Editing Acne (section)

===Medications===

====Benzoyl peroxide====
[[File:Benzoyl peroxide gel.jpg|thumb|upright=1.3|alt=A tube of benzoyl peroxide gel|Benzoyl peroxide cream is a common treatment for acne vulgaris.]]

[[Benzoyl peroxide]] (BPO) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly [[dermatitis|skin irritation]]). In the skin follicle, benzoyl peroxide kills ''C. acnes'' by oxidizing its proteins through the formation of oxygen [[free radical]]s and [[benzoic acid]]. These free radicals likely interfere with the bacterium's metabolism and ability to make proteins.<ref name="Leccia2015">{{cite journal | vauthors = Leccia MT, Auffret N, Poli F, Claudel JP, Corvec S, Dreno B | title = Topical acne treatments in Europe and the issue of antimicrobial resistance | journal = Journal of the European Academy of Dermatology and Venereology | volume = 29 | issue = 8 | pages = 1485–92 | date = August 2015 | pmid = 25677763 | doi = 10.1111/jdv.12989 | s2cid = 12894377 | type = Review }}</ref><ref name="Gamble2012"/> Additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation.<ref name="Zaenglein2016">{{cite journal | vauthors = Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R | display-authors = 6 | title = Guidelines of care for the management of acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 74 | issue = 5 | pages = 945–73.e33 | date = May 2016 | pmid = 26897386 | doi = 10.1016/j.jaad.2015.12.037 | type = Review | doi-access = free }}</ref><ref name="Gamble2012">{{cite journal | vauthors = Gamble R, Dunn J, Dawson A, Petersen B, McLaughlin L, Small A, Kindle S, Dellavalle RP | display-authors = 6 | title = Topical antimicrobial treatment of acne vulgaris: an evidence-based review | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 3 | pages = 141–52 | date = June 2012 | pmid = 22268388 | doi = 10.2165/11597880-000000000-00000 | s2cid = 5838346 | type = Review }}</ref> Combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as [[benzoyl peroxide/clindamycin]] and [[benzoyl peroxide/adapalene]], respectively.<ref name=Yin2014/> Topical benzoyl peroxide is effective at treating acne.<ref>{{cite journal | vauthors = Yang Z, Zhang Y, Lazic Mosler E, Hu J, Li H, Zhang Y, Liu J, Zhang Q | display-authors = 6 | title = Topical benzoyl peroxide for acne | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD011154 | date = March 2020 | issue = 3 | pmid = 32175593 | pmc = 7077870 | doi = 10.1002/14651858.CD011154.pub2 | collaboration = Cochrane Skin Group }}</ref>

Side effects include increased [[Photosensitivity#Skin reactions|skin photosensitivity]], dryness, redness, and occasional peeling.<ref name=Benz09>{{cite journal | vauthors = Sagransky M, Yentzer BA, Feldman SR | title = Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris | journal = Expert Opinion on Pharmacotherapy | volume = 10 | issue = 15 | pages = 2555–62 | date = October 2009 | pmid = 19761357 | doi = 10.1517/14656560903277228 | s2cid = 26069784 | type = Review }}</ref> Sunscreen use is often advised during treatment, to prevent [[sunburn]]. Lower concentrations of benzoyl peroxide are just as effective as higher concentrations in treating acne but are associated with fewer side effects.<ref name="Gamble2012"/><ref name="Brandstetter2013">{{cite journal | vauthors = Brandstetter AJ, Maibach HI | title = Topical dose justification: benzoyl peroxide concentrations | journal = The Journal of Dermatological Treatment | volume = 24 | issue = 4 | pages = 275–7 | date = August 2013 | pmid = 22103743 | doi = 10.3109/09546634.2011.641937 | s2cid = 7912384 | type = Review }}</ref> Unlike antibiotics, benzoyl peroxide does not appear to generate [[Antimicrobial resistance|bacterial antibiotic resistance]].<ref name=Benz09/>

====Retinoids====
[[Retinoids]] are medications that reduce inflammation, normalize the follicle [[Cell cycle|cell life cycle]], and reduce sebum production.<ref name=Das2014/><ref name="Riahi2016">{{cite journal | vauthors = Riahi RR, Bush AE, Cohen PR | title = Topical Retinoids: Therapeutic Mechanisms in the Treatment of Photodamaged Skin | journal = American Journal of Clinical Dermatology | volume = 17 | issue = 3 | pages = 265–76 | date = June 2016 | pmid = 26969582 | doi = 10.1007/s40257-016-0185-5 | s2cid = 12663356 | type = Review }}</ref> They are structurally related to [[vitamin A]].<ref name="Riahi2016"/> Studies show dermatologists and primary care doctors underprescribe them for acne.<ref name="Zaenglein2018"/> The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the [[hyperkeratinization|accumulation of skin cells]] within the hair follicle that can create a blockage. They are a first-line acne treatment,<ref name=Vary2015/> especially for people with dark-colored skin. Retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation.<ref name=Yin2014>{{cite journal | vauthors = Yin NC, McMichael AJ | title = Acne in patients with skin of color: practical management | journal = American Journal of Clinical Dermatology | volume = 15 | issue = 1 | pages = 7–16 | date = February 2014 | pmid = 24190453 | doi = 10.1007/s40257-013-0049-1 | s2cid = 43211448 | type = Review }}</ref>

