Hormonal Therapies for Acne: A Comprehensive Update for Dermatologists

Abstract

Introduction

Acne impairs quality of life, often leads to permanent scars, and causes psychological distress. This review aims to update dermatologists on the Federal Drug Administration (FDA)-approved and off-label use of combined oral contraceptives (COC), clascoterone, spironolactone, and emerging hormonal therapies for acne treatment.

Methods

We reviewed current literature on hormonal acne treatments and discussed common patient concerns, barriers to care, and individualized care needs.

Results

Different brands and dosings of COC have generally similar efficacy in treating acne. Dermatologists should discuss contraceptive options and provide individualized shared decision-making with patients based on patient preferences, contraceptive needs, comorbidity profile, access, and cost. Spironolactone is an effective acne treatment with clinical trial data to support its use as a first-line acne treatment for women with acne. Potassium monitoring is of low value for patients on spironolactone unless patients have specific risk factors for hyperkalemia. Clascoterone is a safe and effective topical anti-androgen for the treatment of acne in men and women with limited systemic effects on reproductive hormones.

Conclusion

Hormonal therapies are essential strategies to treat acne. Clinicians should expand the use of existing and emerging hormone therapy as part of their acne treatment strategies.

Key Summary Points

Different brands of combined oral contraceptives (COC) have similar efficacy in the treatment of acne and should be considered for patients who desire contraception

Contraceptive choice should be based on shared decision-making considering patient preferences, contraceptive needs, comorbidity profile, access, and cost

Clascoterone is a topical anti-androgen shown to be a safe and effective acne treatment for men and women, though patients may have financial barriers to treatment due to its high cost

Spironolactone is an effective treatment of hormonal acne in women, and routine potassium monitoring has low clinical value except in patients with specific comorbidities

Dermatologists should consider existing and emerging hormonal therapies for the treatment of acne.

Introduction

Acne is a common inflammatory skin disease which affects 9.4% of the global population and may result in permanent scars and psychological distress [1, 2]. Acne worsens health-related quality of life and has the second highest disability burden among skin diseases worldwide [3, 4]. Androgen hormones play a key role in acne development, with prevalence reaching up to 96.0% during adolescence because of changes in androgen levels during puberty [1, 5]. Adults may also experience acne, which disproportionately affects women and individuals on testosterone therapy, with polycystic ovarian syndrome, or with menstrual-related flares [6]. Androgens drive acne development by altering the pilosebaceous unit, resulting in increased sebum production, keratinocyte proliferation, and inflammation [5]. Hormonal therapies treat acne by reducing androgenic activity. This review aims to update dermatologists on the use of hormonal therapies, such as combined oral contraceptives (COC), clascoterone, and spironolactone, to treat acne. This review will also focus on strategies to deliver patient-centered dermatologic care, address common misconceptions, and reduce treatment barriers. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Hormonal Therapies

Combined Oral Contraceptives

COCs contain both estrogen and progestin and are effective in treating acne because of their anti-androgenic properties [7]. The American Academy of Dermatology (AAD) conditionally recommends COC for acne management based on moderate-certainty evidence [8–17]. The Food and Drug Administration (FDA) has approved three COCs—norgestimate/ethinyl estradiol (Ortho Tri-Cyclen^®; Janssen Pharmaceuticals, Inc.), norethindrone/ethinyl estradiol (Estrostep^® Fe; Allergan plc), and drospirenone/ethinyl estradiol (Yaz^®; Bayer HealthCare Pharmaceuticals, Inc.)—to treat moderate-to-severe acne in female adolescents aged 15 and older (14 or older for drospirenone/ethinyl estradiol) who seek oral contraception and have reached menarche [18–20]. Dermatologists may prescribe COC for contraception beyond these three FDA-approved formulations, as similar acne treatment efficacy and safety across different COC formulations was demonstrated in a meta-analysis of 31 clinical trials [21].

