Hormonal Treatment for Acne
It Can Help Females, but There Are Limitations Regarding Women Who Are Pregnant or Breastfeeding
The Essential Information
In both males and females, hormones play a significant role in acne, specifically hormones called androgens, which are male hormones found in both males and females.
There's not much that boys and men can do about these hormones, because hormonal treatments can cause feminization of the male body, including breast growth, as well as other undesirable side effects.
However, doctors sometimes prescribe hormonal treatment to girls and women who are not pregnant or breastfeeding.
Hormonal treatments reduce the amount of androgens, which in turn decreases skin oil production, and ultimately reduces acne symptoms.
- Combined oral contraceptives (COCs), otherwise known as birth control pills (most common - reliably reduces acne by about 60%)
- Cyproterone acetate (CPA)
- GnRH agonists
Because hormonal treatments are oral treatments, they affect the entire body and can come with a large array of side effects. This is why it is important to consult your physician about hormonal treatments and educate yourself as much as possible on the risks.
Many females experience acne flares approximately 7 - 10 days before menstruation and then improvement in their acne once menstruation starts. These cyclical acne symptoms are a result of the fluctuation of several different hormones during the menstrual cycle. Each of these hormones plays a different role in acne:
- Androgens (male hormones present in both males and females): More androgens normally means more skin oil (sebum) production, and in turn, more acne. High levels of androgens are associated with acne in both males and females.
- Estrogens (female hormones present in both males and females): More estrogens normally means less sebum production, and in turn, less acne. Estrogens also may reduce inflammation.
- Progesterone (hormone present in both males and females): May play a role in fluctuating levels of sebum during the menstrual cycle. This is a matter of debate among researchers.1-4
Hormonal Treatments for Acne
Because acne is a hormonal disease, hormonal treatments are sometimes used to acne. Available hormonal treatments include:
- Combined oral contraceptives (COCs), otherwise known as birth control pills
- Cyproterone acetate (CPA)
- GnRH agonists
Let's have a look at the effectiveness and side effects of each, starting with by far the most commonly prescribed hormonal treatment for acne, combined oral contraceptives (COCs).
Combined Oral Contraceptives (COCs)
Combined oral contraceptives (COCs) are birth control pills that contain both ethinyl estradiol (synthetic estrogen) and progestin (synthetic progesterone). In addition to preventing pregnancy, the estrogen in COCs reduces sebum and may reduce the level of androgens, both of which reduce acne symptoms. The role of progestin in COCs is not understood as is that of estrogen and appears to vary somewhat according to the type of progestin.5
There are several types of progestin that can be present in COCs, including cyproterone acetate (CPA), chlormadinone, drospirenone, and derivatives of 19-nortestosterone, such as norethindrone, levonorgestrel, norgestrel, desogestrel, norgestimate, and gestodene.5
There are many COCs on the market. In the United States, the FDA (Food and Drug Administration) approved three COCs containing the progestins, norgestimate (Ortho Tri-Cyclen ®), norethindrone (Estrostep®), and drospirenone (YAZ®) for acne treatment. However, many other COCs also are effective in treating acne. Other countries approved other COCs for acne, including those that contain CPA.5
Effectiveness: Regardless of which ones are approved in any particular country, all COCs show evidence of effectively treating acne in women. Combined oral contraceptives cannot be used in men.