Topical retinoids include [[adapalene]], [[retinol]], [[retinaldehyde]], [[isotretinoin]], [[tazarotene]], [[trifarotene]], and [[tretinoin]].<ref name=Kong2013/><ref name="FDA Snapshot">{{cite web | title=Drug Trials Snapshots: Aklief | website=U.S. [[Food and Drug Administration]] (FDA) | date=11 October 2019 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief | archive-url=https://web.archive.org/web/20191119042107/https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief | archive-date=19 November 2019 | url-status=live | access-date=18 November 2019}}{{PD-notice}}</ref><ref>{{cite web|title=Isotretinoin|url=https://www.drugs.com/international/isotretinoin.html|access-date=2021-04-25|website=Drugs.com|archive-date=16 July 2018|archive-url=https://web.archive.org/web/20180716025017/https://www.drugs.com/international/isotretinoin.html|url-status=live}}</ref> They often cause an initial flare-up of acne and facial [[flushing (physiology)|flushing]] and can cause significant skin irritation. Generally speaking, retinoids increase the skin's [[Photosensitivity|sensitivity to sunlight]] and are therefore recommended for use at night.<ref name=Vary2015/> Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin, whereas adapalene is the least irritating but costs significantly more.<ref name=Vary2015/><ref name=Foti2015>{{cite journal | vauthors = Foti C, Romita P, Borghi A, Angelini G, Bonamonte D, Corazza M | title = Contact dermatitis to topical acne drugs: a review of the literature | journal = Dermatologic Therapy | volume = 28 | issue = 5 | pages = 323–9 | date = September 2015 | pmid = 26302055 | doi = 10.1111/dth.12282 | s2cid = 43870491 | type = Review | doi-access = free }}</ref> Most formulations of tretinoin are incompatible for use with benzoyl peroxide.<ref name="Zaenglein2018"/> Tazarotene is the most effective and expensive topical retinoid but is usually not as well tolerated.<ref name=Vary2015/><ref name=Foti2015/> In 2019 a tazarotene lotion formulation, marketed to be a less irritating option, was approved by the FDA.<ref>{{cite web|title=Arazlo lotion launched in US for acne treatment|url=https://www.healio.com/news/dermatology/20200623/arazlo-lotion-launched-in-us-for-acne-treatment|access-date=2021-03-10|website=Healio.com|archive-date=28 July 2021|archive-url=https://web.archive.org/web/20210728231130/https://www.healio.com/news/dermatology/20200623/arazlo-lotion-launched-in-us-for-acne-treatment|url-status=live}}</ref> Retinol is a form of vitamin A that has similar but milder effects and is present in many over-the-counter moisturizers and other topical products.

Isotretinoin is an oral retinoid that is very effective for severe nodular acne, and moderate acne that is stubborn to other treatments.<ref name="Vary2015" /><ref name="BMJ2013" /> One to two months of use is typically adequate to see improvement. Acne often resolves completely or is much milder after a 4–6&nbsp;month course of oral isotretinoin.<ref name="Vary2015" /> After a single round of treatment, about 80% of people report an improvement, with more than 50% reporting complete remission.<ref name="BMJ2013" /> About 20% of people require a second course, but 80% of those report improvement, resulting in a cumulative 96% efficacy rate.<ref name="BMJ2013" />

There are concerns that isotretinoin is linked to adverse effects, like [[major depressive disorder|depression]], [[suicidality]], and [[anemia]]. There is no clear evidence to support some of these claims.<ref name="Vary2015" /><ref name="BMJ2013" /> Isotretinoin has been found in some studies to be superior to antibiotics or placebo in reducing acne lesions.<ref name="Lew2018"/> However, a 2018 review comparing inflammatory lesions after treatment with antibiotics or isotretinoin found no difference.<ref>{{cite journal | vauthors = Costa CS, Bagatin E, Martimbianco AL, da Silva EM, Lúcio MM, Magin P, Riera R | title = Oral isotretinoin for acne | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD009435 | date = November 2018 | issue = 2 | pmid = 30484286 | pmc = 6383843 | doi = 10.1002/14651858.cd009435.pub2 }}</ref> The frequency of adverse events was about twice as high with isotretinoin use, although these were mostly dryness-related events.<ref name="Lew2018" /> No increased risk of suicide or depression was conclusively found.<ref name="Lew2018" />

Medical authorities strictly regulate isotretinoin use in women of childbearing age due to its known [[teratogenicity|harmful effects in pregnancy]].<ref name="BMJ2013" /> For such a woman to be considered a candidate for isotretinoin, she must have a confirmed negative [[pregnancy test]] and use an effective form of [[contraception|birth control]].<ref name="BMJ2013" /> In 2008, the United States started the [[iPLEDGE]] program to prevent isotretinoin use during pregnancy.<ref name="Tan2016" /> iPLEDGE requires the woman to have two negative pregnancy tests and to use two types of birth control for at least one month before isotretinoin therapy begins and one month afterward.<ref name="Tan2016" /> The effectiveness of the iPLEDGE program is controversial due to continued instances of contraception nonadherence.<ref name="Tan2016">{{cite journal | vauthors = Tan J, Boyal S, Desai K, Knezevic S | title = Oral Isotretinoin: New Developments Relevant to Clinical Practice | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 175–84 | date = April 2016 | pmid = 27015777 | doi = 10.1016/j.det.2015.11.002 | type = Review }}</ref><ref name="Pre2013">{{cite journal | vauthors = Prevost N, English JC | title = Isotretinoin: update on controversial issues | journal = Journal of Pediatric and Adolescent Gynecology | volume = 26 | issue = 5 | pages = 290–3 | date = October 2013 | pmid = 24147278 | doi = 10.1016/j.jpag.2013.05.007 | type = Review }}</ref>

====Antibiotics====
People may apply antibiotics to the skin or take them orally to treat acne. They work by killing ''C. acnes'' and reducing inflammation.<ref name=BMJ2013/><ref name=Benz09/><ref name="Walsh2016">{{cite journal | vauthors = Walsh TR, Efthimiou J, Dréno B | title = Systematic review of antibiotic resistance in acne: an increasing topical and oral threat | journal = The Lancet. Infectious Diseases | volume = 16 | issue = 3 | pages = e23-33 | date = March 2016 | pmid = 26852728 | doi = 10.1016/S1473-3099(15)00527-7 | s2cid = 206154465 | url = http://orca.cf.ac.uk/102767/1/acne.pdf | type = Systematic Review | access-date = 1 January 2019 | archive-url = https://web.archive.org/web/20181105012154/http://orca.cf.ac.uk/102767/1/acne.pdf | archive-date = 5 November 2018 | url-status = live }}</ref> Although multiple guidelines call for healthcare providers to reduce the rates of prescribed oral antibiotics, many providers do not follow this guidance.<ref name="Barbieri2019">{{cite journal | vauthors = Barbieri JS, Spaccarelli N, Margolis DJ, James WD | title = Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 2 | pages = 538–549 | date = February 2019 | pmid = 30296534 | pmc = 6333507 | doi = 10.1016/j.jaad.2018.09.055 | type = Review }}</ref> Oral antibiotics remain the most commonly prescribed systemic therapy for acne.<ref name="Barbieri2019"/> Widespread [[broad-spectrum antibiotic]] overuse for acne has led to higher rates of antibiotic-resistant ''C. acnes'' strains worldwide, especially to the commonly used [[tetracycline]] (e.g., [[doxycycline]]) and macrolide antibiotics (e.g., topical [[erythromycin]]).<ref name="ReferenceA"/><ref name=Benz09/><ref name="Walsh2016"/><ref name="Barbieri2019"/> Therefore, dermatologists prefer antibiotics as part of combination therapy and not for use alone.<ref name="Zaenglein2018"/>