Estrogens in COCs typically include ethinyl estradiol (EE), estradiol (E2), or estetrol [22]. Progestins in COCs are progesterone derivatives with pro- or anti-androgenic properties [23]. Progestins are grouped into four generations in the order of decreasing androgenicity: first (norethindrone, ethynodiol diacetate), second (levonorgestrel, norgestrel), third (norgestimate, desogestrel), and fourth (drospirenone, dienogest) [23]. Norgestrel 0.075 mg (Opill^®; Perrigo Co. plc) was recently FDA approved as the first non-prescription daily oral contraceptive and contains both levonorgestrel and inactive dextronorgestrel [24]. Daily oral levonorgestrel 0.030 mg reduced baseline Global Acne Grading System scores by 29.7% in a small 6-month clinical trial of 20 female participants with acne [25].

Patient comorbidity profiles should be assessed through a focused history and physical examination to evaluate the risks and benefits of COC before initiation (Table 1) [26]. COCs have been prescribed safely through telemedicine using self-screening tools that can be adopted in dermatology [27]. COCs are contraindicated in patients with a history of migraine with aura or those aged 35 and older who smoke ≥ 15 cigarettes daily [26]. Hypertension history and current blood pressure should be documented before starting COC and during follow-up visits, though this is not required for progestin-only pill contraceptives [26]. Clinicians should establish with reasonable certainty that a patient is not pregnant before starting oral contraceptives [26]. Pregnancy tests are not required but may be considered based on clinical judgment [26]. COCs can be started at any point during the menstrual cycle [26]. Clinicians should document potential drug interactions before prescribing COC (Table 1). While rifampin and griseofulvin reduce COC effectiveness, they are not absolute contraindications [28, 29]. We recommend dermatologists download and use the “Contraception” smartphone app, developed by the Centers for Disease Control and Prevention, which provides the latest US Medical Eligibility Criteria and US Selected Practice Recommendations for contraceptive use. The smartphone app can help guide COC and other contraceptive discussions for patients with medical comorbidities [30].

Table 1.

Relevant examination and medical history to assess comorbidity profile for combined oral contraceptives (COC) based on US guidelines^a

Documentation	Contraindications: category IVb
Examination
Blood pressure reading	≥ 160/100 mmHg
Body mass index: weight, height	Not applicable (NA)
Medical history
Are you currently pregnant?	Current pregnancy
Have you had a baby in the last 3 weeks?	Postpartum < 3 weeks
Are you breastfeeding?	Breastfeeding and postpartum < 3 weeks
Meets Centers for Disease Control and Prevention criteria for reasonable certainty that a patient is not pregnant	NAd
1. No signs and symptoms of pregnancy AND
2. Have you had sexual intercourse since the start of your last normal menstrual period?: NO
3. Are you currently using a reliable method of contraception?c: YES
4. Are you within 4 weeks postpartum?: YES
5. Are you within the first 7 days after an abortion or miscarriage?: YES
6. Did your last menstrual period start within the past 7 days?: YES
7. Are you breastfeeding exclusively or almost exclusively (> 85% of feeds) and < 6 months postpartum? Have you not had your period return since childbirth? Are you within 6 months of postpartum?: YES
Risk factors for atherosclerotic cardiovascular disease	Has > 1 risk factor for atherosclerotic cardiovascular diseasee
Do you have high blood pressure?
Do you take medicine for high cholesterol?
How old are you? Do you smoke? How many cigarettes do you smoke a day?	Age ≥ 35 and currently smokes ≥ 15 cigarettes per day
Have you ever had a blood clot in your lung or leg, not including varicose veins? Do you have a history of recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE)? Do you have active cancer or a history of cancer treatment within the past 6 months?	Current or history of DVT/PE with a higher risk of recurrencef
Do you have a history of thrombophilia?	Thrombophiliag
Do you have systemic lupus erythematosus? Have you ever had your antiphospholipid antibodies checked?	Systemic lupus erythematous with positive or unknown antiphospholipid antibodies
Do you have sickle cell disease?	Sickle cell disease
Have you had major surgery with prolonged immobilization?	Major surgery with prolonged immobilization
Do you have heart disease? Have you had a heart attack or stroke?	Current or history of ischemic heart disease Stroke Peripartum cardiomyopathy with moderate or severely impaired cardiac functionh
Have you been diagnosed with valvular heart disease? Do you have pulmonary hypertension or a history of atrial fibrillation?	Complicated valvular heart diseasei
Do you have diabetes? If yes, do you have any diagnosed issues with your kidneys, eyes, or nerves?	Diabetes with nephropathy, retinopathy, or neuropathy Diabetes for > 20 years Diabetes with vascular disease
Do you have chronic kidney disease or require dialysis?	Chronic kidney disease with nephrotic syndrome Chronic kidney disease on hemodialysis or peritoneal dialysis
Do you have or have you had breast cancer?	Current breast cancer
Do you have liver disease, such as hepatitis or cirrhosis, or have you had liver cancer?	Viral hepatitis Severe cirrhosis Hepatocellular adenoma or carcinoma COC-related cholestasis
Have you had a solid organ transplant? If so, was there graft failure?	Solid organ transplantation with graft failure
Do you have migraine headaches with aura?	Migraines with aura
Do you have gallbladder disease?	NA
Do you take medicine for seizures or tuberculosis like carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, lamotrigine, rifampin, or rifabutin?	NA
Do you take any antibiotics?	NA
Do you take any medications for human immunodeficiency virus prevention or treatment like fosamprenavir?	NA