A 2012 systematic review (a rigorous literature review that pools the results of many studies) concluded that all COCs resulted in a significant reduction of acne lesions and acne severity. The review concluded also that COCs containing CPA appeared to be more effective than the other progestins studied, but the evidence for this was limited.5
A 2014 meta-analysis (another rigorous literature review that pools the results of many studies and combines them into a single analysis) compared the effectiveness of COCs with a placebo. This meta-analysis found that after three months of COC treatment, there was a 35% reduction in acne lesions, and after six months of treatment, there was a 55% - 60% reduction.6
Side effects: The most serious side effects of COCs are thromboembolisms, which is a type of blood clot that can cause severe problems and even death. Therefore, COC-use is not advised in women with predisposing factors that raise their risk of a thromboembolism, such as genetic clotting disorders, previous thromboembolisms, heart disease, high blood pressure, obesity, smoking in women older than 35 years of age, diabetes, liver disease, migraine and headache, prolonged immobilization, such as long-term bed rest, history of breast, endometrial, or liver cancer, pregnancy and breast feeding, or hypersensitivity to any ingredient in a COC.5
Other safety concerns are related to the estrogen in COCs and include breast tenderness, heart disease, headache, nausea, blood clotting problems, and risk of uterus and breast cancers. Newer COCs that contain a lower dose of estrogen carry a lower risk of these side effects.5
Finally, combining a COC with an antibiotic may reduce the effectiveness of the COC if it is used for birth control. There is some evidence that doxycycline and tetracycline, which commonly are used for acne, do not affect the effectiveness of COCs. However, if you are trying to prevent pregnancy, it is wise to employ a second method of birth control when taking any antibiotic with a COC.5
Cyproterone acetate (CPA) is a progestin that often is present in a COC, but it can be used alone. Cyproterone acetate works as an anti-androgen: it blocks androgen receptors and decreases the production of androgens. Because of these effects, cyproterone acetate would cause feminization in men who took it. It also cannot be used in pregnant women.5,7
Effectiveness: Based on two 1990s studies, CPA used alone in the recommended dose of 50 - 100mg per day can result in 75% - 90% improvement in acne within three months.5
Side effects: The most common side effects of CPA are irregularity in the menstrual cycle, breakthrough bleeding (bleeding between periods), breast tenderness, headache, and nausea. However, these side effects typically are temporary or go away with time. Using CPA in a COC rather than alone significantly reduces the menstrual side effects.5
A less common but more concerning side effect of CPA is liver damage. This is dose dependent, meaning that higher doses carry more risk.5
Spironolactone is a derivative of a natural hormone called aldosterone. Spironolactone is an anti-androgen, so it cannot be used in men or in pregnant women since it can cause feminization of a male fetus.5,7
Effectiveness: A 2009 systematic review concluded that because of the limited number of studies and the inadequate number of patients in each study, the effectiveness of spironolactone remains unproven. A more recent 2017 review came to the same conclusion.8 However, the review authors also noted that until more rigorous evidence becomes available, we must rely on doctors' experience, which suggests that spironolactone does work to improve acne.
Expand to read details of 2017 systematic review
This systematic review was published in the American Journal of Clinical Dermatology. The authors looked at 10 clinical trials and 21 case studies on spironolactone. They concluded there is not enough rigorous evidence to show that spironolactone is effective against acne at the doses doctors typically prescribe. They noted that higher doses, such as 200 mg per day, seem to be effective against acne, but doctors are hesitant to prescribe such high amounts due to the increased risk of side effects. In conclusion, the authors wrote, "Prescribing recommendations must continue to rely on consensus and expert opinion until high-quality evidence becomes available."8 In other words, if doctors' experience suggests that spironolactone works, that's the best information we have to go on for now.
In fact, doctors have been using spironolactone for more than 30 years to treat hormone-related skin diseases, such as acne. Some studies show spironolactone to be effective in treating acne on the face, chest, and back in both adolescent and adult females. Some of these studies indicate that at standard doses of 50 - 100mg once or twice per day, improvement can be seen within three months.5,9 For example, three studies published in 2017 found that 71%-86% of female patients improve on spironolactone.10-12
Expand for details of three studies from 2017
The first 2017 study was published in the journal Dermatology. The researchers looked through the medical records of 400 female acne patients who had been treated with spironolactone during the preceding four years. Of these, 253 patients started taking spironolactone after trying other acne treatments, and 147 patients took spironolactone as their first and only acne treatment.
The researchers found that 86% of the patients experienced an improvement in acne after taking spironolactone. The study authors wrote, "The vast majority of our patients improved on spironolactone, despite many previously failing other acne treatments."10
The second 2017 study was published in the European Journal of Dermatology. As in the previous study, the researchers went through past medical records of women with acne. They came up with 70 women who took 150 mg or less of spironolactone per day for an average of 6 months. The researchers found that for 71% of the women, spironolactone was effective at reducing acne.11
The third 2017 study was published in the International Journal of Women's Dermatology. Like the previous two studies, this study relied on past medical records of female patients. Out of 110 female patients, 85% experienced an improvement in acne after taking spironolactone. On average, the women's acne improved by 73% on the face, 76% on the chest, and 78% on the back after taking spironolactone.