Commonly used antibiotics, either applied to the skin or taken orally, include [[clindamycin]], erythromycin, [[metronidazole]], [[sulfacetamide]], and tetracyclines (e.g., doxycycline or [[minocycline]]).<ref name=Kong2013/> Doxycycline 40 milligrams daily (low-dose) appears to have similar efficacy to 100 milligrams daily and has fewer gastrointestinal side effects.<ref name="Zaenglein2018" /> However, low-dose doxycycline is not FDA-approved for the treatment of acne.<ref>{{cite web|last=Hilton|first=Lisette|date=2019-03-21|title=Dermatologists relying less on antibiotics for acne|url=https://www.dermatologytimes.com/article/dermatologists-relying-less-antibiotics-acne|access-date=2020-06-07|website=Dermatology Times|archive-date=7 June 2020|archive-url=https://web.archive.org/web/20200607011250/https://www.dermatologytimes.com/article/dermatologists-relying-less-antibiotics-acne|url-status=dead}}</ref> Antibiotics applied to the skin are typically used for mild to moderately severe acne.<ref name=BMJ2013/> Oral antibiotics are generally more effective than topical antibiotics and produce faster resolution of inflammatory acne lesions than topical applications.<ref name=Vary2015/> The ''Global Alliance to Improve Outcomes in Acne'' recommends that topical and oral antibiotics are not used together.<ref name="Walsh2016" />

Oral antibiotics are recommended for no longer than three months as antibiotic courses exceeding this duration are associated with the development of antibiotic resistance and show no clear benefit over shorter durations.<ref name="Walsh2016" /> If long-term oral antibiotics beyond three months are used, then it is recommended that benzoyl peroxide or a retinoid be used at the same time to limit the risk of ''C. acnes'' developing antibiotic resistance.<ref name="Walsh2016" />

The antibiotic [[dapsone]] is effective against inflammatory acne when applied to the skin. It is generally not a first-line choice due to its higher cost and a lack of clear superiority over other antibiotics.<ref name=Vary2015/><ref name="Zaenglein2018" /> Topical dapsone is sometimes a preferred therapy in women or for people with sensitive or darker-toned skin.<ref name="Zaenglein2018"/> It is not recommended for use with benzoyl peroxide due to the risk of causing yellow-orange skin discoloration with this combination.<ref name="Aslam2015"/> Minocycline is an effective acne treatment, but it is not a first-line antibiotic due to a lack of evidence that it is better than other treatments, and concerns about its safety compared to other tetracyclines.<ref>{{cite journal | vauthors = Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM | title = Minocycline for acne vulgaris: efficacy and safety | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD002086 | date = August 2012 | volume = 2012 | pmid = 22895927 | doi = 10.1002/14651858.CD002086.pub2 | pmc = 7017847 }}</ref>

[[Sarecycline]] is the most recent oral antibiotic developed specifically for the treatment of acne, and is FDA-approved for the treatment of moderate to severe inflammatory acne in patients nine years of age and older.<ref>{{cite web|title=Prescribing Information for Seysara|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf|access-date=7 June 2020|archive-date=7 June 2020|archive-url=https://web.archive.org/web/20200607011241/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Leyden JJ, Sniukiene V, Berk DR, Kaoukhov A | title = Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study | journal = Journal of Drugs in Dermatology | volume = 17 | issue = 3 | pages = 333–338 | date = March 2018 | pmid = 29537451 | url = http://jddonline.com/articles/dermatology/S1545961618P0333X | access-date = 24 July 2021 | archive-date = 3 August 2021 | archive-url = https://web.archive.org/web/20210803211526/https://jddonline.com/articles/dermatology/S1545961618P0333X | url-status = live }}</ref><ref name=":1">{{cite journal | vauthors = Moore AY, Charles JE, Moore S | title = Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris | journal = Future Microbiology | volume = 14 | pages = 1235–1242 | date = September 2019 | issue = 14 | pmid = 31475868 | pmc = 6802708 | doi = 10.2217/fmb-2019-0199 }}</ref> It is a [[Narrow-spectrum antibiotic|narrow-spectrum]] tetracycline antibiotic that exhibits the necessary antibacterial activity against pathogens related to acne vulgaris and a low propensity for inducing antibiotic resistance.<ref>{{cite journal |journal=PubChem |title=Sarecycline |url=https://pubchem.ncbi.nlm.nih.gov/compound/54681908 |access-date=2020-06-07 |publisher=U.S. National Library of Medicine |archive-date=24 July 2020 |archive-url=https://web.archive.org/web/20200724225741/https://pubchem.ncbi.nlm.nih.gov/compound/54681908 |url-status=live }}</ref><ref>{{cite journal | vauthors = Zhanel G, Critchley I, Lin LY, Alvandi N | title = Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris | journal = Antimicrobial Agents and Chemotherapy | volume = 63 | issue = 1 | date = January 2019 | pmid = 30397052 | pmc = 6325184 | doi = 10.1128/AAC.01297-18 }}</ref> In clinical trials, sarecycline demonstrated clinical efficacy in reducing inflammatory acne lesions as early as three weeks and reduced truncal (back and chest) acne.<ref name=":1" /><ref>{{cite journal | vauthors = Moore A, Green LJ, Bruce S, Sadick N, Tschen E, Werschler P, Cook-Bolden FE, Dhawan SS, Forsha D, Gold MH, Guenthner S, Kempers SE, Kircik LH, Parish JL, Rendon MI, Rich P, Stein-Gold L, Tyring SK, Weiss RA, Nasir A, Schmitz C, Boodhoo TI, Kaoukhov A, Berk DR | display-authors = 6 | title = Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials | journal = Journal of Drugs in Dermatology | volume = 17 | issue = 9 | pages = 987–996 | date = September 2018 | pmid = 30235387 | url = http://jddonline.com/articles/dermatology/S1545961618P0987X | access-date = 24 July 2021 | archive-date = 24 July 2021 | archive-url = https://web.archive.org/web/20210724033025/https://jddonline.com/articles/dermatology/S1545961618P0987X | url-status = live }}</ref>