^aTable developed with reference to the Centers for Disease Control and Prevention United States Medical Eligibility Criteria for Contraceptive Use, 2024 [26]

^bCategory IV contraindications are those deemed an unacceptable health risk if the contraceptive method is used [26]

^cReliable contraception methods include long-acting reversible contraceptives, combined oral contraceptives, progestin-only pills, patches, vaginal rings, injectables, consistent use of condoms, and permanent methods (vasectomy or tubal ligation) [26]

^dIf pregnancy status is uncertain, starting the implant, depot medroxyprogesterone acetate, combined hormonal contraceptives, or progestin-only pills will likely outweigh potential risks. Follow-up with a pregnancy test in 2–4 weeks [26]

^eRisk factors for atherosclerotic cardiovascular disease include age ≥ 35 years, smoking, diabetes, hypertension, low-high density lipoprotein, high–low-density lipoprotein, and high triglycerides [26]

^fPatients with a higher risk of recurrent DVT/PE have thrombophilia, active cancer (except non-melanoma skin cancers), history of recurrent DVT/PE, or are within 6 months of cancer remission

^gThrombophilia diagnoses include factor V Leiden mutation, prothrombin gene mutation, protein S, protein C, antithrombin deficiencies, or antiphospholipid syndrome

^hNew York Heart Association Functional Class III or IV

ⁱComplicated valvular disease includes pulmonary hypertension, atrial fibrillation risk factors, or history of bacterial endocarditis

Potential risk of venous thromboembolism (VTE) increases with COC use [31]. Baseline VTE incidence is low among non-pregnant women of reproductive age not taking COC, with an estimated 5–10 events per 10,000 person-years [32]. VTE incidence among COC users is higher and ranges from 8–10 events per 10,000 person-years [33]. Certain COCs are associated with increased risk of VTE [33, 34]. Drospirenone-containing COCs have a 1.5–2.0-times higher VTE risk than levonorgestrel-containing COC, based on a meta-analysis of 22 studies with 15,918 non-pregnant female participants [33]. COCs containing natural estrogens (e.g., E2, estetrol) are associated with a 33% lower VTE risk than COCs containing EE based on a meta-analysis of five studies with 560,152 women [34]. Dermatologists may recommend primary care follow-up for VTE risk assessment and management, including counseling or treatment for weight loss or smoking cessation (Table 1) [26].

Potential side effects influence patient decisions about COC use. Common side effects include intermenstrual bleeding (10.5%), headache (8.6%), and nausea (6.4%) based on a clinical trial of drospirenone/EE for moderate acne [9]. COC benefits include the reduction of menstruation-related migraines, endometriosis pelvic pain, and premenstrual dysphoria [35]. American College of Obstetricians and Gynecology guidelines on the non-contraceptive use of COC may assist in clinical decision-making [36].

COC use is common among US adolescents aged 15–19, with 54% reporting a history of COC use [37]. Low-dose COC formulations containing EE and levonorgestrel or drospirenone are effective for moderate acne treatment in adolescents aged ≥ 14 years old [10, 12]. However, COC use during adolescence may affect peak bone mineral density gain, which typically occurs between ages 16 and 19 [38]. First-time adolescent COC users had lower mean bone mineral density at the lumbar spine after 12 months (− 0.33) and 24 months (− 0.83) of use compared to non-users, according to a meta-analysis of 2420 adolescents aged 12–19 [38]. Although data on COC safety in patients under 14 are limited, current evidence supports their use in the treatment of moderate acne in adolescents. Further research will aid in expanding COC use among younger populations. Dermatologists should follow the American Academy of Pediatrics guidelines when prescribing COC to adolescents. The guidelines recommend that clinicians treating adolescents provide accurate information on COC risks and benefits, ensure patient confidentiality, and follow state-specific minor consent laws for contraceptive use.

