EE ring (e.g. Annovera ®, TherapeuticsMD, Inc., Boca Raton, FL, USA), which are generally worn for 3 weeks and removed for 1 week. While hormonal contraceptives are generally reliable at preventing pregnancy, the various forms are not equal in efficacy. The choice largely depends on patient preference and weighing the adverse and desired effects of each method. In this literature review, we examine the dermatologic effects, both adverse and beneficial, of these hormonal contraceptives.

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Table 1. Effect of hormonal contraceptives on acne
Contraceptive	Conclusions
Combined oral contraceptive	Improves acne (strong evidence)
	COCs have an overall net antiandrogenic effect due to the combined effects of ethinylestradiol and progestin, with few therapeutic differences between the various COC options [7, 9, 11–13, 130–132]
	The US FDA has approved four COCs for the treatment of acne:
	Ethinylestradiol/drospirenone
	Ethinylestradiol/norgestimate
	Ethinylestradiol/drospirenone/levomefolate
	Ethinylestradiol/norethindrone acetate/ferrous fumarate
Vaginal ring	Improves acne (moderate evidence)
Vaginal ring	On average, vaginal ring users reported an improvement in acne, with even fewer reports of worsening acne than COCs [13, 18–20]
Skin patch	Improves acne (limited evidence)
Skin patch	Reduction in acne reported in 33% of users following patch initiation, and commonly reported in several case series [15–17]
Hormonal IUD	Causes acne (moderate evidence)
Hormonal IUD	No RCTs have directly evaluated IUDs on acne vulgaris. Several studies have noted the worsening of acne lesions and acne is one the most common causes of IUD discontinuation [13, 22–28]
Subdermal implant	Causes acne (moderate evidence)
Subdermal implant	One of the most common adverse events and reasons for discontinuation, with 3–27% of patients reporting acne in clinical trials [13, 29–33]
Depot injection	Causes acne (moderate evidence)
Depot injection	Acne has frequently been reported as a minor adverse effect among users [13, 34–40]

COCs combined oral contraceptives, RCTs randomized controlled trials, IUD intrauterine device

Table 2. Effect of hormonal contraceptives on hirsutism
Contraceptive	Conclusions
Combined oral contraceptive	Improves hirsutism (strong evidence)
Combined oral contraceptive	First-line for premenopausal women not seeking pregnancy [55]. Superior to other monotherapeutic options for hirsutism [44–51], but more effective when used in combination with antiandrogens [54]
Vaginal ring	Improves hirsutism (moderate evidence)
Vaginal ring	Preferred to oral EE/drospirenone for overweight PCOS patients with metabolic risk or moderate insulin resistance that does not require metformin [59]
Hormonal IUD	Causes hirsutism (limited evidence)
Hormonal IUD	Up to 41% of participants may experience upon IUD insertion [22]
Subdermal implant	Causes hirsutism (limited evidence)
Subdermal implant	Few reports of hirsutism as an adverse effect of levonorgestrel implants [27, 41]

EE ethinylestradiol, PCOS polycystic ovary syndrome, IUD intrauterine device

Table 3. Effect of hormonal contraceptives on hair loss
Contraceptive	Conclusions
Combined oral contraceptive	Improves AGA (moderate evidence)
	Androgenic effects of the progesterone component may trigger AGA, but the estrogen component promotes hair growth. Women with AGA taking COCs have significantly decreased hair loss and thinning [85, 86]; however, they are not as successful as with acne and hirsutism [90]
	Causes TE (limited evidence)
	TE has been associated with COC interruption in several case series [67, 76]
Hormonal IUD	Causes AGA (limited evidence)
Hormonal IUD	Estimated cumulative incidence of AGA associated with an LNG-IUD is 0.33% over 1 year [75]
Subdermal implant	Causes AGA (moderate evidence)
Subdermal implant	Reported in 1.1–11.5% of patients with progestin implants and is the third most common reason for requesting removal [70–73]

AGA androgenetic alopecia, COCs combined oral contraceptives, TE telogen effluvium, LNG-IUD levonorgestrel intrauterine device

Table 4. Effect of hormonal contraceptives on rosacea
Contraceptive	Conclusions
Combined oral contraceptive	Unclear effect on rosacea (very limited evidence)
Combined oral contraceptive	COCs, particularly earlier generations with high estrogen, are reported as exacerbating factors for rosacea, potentially secondary to estrogen potentiation of corticosteroids on skin [99–101]; however, COCs have been effective in managing the papulopustular lesions, particularly in patients with endocrine disorders [105, 106]
Hormonal IUD	Causes rosacea (very limited evidence)
Hormonal IUD	Case reports of rosacea after IUD implantation, with improvement after removal [107]
Vaginal ring	Causes rosacea (limited evidence)
Vaginal ring	Reported as an adverse effect in trials studying combined contraceptive vaginal rings [108]

COCs combined oral contraceptives, IUD intrauterine device

Table 5. Effect of hormonal contraceptives on hidradenitis suppurativa
Contraceptive	Conclusions
Combined oral contraceptive	Improves HS (moderate evidence)
Combined oral contraceptive	While there are a few reports of HS occurring in association with COCs, the majority of evidence suggests improvement in disease [113]. Female HS patients demonstrate clinical improvement to complete clearance on COCs, which may be equivalent or superior to antibiotic therapy [116–118]

HS hidradenitis suppurativa, COCs combined oral contraceptive

Table 6. Effect of hormonal contraceptives on lichen sclerosus
Contraceptive	Conclusions
Combined oral contraceptive	Causes LS (limited evidence)
Combined oral contraceptive	While a negative association between vulvar LS and COCs has been reported, the most compelling evidence demonstrated a 2.53-fold risk of early-onset LS among antiandrogenic COC users [126, 129]