====Hormonal agents====
In women, the use of [[combined birth control pill]]s can improve acne.<ref name=Tyler2013>{{cite journal | vauthors = Arowojolu AO, Gallo MF, Lopez LM, Grimes DA | veditors = Arowojolu AO | title = Combined oral contraceptive pills for treatment of acne | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD004425 | date = July 2012 | pmid = 22786490 | doi = 10.1002/14651858.CD004425.pub6 | type = Systematic Review & Meta-Analysis | pmc = 11437354 }}</ref> These medications contain an [[estrogen (medication)|estrogen]] and a [[progestin]].<ref name="Kuhl1999" /> They work by decreasing the production of androgen hormones by the ovaries and by decreasing the free and hence biologically active fractions of androgens, resulting in lowered skin production of sebum and consequently reduce acne severity.<ref name="Aslam2015"/><ref name="pmid22994662">{{cite journal | vauthors = Kamangar F, Shinkai K | title = Acne in the adult female patient: a practical approach | journal = International Journal of Dermatology | volume = 51 | issue = 10 | pages = 1162–74 | date = October 2012 | pmid = 22994662 | doi = 10.1111/j.1365-4632.2012.05519.x | s2cid = 5777817 | doi-access = free }}</ref> First-generation progestins such as [[norethindrone]] and [[norgestrel]] have androgenic properties and may worsen acne.<ref name="Zaenglein2018"/> Although oral estrogens decrease IGF-1 levels in some situations, which could theoretically improve acne symptoms,<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | pages = 3–63 | date = August 2005 | issue = Suppl 1 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | access-date = 21 December 2018 | archive-url = https://web.archive.org/web/20160822055012/http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | archive-date = 22 August 2016 | url-status = live }}</ref><ref name="pmid27704479">{{cite journal | vauthors = Duarte FH, Jallad RS, Bronstein MD | title = Estrogens and selective estrogen receptor modulators in acromegaly | journal = Endocrine | volume = 54 | issue = 2 | pages = 306–314 | date = November 2016 | pmid = 27704479 | doi = 10.1007/s12020-016-1118-z | s2cid = 10136018 }}</ref> combined birth control pills do not appear to affect IGF-1 levels in fertile women.<ref name="Kuhl1999">{{cite book |doi=10.1007/978-3-642-60107-1_18 |chapter=Hormonal Contraception |title=Estrogens and Antiestrogens II |series=Handbook of Experimental Pharmacology |year=1999 |last1=Kuhl |first1=H. |volume=135 / 2 |pages=363–407 |isbn=978-3-642-64261-6 }}</ref><ref name="Kuhl1997">{{cite journal |last1=Kuhl |first1=H. |title=Metabolische Effekte der Östrogene und Gestagene |journal=Der Gynäkologe |date=18 April 1997 |volume=30 |issue=4 |pages=357–369 |doi=10.1007/PL00003042 |s2cid=43381309 }}</ref> [[Cyproterone acetate]]-containing birth control pills seem to decrease total and free IGF-1 levels.<ref name="pmid15832490">{{cite journal | vauthors = Wiegratz I, Kuhl H | title = Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives | journal = Treatments in Endocrinology | volume = 1 | issue = 6 | pages = 372–86 | date = 2002 | pmid = 15832490 | doi = 10.2165/00024677-200201060-00003 | s2cid = 71806394 }}</ref> Combinations containing third- or fourth-generation [[progestin]]s, including [[desogestrel]], [[dienogest]], [[drospirenone]], or [[norgestimate]], as well as birth control pills containing cyproterone acetate or [[chlormadinone acetate]], are preferred for women with acne due to their stronger antiandrogenic effects.<ref name="pmid22786490">{{cite journal | vauthors = Arowojolu AO, Gallo MF, Lopez LM, Grimes DA  | veditors = Arowojolu AO | title = Combined oral contraceptive pills for treatment of acne | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD004425 | date = July 2012 | pmid = 22786490 | doi = 10.1002/14651858.CD004425.pub6 | pmc = 11437354 }}</ref><ref name="Powell2017">{{cite journal | vauthors = Powell A | title = Choosing the Right Oral Contraceptive Pill for Teens | journal = Pediatric Clinics of North America | volume = 64 | issue = 2 | pages = 343–358 | date = April 2017 | pmid = 28292450 | doi = 10.1016/j.pcl.2016.11.005 | type = Review }}</ref><ref name="pmid29725277">{{cite journal | vauthors = Słopień R, Milewska E, Rynio P, Męczekalski B | title = Use of oral contraceptives for management of acne vulgaris and hirsutism in women of reproductive and late reproductive age | journal = Przeglad Menopauzalny = Menopause Review | volume = 17 | issue = 1 | pages = 1–4 | date = March 2018 | pmid = 29725277 | pmc = 5925193 | doi = 10.5114/pm.2018.74895 }}</ref> Studies have shown a 40 to 70% reduction in acne lesions with combined birth control pills.<ref name="pmid22994662" /> A 2014 [[systematic review|review]] found that oral antibiotics appear to be somewhat more effective than birth control pills at reducing the number of inflammatory acne lesions at three months.<ref name=Koo2014>{{cite journal | vauthors = Koo EB, Petersen TD, Kimball AB | title = Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 3 | pages = 450–9 | date = September 2014 | pmid = 24880665 | doi = 10.1016/j.jaad.2014.03.051 | type = Systematic Review & Meta-Analysis }}</ref> However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions.<ref name=Koo2014/> The authors of the analysis suggested that birth control pills may be a preferred first-line acne treatment, over oral antibiotics, in certain women due to similar efficacy at six months and a lack of associated antibiotic resistance.<ref name=Koo2014/> In contrast to combined birth control pills, [[progestogen-only birth control]] forms that contain androgenic progestins have been associated with worsened acne.<ref name="Barbieri2019"/>