Differences in efficacy and time to visible acne improvement can guide treatment selection and counseling. Topical and oral antibiotics achieved a greater reduction in total acne lesions compared to oral contraceptives at 3 months (mean difference: 48.0% vs 37.3%) but had similar outcomes at 6 months (52.8% vs 55.0%) in a meta-analysis of 32 clinical trials with 3217 female participants [39]. Oral isotretinoin may be more effective at treating acne, as it achieved a greater reduction in total acne lesions than four COCs (48.4% vs 8.0–20.8%) in a network meta-analysis of 221 clinical trials with 65,601 participants [40].

Combination therapy with COC and other acne treatments is an emerging approach with gaps in current evidence. COC combined with daily topical 20% micronized azelaic acid cream reduced mean scar severity (48.0% vs 42.0%), pigmentation index (34.0% vs 9.0%), and erythema index (31.0% vs 12.0%) more than COC alone in a 6-month clinical trial of 23 female participants with moderate-to-severe acne [41]. More patients achieved 95–100% reduction in Investigator’s Global Assessment (IGA) severity scores with the combination therapy (58.0% vs 45.0%) [41]. Spironolactone 100 mg/day combined with drospirenone/EE achieved ≥ 75% reduction in acne lesions in 74% of women with severe acne, with no cases of hyperkalemia among a prospective cohort of 27 participants [42]. Drospirenone 3 mg has anti-mineralocorticoid potency comparable to spironolactone 20–25 mg, though the clinical relevance of this equivalency in acne treatment remains unclear [43].

Shared decision-making is a collaborative process in which patients and physicians work together to make informed choices about medical care [44]. In contraceptive counseling, this approach improves patient satisfaction and treatment adherence [44]. Patients are involved in the decision-making process without feeling pressured into contraceptive treatment and have full awareness of alternative options. Dermatologists should explain the risks and benefits of COC and clarify common misconceptions such as fears about permanent fertility loss or birth defects [45]. The Bedsider website can be used by patients to learn more about contraceptive options and promote informed decision-making [46]. Gynecologist referrals may be necessary for further evaluation.

Other Hormonal Contraceptives

Dermatologists play a key role in educating patients and reproductive health clinicians on the effects of contraceptives on the skin. Patients may be prescribed non-oral contraceptives by reproductive health clinicians [47–49]. Data on acne outcomes for these methods are limited to contraceptive efficacy trials, and no existing evidence exists to support their use for acne treatment [47]. Acne rates were similar between oral and patch levonorgestrel/EE formulations (1.4% vs 1.1%) after six cycles in a clinical trial of 1504 female participants [50]. Vaginal ring users were less likely to report acne than COC users taking levonorgestrel/EE (odds ratio [OR] 0.23), drospirenone/EE (OR 0.18), or norgestimate/EE (OR 0.19) in a systematic analysis of three clinical trials with 1644 female participants [47].

Long-acting reversible contraceptives (LARC) include progestin-only levonorgestrel intrauterine devices (IUD) and etonogestrel implants. While LARCs are effective contraceptives, they are associated with a higher acne risk than COCs [51–53]. New levonorgestrel IUD users had an increased risk of clinical encounters for acne (hazard ratio [HR] 1.14 and 1.09) compared with new COC users in a retrospective cohort of 336,738 female patients [52]. New levonorgestrel IUD users had a higher risk of escalating treatment from topical medications to oral tetracycline-class antibiotics (HR 1.44 and 1.34, respectively), while etonogestrel implant users had a lower risk (HR 0.70) than COC users based on a retrospective cohort study of 21,178 women with a history of acne [52]. Progestin-only IUDs or implants were associated with new or worsening acne in 28.5% of users after 8 weeks, though discontinuation due to acne was rare (3%) in a prospective cohort of 1319 female participants [53]. Progestin-only IUD users had higher odds of new-onset acne (OR 2.51) within 1 year of implantation than users of the copper IUD in a retrospective cohort of 1224 women without history of skin conditions [51].