However, the researchers noted that some of the women took other acne medications at the same time as spironolactone, making it difficult to be sure that spironolactone alone was responsible for the improvement. The scientists highlighted the need for studies testing spironolactone on new patients in a controlled manner instead of using past medical records.12
Side effects: Spironolactone can cause menstrual irregularities and tenderness or enlargement of the breasts. However, these side effects typically are mild and more common at higher doses. In addition, spironolactone can cause a high potassium level in the bloodstream, though this is not much of a concern in young, healthy acne patients. Nevertheless, people taking spironolactone should avoid taking ACE-inhibitors (a type of high blood pressure medication) or potassium supplements.5,7
Flutamide is an anti-androgen that is used to treat prostate cancer. It works as an anti-androgen by blocking androgen receptors.5,7
Effectiveness: A 2011 clinical trial indicated that flutamide was as effective as, or maybe even more effective than COCs with CPA in treating acne lesions.9 However, the authors suggested that their results should be confirmed in further future studies with larger numbers of patients.13 Other studies indicate that at the standard dose of 62.5 - 500mg per day, it can result in an 80% improvement in acne.5
Side effects: The most concerning side effect of flutamide is liver toxicity, which appears to be related to dose and older age. Because of this, researchers advise starting with a low dose and increasing the dose only if necessary.
According to a 2015 article in the British Journal of Dermatology, "Monitoring of liver function is mandatory [when taking flutamide] as cases of fatal [liver toxicity] have been reported."5
Other side effects include diarrhea, hematological disorders (disorders of the blood), muscle cramps, and breast enlargement.9 Finally, because flutamide can transfer between a pregnant woman and her fetus, it cannot be taken during pregnancy.5
Gonadotropin-releasing hormone agonists (GnRH agonists), such as buserelin, nafarelin, and leuprolide, suppress hormones that stimulate androgen production. These medicines are reserved for women who do not respond to or who cannot tolerate COCs.5
Effectiveness: There is some evidence that GnRH agonists may help treat acne, but their use is limited because of high costs. In addition, there are no controlled trials of GnRH agonists - partly because of the high cost and partly because they can cause menopausal symptoms.5,7
Side effects: While GnRH agonists suppress androgens, they also suppress the production of estrogens. The lack of estrogen may lead to menopausal symptoms, such as bleeding, osteoporosis, and flushing. GnRH agonists cannot be used during pregnancy, breastfeeding, or if there is vaginal bleeding unrelated to periods.7,14
Oral corticosteroids, such as prednisone, reduce the production of androgens. These medications are the only hormonal treatments that can be given also to men. In addition, they are advised only for acne that is caused by a condition called congenital adrenal hyperplasia (overgrowth of the adrenal gland that is present at birth). Congenital adrenal hyperplasia causes excessive production of androgens because of a lack of natural hormones: low doses of corticosteroids correct this issue.5
Effectiveness: Studies show that low doses of prednisone (2.5 - 15mg per day) alone or in combination with a COC can be effective in treating acne.5,15,16
A 1983 study in the British Journal of Dermatology gave 14 acne patients a low dose of prednisone. The authors reported that after four months of treatment, patients' acne improved. The authors stated, "Three patients felt their acne was better, seven patients were much better and four patients reported no change."16
Several case studies have also demonstrated the effectiveness of prednisone in the treatment of a rare, severe form of acne called acne fulminans.17,18
Side effects: Corticosteroid treatment should not exceed six months because corticosteroids are associated with the risk of osteoporosis (thinning of the bones, which can result in fractures), even at low doses.7 Most doctors leave corticosteroids as a last resort because they can cause serious side effects, especially when taken long term or at high doses.