[[Antiandrogen]]s such as cyproterone acetate and [[spironolactone]] can successfully treat acne, especially in women with signs of excessive androgen production, such as increased [[hirsutism|hairiness]] or skin production of sebum, or [[alopecia|scalp hair loss]].<ref name="Aslam2015"/><ref name=Kong2013/> Spironolactone is an effective treatment for acne in adult women.<ref name="pmid28155090" /><ref>{{cite journal |last1=Santer |first1=Miriam |last2=Lawrence |first2=Megan |last3=Renz |first3=Susanne |last4=Eminton |first4=Zina |last5=Stuart |first5=Beth |last6=Sach |first6=Tracey H |last7=Pyne |first7=Sarah |last8=Ridd |first8=Matthew J |last9=Francis |first9=Nick |last10=Soulsby |first10=Irene |last11=Thomas |first11=Karen |last12=Permyakova |first12=Natalia |last13=Little |first13=Paul |last14=Muller |first14=Ingrid |last15=Nuttall |first15=Jacqui |date=2023-05-16 |title=Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial |journal=The BMJ |volume=381|pages=e074349 |doi=10.1136/bmj-2022-074349 |pmid=37192767 |pmc=10543374 |s2cid=258717921 |issn=1756-1833|doi-access=free }}</ref> Unlike combined birth control pills, it is not approved by the United States [[Food and Drug Administration]] for this purpose.<ref name=Vary2015/><ref name=Yin2014/><ref name="pmid28155090">{{cite journal | vauthors = Layton AM, Eady EA, Whitehouse H, Del Rosso JQ, Fedorowicz Z, van Zuuren EJ | title = Oral Spironolactone for Acne Vulgaris in Adult Females: A Hybrid Systematic Review | journal = American Journal of Clinical Dermatology | volume = 18 | issue = 2 | pages = 169–191 | date = April 2017 | pmid = 28155090 | pmc = 5360829 | doi = 10.1007/s40257-016-0245-x }}</ref> Spironolactone is an [[aldosterone antagonist]] and is a useful acne treatment due to its ability to additionally block the [[androgen receptor]] at higher doses.<ref name=Yin2014/><ref name="Barbieri2019"/> Alone or in combination with a birth control pill, spironolactone has shown a 33 to 85% reduction in acne lesions in women.<ref name="pmid22994662" /> The effectiveness of spironolactone for acne appears to be dose-dependent.<ref name="pmid22994662" /> High-dose cyproterone acetate alone reportedly decreases acne symptoms in women by 75 to 90% within three months.<ref name="pmid25627824" /> It is usually combined with an estrogen to avoid [[menstrual irregularities]] and [[estrogen deficiency]].<ref name="pmid9856417">{{cite journal | vauthors = Diamanti-Kandarakis E | title = How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome? | journal = Journal of Endocrinological Investigation | volume = 21 | issue = 9 | pages = 623–9 | date = October 1998 | pmid = 9856417 | doi = 10.1007/BF03350788 | s2cid = 46484837 }}</ref> The medication appears to be effective in the treatment of acne in males, with one study finding that a high dosage reduced inflammatory acne lesions by 73%.<ref name="WardBrogden1984">{{cite journal | vauthors = Ward A, Brogden RN, Heel RC, Speight TM, Avery GS | title = Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders | journal = Drugs | volume = 28 | issue = 1 | pages = 6–37 | date = July 1984 | pmid = 6235105 | doi = 10.2165/00003495-198428010-00002 }}</ref><ref name="Rasmusson1986">{{cite book |doi=10.1016/S0065-7743(08)61128-8 |title=Chapter 18. Chemical Control of Androgen Action |series=Annual Reports in Medicinal Chemistry |year=1986 |last1=Rasmusson |first1=Gary H. |volume=21 |pages=179–188 |isbn=9780120405213 }}</ref> However, spironolactone and cyproterone acetate's side effects in males, such as [[gynecomastia]], [[sexual dysfunction]], and decreased [[bone mineral density]], generally make their use for male acne impractical.<ref name="WardBrogden1984" /><ref name="Rasmusson1986" /><ref name="pmid19297634">{{cite journal | vauthors = Giltay EJ, Gooren LJ | title = Potential side effects of androgen deprivation treatment in sex offenders | journal = The Journal of the American Academy of Psychiatry and the Law | volume = 37 | issue = 1 | pages = 53–8 | date = 2009 | pmid = 19297634 }}</ref>

Pregnant and lactating women should not receive antiandrogens for their acne due to a possibility of [[congenital disorder|birth disorders]] such as [[hypospadias]] and [[Feminization (biology)|feminization]] of male babies.<ref name=Kong2013/> Women who are sexually active and who can or may become pregnant should use an effective method of contraception to prevent pregnancy while taking an antiandrogen.<ref name="pmid30312645" /> Antiandrogens are often combined with birth control pills for this reason, which can result in additive efficacy.<ref name=Yin2014 /><ref name="pmid25896771">{{cite journal | vauthors = Oudenhoven MD, Kinney MA, McShane DB, Burkhart CN, Morrell DS | title = Adverse effects of acne medications: recognition and management | journal = American Journal of Clinical Dermatology | volume = 16 | issue = 4 | pages = 231–242 | date = August 2015 | pmid = 25896771 | doi = 10.1007/s40257-015-0127-7 | s2cid = 37512606 }}</ref> The FDA added a [[Boxed warning|black-box warning]] to spironolactone about possible [[tumor]] risks based on [[preclinical research]] with very high doses (>100-fold clinical doses) and cautioned that unnecessary use of the medication should be avoided.<ref name="Zaenglein2016"/><ref name="Barbieri2019" /><ref>{{cite web|title=FDA. Prescribing Information|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/012151s062lbl.pdf|access-date=7 June 2020|archive-date=24 August 2020|archive-url=https://web.archive.org/web/20200824235422/https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/012151s062lbl.pdf|url-status=live}}</ref> However, several large [[epidemiological study|epidemiological studies]] subsequently found no greater risk of tumors in association with spironolactone in humans.<ref name="Barbieri2019" /><ref name="pmid30467659">{{cite journal | vauthors = Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture ME | title = Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies | journal = Breast Cancer Res. Treat. | volume = 174 | issue = 1 | pages = 15–26 | date = February 2019 | pmid = 30467659 | pmc = 6773272 | doi = 10.1007/s10549-018-4996-3 }}</ref><ref name="pmid28979664">{{cite journal | vauthors = Endly DC, Miller RA | title = Oily Skin: A review of Treatment Options | journal = J Clin Aesthet Dermatol | volume = 10 | issue = 8 | pages = 49–55 | date = August 2017 | pmid = 28979664 | pmc = 5605215 }}</ref><ref name="pmid32738426">{{cite journal | vauthors = Heymann WR | title = Spironolactone and breast cancer: Fear not! | journal = J. Am. Acad. Dermatol. | date = July 2020 | volume = 83 | issue = 4 | pages = 1008–1009 | pmid = 32738426 | doi = 10.1016/j.jaad.2020.07.104 | s2cid = 220924754 }}</ref> Conversely, strong associations of cyproterone acetate with certain [[brain tumor]]s have been discovered and its use has been restricted.<ref name="SenofontePallotti2020">{{cite journal |last1=Senofonte |first1=Giulia |last2=Pallotti |first2=Francesco |last3=Lombardo |first3=Francesco |title=Ciproterone acetato e meningiomi: lo stato dell'arte |trans-title=Cyproterone acetate and meningiomas: the state of the art |language=it |journal=L'Endocrinologo |date=June 2020 |volume=21 |issue=3 |pages=171–175 |doi=10.1007/s40619-020-00746-8 |doi-access=free |hdl=11573/1492686 |hdl-access=free }}</ref><ref name="pmid32419942">{{cite journal | vauthors = Kohl S | title = Council of Europe resolution to promote pharmaceutical care in Europe | journal = Eur J Hosp Pharm | volume = 27 | issue = 3 | pages = 184–188 | date = May 2020 | pmid = 32419942 | doi = 10.1136/ejhpharm-2020-002305 | pmc = 7223358 }}</ref><ref name="pmid33536184">{{cite journal | vauthors = Weill A, Nguyen P, Labidi M, Cadier B, Passeri T, Duranteau L, Bernat AL, Yoldjian I, Fontanel S, Froelich S, Coste J | title = Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study | journal = The BMJ | volume = 372 | pages = n37 | date = February 2021 | pmid = 33536184 | doi = 10.1136/bmj.n37 | doi-access = free }}</ref> The brain tumor risk with cyproterone acetate is due to its strong [[progestogen (medication)|progestogenic]] actions and is not related to antiandrogenic activity nor shared by other antiandrogens.<ref name="SenofontePallotti2020" /><ref name="pmid32705456">{{cite journal | vauthors = Apra C, Roblot P, Alkhayri A, Le Guérinel C, Polivka M, Chauvet D | title = Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas | journal = J. Neurooncol. | date = July 2020 | volume = 149 | issue = 1 | pages = 95–101 | pmid = 32705456 | doi = 10.1007/s11060-020-03576-8 | s2cid = 220720801 | url = https://hal.sorbonne-universite.fr/hal-03270880/file/Apra%20et%20al.%20-%202020%20-%20Female%20gender%20and%20exogenous%20progesterone%20expositio.pdf | access-date = 18 August 2021 | archive-date = 4 September 2021 | archive-url = https://web.archive.org/web/20210904051802/https://hal.sorbonne-universite.fr/hal-03270880/file/Apra%20et%20al.%20-%202020%20-%20Female%20gender%20and%20exogenous%20progesterone%20expositio.pdf | url-status = live }}</ref><ref name="pmid33536184" />