Clascoterone

Clascoterone (also known as cortexolone 17α‐propionate) is a topical androgen receptor inhibitor that blocks dihydrotesterone’s effects on the skin, reducing sebum production and inflammation [54]. Topical clascoterone 1% cream (Winlevi®; Sun Pharmaceutical Industries, Inc.) is FDA approved for acne treatment in male and female patients aged ≥ 12 years [54]. The AAD conditionally recommends topical clascoterone for acne management based on high-certainty evidence [55–57].

Twice daily clascoterone 1% cream showed superior treatment success (19.9% vs 7.7%) over vehicle, as measured by an IGA score of “clear” or “almost clear” with a ≥ 2-point reduction from baseline in two clinical trials of 1421 male and female participants with moderate-to-severe facial acne [58]. Adverse local skin reactions were similar to the vehicle and included skin scaling/dryness (10.5% vs 6.5%), stinging/burning (4.2% vs 1.3%), and striae rubrae (2.5% vs 0.3%) [54]. Topical clascoterone is minimally absorbed into the bloodstream and is unable to affect the hypothalamic-pituitary-gonadal axis or reproductive functions [54]. However, mild hypothalamic-pituitary-adrenal axis suppression was observed in five pediatric patients with decreased cosyntropin levels after 2 weeks of use, though vital signs and electrocardiograms remained stable [59].

Twice-daily clascoterone 1% cream was more effective in reducing non-inflammatory (− 0.28) and inflammatory (− 0.25) lesion counts than once-daily application, based on a meta-analysis of seven clinical trials involving 2006 male and female participants with moderate-to-severe facial acne [60]. Despite its effectiveness, a 1-month supply of topical clascoterone costs between US$300 to US$600, which may limit financial accessibility, particularly for uninsured patients [61].

The efficacy of topical clascoterone has been compared to other acne treatments. Once-daily clascoterone 1% cream achieved a 50% improvement in total lesion count faster than once-daily tretinoin 0.05% cream (median: 43.5 vs 57.0 days) in a clinical trial of 77 men with mild-to-moderate facial acne [62]. Topical clascoterone achieved higher IGA-defined treatment success rates than placebo than topical adapalene (OR 3.40 vs 1.70) in a network meta-analysis of 221 clinical trials with 65,601 men and women [40]. Topical clascoterone had lower odds of discontinuation because of adverse events (OR 0.36) compared to placebo than topical trifarotene (OR 11.36; 2% discontinuation rate), tazarotene (OR 6.08), and tretinoin (OR 3.17) [40]. Daily spironolactone 200 mg achieved a greater reduction in total lesion count compared to placebo than twice-daily clascoterone 1% cream (4.46 vs 0.27) based on network meta-analysis of 7 clinical trials across 2006 female and male participants with moderate-to-severe acne [60]. Oral isotretinoin achieved a greater reduction in total (48.4% vs 16.3%), inflammatory (54.2% vs 16.4%), and non-inflammatory lesion counts (12.1% vs 48.5%) compared to placebo than clascoterone 1% cream [40].

Spironolactone

Spironolactone is a potassium-sparing diuretic with anti-androgenic properties and is used off-label for acne treatment [63]. Spironolactone blocks 5α-reductase receptors in sebaceous glands and reduces testosterone production, which decreases sebum levels [64]. The AAD conditionally recommends oral spironolactone for acne treatment based on moderate-certainty evidence [55, 65–72]. Spironolactone 50–100 mg/day significantly improved acne-related quality of life scores (mean difference 1.27) in a 12-week clinical trial of 410 women with facial acne [73]. Common side effects include polyuria (31%), irregular menstrual bleeding (28%), breast tenderness (20%), headaches (20%), and dizziness (19%) [73].

Spironolactone is an emerging treatment for adolescent acne, with a two-to-three-fold increase in prescriptions among adolescents aged 13 to 19 from 2014 to 2018 [74]. Spironolactone (median dose 100 mg/day) was associated with a complete acne treatment response in 22.5% of a retrospective cohort of 80 female adolescents with a median time of 3 months to initial response and low hyperkalemia incidence (0.2%) [75]. Side effects in adolescents included headache (1.3%), rash (1.3%), breast tenderness (1.3%), and diarrhea (1.3%) [75].