- Raghunath, R. S., Venables, Z. C. & Millington, G.W. The menstrual cycle and the skin. Clin Exp Dermatol 40, 111 - 115 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25683236
- Farage, M. A., Neill, S. & MacLean, A. B. Physiological changes associated with the menstrual cycle: a review. Obstet Gynecol Surv 64, 58 - 72 (2009). https://www.ncbi.nlm.nih.gov/pubmed/19099613
- Arora, M. K., Yadav, A. & Saini, V. Role of hormones in acne vulgaris. Clin Biochem 44, 1035 - 1040 (2011). https://www.ncbi.nlm.nih.gov/pubmed/21763298
- Lam, C. L. & Zaenglein, A. L. Contraceptive use in acne. Clin Dermatol 32, 502 - 515 (2014). https://www.ncbi.nlm.nih.gov/pubmed/25017461
- Bettoli, V., Zauli, S. & Virgili, A. Is hormonal treatment still an option in acne today? Br J Dermatol 172 suppl 1, 7 - 46 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25627824
- Koo, E. B., Petersen, T. D. & Kimball, A. B. Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris. J Am Acad Dermatol 71, 450 - 459 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24880665
- Katsambas, A. D. & Dessinioti, C. Hormonal therapy for acne: why not as first line therapy? Facts and controversies. Clin Dermatol 28, 17 - 23 (2010). https://www.ncbi.nlm.nih.gov/pubmed/20082945
- Layton, A. M., Eady, E. A., Whitehouse, H., Del Rosso, J. Q., Fedorowicz, Z. & van Zuuren, E. J. Oral spironolactone for acne vulgaris in adult females: A hybrid systematic review. Am J Clin Dermatol 18, 169-191 (2017). https://pubmed.ncbi.nlm.nih.gov/28155090/
- Husein-Elahmed, H. Management of acne vulgaris with hormonal therapies in adult females. Dermatol Ther 28, 166 - 172 (2015). https://www.ncbi.nlm.nih.gov/pubmed/25845307
- Grandhi, R,. & Alikhan, A. Spironolactone for the treatment of acne: A 4-year retrospective study. Dermatology 233, 141-144 (2017). https://pubmed.ncbi.nlm.nih.gov/28472793/
- Isvy-Joubert, A., Nguyen, J. M., Gaultier, A. et al. Adult female acne treated with spironolactone: a retrospective data review of 70 cases. Eur. J. Dermatol. 27, 393 - 398 (2017). https://www.ncbi.nlm.nih.gov/pubmed/28862134
- Charny, J. W., Choi, J. K. & James, W. D. Spironolactone for the treatment of acne in women, a retrospective study of 110 patients. Int. J. Womens Dermatol. 3, 111 - 115 (2017). https://www.ncbi.nlm.nih.gov/pubmed/28560306
- Adalatkhah, H., Pourfarzi, F. & Sadeghi-Bazargani, H. Flutamide versus a cyproterone acetate-ethinyl estradiol combination in moderate acne: a pilot randomized clinical trial. Clin Cosmet Investig Dermatol 4, 117-121 (2011). https://pubmed.ncbi.nlm.nih.gov/21833162/
- Elsaie, M. L. Hormonal treatment of acne vulgaris: un update. Clin Cosmet Investig Dermatol 9, 241 - 248 (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015761/
- Zaenglein, A. L. et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 74, 945 - 973 (2016). https://www.ncbi.nlm.nih.gov/pubmed/26897386
- Darley, C. R., Moore, J. W., Besser, G. M., Munro, D. D. & Kirby, J. D. Low dose prednisolone or oestrogen in the treatment of women with late onset or persistent acne vulgaris. Br J Dermatol 108, 345 - 353 (1983). https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2133.1983.tb03974.x
- Lages, R. B., Bona, S. H., Silva, F. V., Gomes, A. K. & Campelo, V. Acne fulminans successfully treated with prednisone and dapsone. An Bras Dermatol 87, 612-614 (2012). https://pubmed.ncbi.nlm.nih.gov/22892777/
- Proença, N. G. Acne fulminans. An Bras Dermatol 92 (5 Suppl 1), 8-10 (2017). https://pubmed.ncbi.nlm.nih.gov/29267432/