[[Flutamide]], a pure [[receptor antagonist|antagonist]] of the androgen receptor, is effective in treating acne in women.<ref name="pmid25627824">{{cite journal | vauthors = Bettoli V, Zauli S, Virgili A | title = Is hormonal treatment still an option in acne today? | journal = The British Journal of Dermatology | volume = 172 | pages = 37–46 | date = July 2015 | issue = Suppl 1 | pmid = 25627824 | doi = 10.1111/bjd.13681 | s2cid = 35615492 | doi-access =  }}</ref><ref name="pmid25845307">{{cite journal | vauthors = Husein-ElAhmed H | title = Management of acne vulgaris with hormonal therapies in adult female patients | journal = Dermatologic Therapy | volume = 28 | issue = 3 | pages = 166–72 | year = 2015 | pmid = 25845307 | doi = 10.1111/dth.12231 | s2cid = 2628354 | doi-access = free }}</ref> It appears to reduce acne symptoms by 80 to 90% even at low doses, with several studies showing complete acne clearance.<ref name="pmid25627824" /><ref name="pmid28562419">{{cite journal | vauthors = Nguyen HL, Tollefson MM | title = Endocrine disorders and hormonal therapy for adolescent acne | journal = Current Opinion in Pediatrics | volume = 29 | issue = 4 | pages = 455–465 | date = August 2017 | pmid = 28562419 | doi = 10.1097/MOP.0000000000000515 | s2cid = 4640778 }}</ref><ref name="pmid10495361">{{cite journal | vauthors = Diamanti-Kandarakis E | title = Current aspects of antiandrogen therapy in women | journal = Current Pharmaceutical Design | volume = 5 | issue = 9 | pages = 707–23 | date = September 1999 | doi = 10.2174/1381612805666230111201150 | pmid = 10495361 | url = https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA707 | access-date = 21 December 2018 | archive-url = https://web.archive.org/web/20200227012541/https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA707 | archive-date = 27 February 2020 | url-status = live }}</ref> In one study, flutamide decreased acne scores by 80% within three months, whereas spironolactone decreased symptoms by only 40% in the same period.<ref name="pmid10495361" /><ref name="ShelleyShelley2001">{{cite book|first1=Walter Brown|last1=Shelley|first2=E. Dorinda|last2=Shelley|title=Advanced Dermatologic Therapy II|url=https://books.google.com/books?id=vuJsAAAAMAAJ|year=2001|publisher=W. B. Saunders|isbn=978-0-7216-8258-7|access-date=21 December 2018|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111121854/https://books.google.com/books?id=vuJsAAAAMAAJ|url-status=live}}</ref><ref name="BalenFranks2010">{{cite book | first1 = Adam | last1 = Balen | first2 = Stephen | last2 = Franks | first3 = Roy | last3 = Homburg | first4 = Sean | last4 = Kehoe | title = Current Management of Polycystic Ovary Syndrome | url = https://books.google.com/books?id=0rtUBAAAQBAJ&pg=PA132 | date = October 2010 | publisher = Cambridge University Press | isbn = 978-1-906985-41-7 | pages = 132– | access-date = 21 December 2018 | archive-date = 11 January 2023 | archive-url = https://web.archive.org/web/20230111121859/https://books.google.com/books?id=0rtUBAAAQBAJ&pg=PA132 | url-status = live }}</ref> In a large long-term study, 97% of women reported satisfaction with the control of their acne with flutamide.<ref name="pmid28492054">{{cite journal | vauthors = Trivedi MK, Shinkai K, Murase JE | title = A Review of hormone-based therapies to treat adult acne vulgaris in women | journal = International Journal of Women's Dermatology | volume = 3 | issue = 1 | pages = 44–52 | date = March 2017 | pmid = 28492054 | pmc = 5419026 | doi = 10.1016/j.ijwd.2017.02.018 }}</ref> Although effective, flutamide has a risk of serious [[liver toxicity]], and cases of death in women taking even low doses of the medication to treat androgen-dependent skin and hair conditions have occurred.<ref name="pmid28379593">{{cite journal | vauthors = Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A | title = Flutamide-induced hepatotoxicity: ethical and scientific issues | journal = European Review for Medical and Pharmacological Sciences | volume = 21 | issue = 1 Suppl | pages = 69–77 | date = March 2017 | pmid = 28379593 }}</ref> As such, the use of flutamide for acne has become increasingly limited,<ref name="pmid28492054" /><ref name="YasaDural2016">{{cite journal |last1=Yasa |first1=Cenk |last2=Dural |first2=Özlem |last3=Bastu |first3=Ercan |last4=Uğurlucan |first4=Funda Güngör |title=Hirsutism, Acne, and Hair Loss: Management of Hyperandrogenic Cutaneous Manifestations of Polycystic Ovary Syndrome |journal=Gynecology Obstetrics & Reproductive Medicine |date=22 August 2017 |volume=23 |issue=2 |pages=110–119 |doi=10.21613/GORM.2016.613 |doi-access=free }}</ref><ref name="pmid28274354">{{cite journal | vauthors = Barros B, Thiboutot D | title = Hormonal therapies for acne | journal = Clinics in Dermatology | volume = 35 | issue = 2 | pages = 168–172 | date = 2017 | pmid = 28274354 | doi = 10.1016/j.clindermatol.2016.10.009 }}</ref> and it has been argued that continued use of flutamide for such purposes is unethical.<ref name="pmid28379593" /> [[Bicalutamide]], a pure androgen receptor antagonist with the same mechanism as flutamide and with comparable or superior antiandrogenic [[efficacy]] but with a far lower risk of liver toxicity, is an alternative option to flutamide in the treatment of androgen-dependent skin and hair conditions in women.<ref name="pmid30312645">{{cite journal | vauthors = Azarchi S, Bienenfeld A, Lo Sicco K, Marchbein S, Shapiro J, Nagler AR | title = Androgens in women: Hormone-modulating therapies for skin disease | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 6 | pages = 1509–1521 | date = June 2019 | pmid = 30312645 | doi = 10.1016/j.jaad.2018.08.061 | s2cid = 52973096 }}</ref><ref name="pmid8717470">{{cite journal | vauthors = Blackledge GR | title = Clinical progress with a new antiandrogen, Casodex (bicalutamide) | journal = European Urology | volume = 29 Suppl 2 | issue = 2 | pages = 96–104 | date = 1996 | pmid = 8717470 | doi = 10.1159/000473847 }}</ref><ref name="pmid14748655">{{cite journal | vauthors = Fradet Y | title = Bicalutamide (Casodex) in the treatment of prostate cancer | journal = Expert Review of Anticancer Therapy | volume = 4 | issue = 1 | pages = 37–48 | date = February 2004 | pmid = 14748655 | doi = 10.1586/14737140.4.1.37 | s2cid = 34153031 }}</ref><ref name="pmid27416311">{{cite journal | vauthors = Hassoun LA, Chahal DS, Sivamani RK, Larsen LN | title = The use of hormonal agents in the treatment of acne | journal = Seminars in Cutaneous Medicine and Surgery | volume = 35 | issue = 2 | pages = 68–73 | date = June 2016 | pmid = 27416311 | doi = 10.12788/j.sder.2016.027 | doi-broken-date = 21 December 2024 }}</ref>