Spironolactone may be suitable for long-term acne management in female patients. Spironolactone 50–200 mg/day was well tolerated during acne treatment despite side effects, which included polyuria (29%) and menstrual irregularities (22%), during an 8-year observational study of 210 women [76]. Few patients discontinued treatment because of side effects (15%), though others discontinued because of treatment failure (29%) [76]. Spironolactone 150 mg/day reduced global acne scores more than doxycycline 100 mg/day (62% vs 32%) in a 6-month clinical trial of 133 women with moderate acne [77]. Combining drospirenone/EE with spironolactone 100 mg/day for 6 months resulted in fewer menstrual irregularities compared to spironolactone 100 mg/day alone for 3 months (15% vs 50%) in prospective cohorts of 27 and 35 women with facial acne [42, 78].

The FDA prescribing label lists theoretical risks of feminization of male fetuses and cancer from spironolactone based on animal studies with limited human evidence [63, 79]. Male fetus feminization has been linked to high-dose maternal spironolactone use (> 200 mg/day) in five animal studies [79]. Spironolactone is FDA approved to treat edema in pregnant women at doses of 25–200 mg/day [63]. No human studies have shown male feminization at birth with spironolactone doses of 25–400 mg/day during pregnancy, though human data remain limited [79]. Gynecomastia was observed in a dose-dependent manner among 32 men treated with twice-daily spironolactone, starting at 50 mg (30%) or 100 mg (62%) and titrated up to double the initial dose over an 8-month clinical trial [80]. Gynecomastia occurred in 13% of 23 men treated with spironolactone, starting at 200 mg/day and gradually titrated down to 50 mg/day over a 20-week prospective cohort study [67].

In animal studies, spironolactone at doses greater than the human equivalent of 200 mg/day showed no evidence of increased cancer risk. In human studies, spironolactone 100–400 mg/day was not associated with an increased risk of breast, prostate, ovarian, esophageal, kidney, gastric, or bladder cancers in a meta-analysis of a pooled retrospective cohort of 4,528,332 adults [81]. Spironolactone treatment was not associated with increased breast cancer risk compared with non-systemic acne treatments in a retrospective matched cohort of 101,502 women with acne [82]. Spironolactone combined with oral tetracycline-class antibiotics was associated with lower risks of breast cancer than spironolactone alone in a retrospective cohort of 196,495 female patients treated for acne [82].

The risk of hyperkalemia with oral spironolactone varies depending on age, cardiac, and renal function [63]. Oral spironolactone is contraindicated in patients with acute renal insufficiency, significantly impaired renal function, hyperkalemia, anuria, Addison’s disease, and patients taking eplerenone [63]. The FDA mandates serum potassium monitoring for patients with severe heart failure (New York Heart Association class III–IV) and recommends beginning to monitor 1 week after starting or increasing the spironolactone dose [63]. Hyperkalemia incidence was higher in women aged 46–65 than in younger women (16.7% vs 0.9%) within 1 year of starting spironolactone for acne, based on a retrospective cohort of 618 women [71]. Hyperkalemia risk related to spironolactone treatment for acne was 0.7% in a retrospective cohort of 974 women, similar to the population’s baseline rate (0.8%) with or without spironolactone use [68].

Topical spironolactone may be an effective acne treatment with fewer systemic side effects than the oral formulation [83, 84]. Topical spironolactone is only available as a compounded cream, gel, or solution, and compounded medications are not FDA-approved [61]. Dermatologists should inform patients about the potential risks of unpredictable side effects and lack of standardized efficacy testing with compounded treatments [61]. Compounding pharmacies should be selected that meet national standards and comply with state and federal regulations [61]. Topical spironolactone 2% solution applied twice daily achieved a greater mean reduction in comedone (by 4.6), papule (by 3.8), and pustule (by 1.9) counts compared to once-daily topical clindamycin 1.5% solution in a 12-week clinical trial of 35 men and women with mild-to-moderate acne [85]. Topical spironolactone 5% gel applied twice daily reduced total lesion count by 71% compared to 36% with the inactive gel base (vehicle) in a clinical trial of 38 participants [86]. Common side effects compared to the vehicle include burning (21.7% vs 10.5%), erythema (8.3% vs 5.2%), dryness (15% vs 2.7%), and itching (15% vs 2.7%) [87]. Side effects were less frequent with topical spironolactone 1% in a lipid carrier gel compared to spironolactone 5% alcoholic gel when applied twice daily for 8 weeks in a clinical trial of 76 participants with mild-to-moderate acne [87].