[[Clascoterone]] is a [[topical administration|topical]] antiandrogen that has demonstrated effectiveness in the treatment of acne in both males and females and was approved for clinical use for this indication in August 2020.<ref name="Winlevi FDA label">{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213433s000lbl.pdf | title=Winlevi (clascoterone) cream, for topical use | publisher=Cassiopea | access-date=9 September 2020 | archive-date=18 September 2020 | archive-url=https://web.archive.org/web/20200918114726/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213433s000lbl.pdf | url-status=live }}</ref><ref name="pmid30466681">{{cite journal | vauthors = Marson JW, Baldwin HE | title = New Concepts, Concerns, and Creations in Acne | journal = Dermatologic Clinics | volume = 37 | issue = 1 | pages = 1–9 | date = January 2019 | pmid = 30466681 | doi = 10.1016/j.det.2018.07.002 | s2cid = 53718051 | type = Review }}</ref><ref name="Timmins2018">{{cite journal | title = Industry update: the latest developments in the field of therapeutic delivery, July 2018 | journal = Therapeutic Delivery | volume = 9 | issue = 11 | pages = 797–809 | year = 2018 | doi = 10.4155/tde-2018-0055 | type = Review | last1 = Timmins | first1 = Peter| doi-access = free }}</ref><ref name="pmid29594974">{{cite journal | vauthors = Trivedi MK, Bosanac SS, Sivamani RK, Larsen LN | title = Emerging Therapies for Acne Vulgaris | journal = American Journal of Clinical Dermatology | volume = 19 | issue = 4 | pages = 505–516 | date = August 2018 | pmid = 29594974 | doi = 10.1007/s40257-018-0345-x | s2cid = 4398912 | type = Review }}</ref><ref name="pmid29872679">{{cite journal | vauthors = Tan AU, Schlosser BJ, Paller AS | title = A review of diagnosis and treatment of acne in adult female patients | journal = International Journal of Women's Dermatology | volume = 4 | issue = 2 | pages = 56–71 | date = June 2018 | pmid = 29872679 | pmc = 5986265 | doi = 10.1016/j.ijwd.2017.10.006 | type = Review }}</ref> It has shown no systemic absorption or associated antiandrogenic side effects.<ref name="pmid29594974" /><ref name="pmid29872679" /><ref name="pmid25474485">{{cite journal | vauthors = Aslam I, Fleischer A, Feldman S | title = Emerging drugs for the treatment of acne | journal = Expert Opinion on Emerging Drugs | volume = 20 | issue = 1 | pages = 91–101 | date = March 2015 | pmid = 25474485 | doi = 10.1517/14728214.2015.990373 | s2cid = 12685388 }}</ref> In a small direct head-to-head comparison, clascoterone showed greater effectiveness than topical isotretinoin.<ref name="pmid29594974" /><ref name="pmid29872679" /><ref name="pmid25474485" /> [[5α-Reductase inhibitor]]s such as [[finasteride]] and [[dutasteride]] may be useful for the treatment of acne in both males and females but have not been adequately evaluated for this purpose.<ref name=Vary2015/><ref name="pmid23377402">{{cite journal | vauthors = Azzouni F, Zeitouni N, Mohler J | url = https://jddonline.com/articles/dermatology/S1545961613E0030X | title = Role of 5α-reductase inhibitors in androgen-stimulated skin disorders | journal = Journal of Drugs in Dermatology | volume = 12 | issue = 2 | pages = e30-5 | date = February 2013 | pmid = 23377402 | access-date = 31 August 2020 | archive-date = 9 August 2020 | archive-url = https://web.archive.org/web/20200809085939/https://jddonline.com/articles/dermatology/S1545961613E0030X | url-status = live }}</ref><ref name="Danby2015">{{cite book|first=F. William|last=Danby|title=Acne: Causes and Practical Management|url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|date=27 January 2015|publisher=John Wiley & Sons|isbn=978-1-118-23277-4|pages=147–|access-date=21 December 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031704/https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|url-status=live}}</ref><ref name="pmid23431485">{{cite journal | vauthors = Marchetti PM, Barth JH | title = Clinical biochemistry of dihydrotestosterone | journal = Annals of Clinical Biochemistry | volume = 50 | issue = Pt 2 | pages = 95–107 | date = March 2013 | pmid = 23431485 | doi = 10.1258/acb.2012.012159 | s2cid = 8325257 | doi-access = free }}</ref> Moreover, 5α-reductase inhibitors have a strong potential for producing birth defects in male babies and this limits their use in women.<ref name=Vary2015/><ref name="Danby2015" /> However, 5α-reductase inhibitors are frequently used to treat [[hirsutism|excessive facial/body hair]] in women and can be combined with birth control pills to prevent pregnancy.<ref name="pmid23377402" /> There is no evidence as of 2010 to support the use of [[cimetidine]] or [[ketoconazole]] in the treatment of acne.<ref name="pmid20082945">{{cite journal | vauthors = Katsambas AD, Dessinioti C | title = Hormonal therapy for acne: why not as first line therapy? facts and controversies | journal = Clinics in Dermatology | volume = 28 | issue = 1 | pages = 17–23 | date = 2010 | pmid = 20082945 | doi = 10.1016/j.clindermatol.2009.03.006 }}</ref>