Future Research

Further research on hormonal therapies is essential to develop more inclusive acne management strategies, particularly for men and pediatric patients. Expanding evidence-based approaches for these populations will address gaps in hormonal acne treatments. Emerging strategies include 5α-reductase inhibitors, drospirenone, and COC.

5α-reductase inhibitors lower serum dihydrotestosterone levels, which is associated with reduced sebum production in the scalp and skin [88]. Oral dutasteride is FDA approved for androgenetic alopecia in men and women and is more effective than finasteride at reducing dihydrotestosterone levels [88]. Dutasteride 0.500 mg/day was shown to reduce acne severity from moderate to mild after 3 months in a case study of androgenic alopecia and acne in two men [89]. Common side effects in men include decreased libido (2.4–10.0%) and erectile dysfunction (3.4–15.8%), though side effects are mild and may resolve over time during treatment [90]. Dutasteride is contraindicated in persons of childbearing potential because of concerns of potential teratogenicity, though these data are based on limited evidence from non-human animal studies [90].

Drospirenone is a spironolactone derivative available as a progestin-only pill (Slynd^®; Exeltis USA, Inc.). VTE risk is lower for drospirenone-only pills compared to COC formulations with drospirenone [91]. Drospirenone 4 mg/day was associated with less incident acne than desogestrel 0.075 mg (5.1% vs 3.0%) in an 18-month clinical trial of 1213 women [92]. Drospirenone demonstrates a favorable safety profile for continuous menstrual suppression in adolescents, with low acne incidence (2.9%) [93]. However, acne outcome data for drospirenone are from contraceptive efficacy trials rather than dedicated acne studies, indicating the need for more focused research in this area.

Increasing access to hormone therapy for acne treatment can reduce dermatologists’ reliance on antibiotics for acne, which aligns with CDC goals for antibiotic stewardship [94]. Dermatologists should limit oral antibiotic duration for acne to 3–4 months, as extended use increases the risk of antibiotic resistance and infections, which include Clostridium difficile, Candida vulvovaginitis, and Malassezia folliculitis [55, 94]. Oral spironolactone and COCs are safe, effective treatments for long-term acne management in women, with similar or better efficacy at 6 months than oral antibiotics [26, 76]. However, more data are needed to compare the efficacy of spironolactone and oral antibiotics, as clinical trial data lack generalizability to women of color, patients < 20 years of age, and non-tetracycline-class antibiotics [73, 77]. Discomfort with contraceptive counseling in dermatology is a potential barrier to the prescription of hormonal therapies for acne [95].

Conclusion

Hormonal therapies are effective acne treatments and include combined oral contraceptives, spironolactone, and clascoterone. Different COC formulations show comparable efficacy in acne management. Spironolactone is a first-line treatment for women with acne, with minimal need for routine potassium monitoring. Clascoterone is a topical treatment for men and women, with limited systemic absorption and a reduced risk of reproductive hormone side effects than systemic hormonal therapies. Dermatologists should engage in shared decision-making during contraceptive counseling. Acne treatment tailored to patient preferences and comorbidity profiles will promote treatment adherence and the safe use of hormonal therapies. Expanding the use of hormonal therapies to men and pediatric patients will increase access to effective acne treatments while reducing reliance on oral antibiotics.

Declarations

Conflict of Interest

Dr. Howa Yeung reports receiving grant funding from the American Acne and Rosacea Society, Dermatology Foundation, and the Department of Veterans Affairs unrelated to the submitted work, honorarium from the American Academy of Dermatology, and has served on the advisory boards of Sanofi-Genzyme, and L'Oréal Dermatological Beauty. Courtney A. Smith, Emily Gosnell, Turkan Banu Karatas, Chelsea Deitelzweig, and Dr. Elizabeth Collins have no conflicts to declare.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.