Hormonal treatments for acne such as combined birth control pills and antiandrogens may be considered first-line therapy for acne under many circumstances, including desired contraception, known or suspected hyperandrogenism, acne during adulthood, acne that flares premenstrually, and when symptoms of significant sebum production (seborrhea) are co-present.<ref name="pmid20082945" /> Hormone therapy is effective for acne both in women with hyperandrogenism and in women with normal androgen levels.<ref name="pmid20082945" />

====Azelaic acid====
{{Self-contradictory|section|about=efficacy|date=December 2023}}
[[Azelaic acid]] is effective for mild to moderate acne when applied topically at a 15–20% concentration.<ref name=Sieber2014/><ref name=Pugashetti2013/><ref>{{cite journal |last1=Gollnick |first1=Harald P. M. |last2=Graupe |first2=Klaus |last3=Zaumseil |first3=Rolf-Peter |title=15% Azelainsauregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien. [[Azelaic acid]] 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies |journal=Journal der Deutschen Dermatologischen Gesellschaft |date=October 2004 |volume=2 |issue=10 |pages=841–847 |doi=10.1046/j.1439-0353.2004.04731.x |pmid=16281587 |s2cid=58809558 }}</ref><ref>{{cite journal |last1=Thiboutot |first1=D |title=Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris |journal=Journal of Drugs in Dermatology |date=January 2008 |volume=7 |issue=1 |pages=13–6 |pmid=18246693 }}</ref> Treatment twice daily for six months is necessary, and is as effective as topical benzoyl peroxide&nbsp;5%, isotretinoin&nbsp;0.05%, and erythromycin&nbsp;2%.<ref name=Herb2010>{{cite journal | vauthors = Morelli V, Calmet E, Jhingade V | title = Alternative therapies for common dermatologic disorders, part 2 | journal = Primary Care | volume = 37 | issue = 2 | pages = 285–96 | date = June 2010 | pmid = 20493337 | doi = 10.1016/j.pop.2010.02.005 | type = Review }}</ref> Azelaic acid is an effective acne treatment due to its ability to reduce skin cell accumulation in the follicle and its [[antibacterial]] and [[anti-inflammation|anti-inflammatory]] properties.<ref name=Sieber2014/> It has a slight skin-lightening effect due to its ability to inhibit melanin synthesis. Therefore, it is useful in treating individuals with acne who are also affected by post-inflammatory hyperpigmentation.<ref name=Vary2015/> Azelaic acid may cause skin irritation.<ref>{{MedlinePlusEncyclopedia|603020|Azelaic Acid Topical}}</ref> It is less effective and more expensive than retinoids.<ref name=Vary2015/> Azelaic acid also led to worse treatment response when compared to benzoyl peroxide. When compared to tretinoin, azelaic acid makes little or no treatment response.<ref>{{cite journal |last1=Liu |first1=Haibo |last2=Yu |first2=Haiyan |last3=Xia |first3=Jun |last4=Liu |first4=Ling |last5=Liu |first5=Guan J |last6=Sang |first6=Hong |last7=Peinemann |first7=Frank |date=2020-05-01 |editor-last=Cochrane Skin Group |title=Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne |journal=Cochrane Database of Systematic Reviews |volume=5 |issue=5 |pages=CD011368 |doi=10.1002/14651858.CD011368.pub2 |pmc=7193765 |pmid=32356369}}</ref>

====Salicylic acid====
[[Salicylic acid]] is a topically applied [[beta-hydroxy acid]] that [[Bacteriostatic agent|stops bacteria from reproducing]] and has keratolytic properties.<ref name=Madan2014/><ref name=Well2013>{{cite journal | vauthors = Well D | title = Acne vulgaris: A review of causes and treatment options | journal = The Nurse Practitioner | volume = 38 | issue = 10 | pages = 22–31; quiz 32 | date = October 2013 | pmid = 24048347 | doi = 10.1097/01.NPR.0000434089.88606.70 | type = Review | doi-access = free }}</ref> It is less effective than retinoid therapy.<ref name=BMJ2013/> Salicylic acid opens obstructed skin pores and promotes the shedding of epithelial skin cells.<ref name=Madan2014>{{cite journal | vauthors = Madan RK, Levitt J | title = A review of toxicity from topical salicylic acid preparations | journal = Journal of the American Academy of Dermatology | volume = 70 | issue = 4 | pages = 788–792 | date = April 2014 | pmid = 24472429 | doi = 10.1016/j.jaad.2013.12.005 | type = Review }}</ref> [[Xerosis|Dry skin]] is the most commonly seen side effect with topical application, though [[hyperpigmentation|darkening]] of the skin can occur in individuals with darker skin types.<ref name=Vary2015/>

====Other medications====
Topical and oral preparations of [[nicotinamide]] (the [[amide]] form of [[Niacin (nutrient)|vitamin B<sub>3</sub>]]) are alternative medical treatments.<ref name=Rolfe2014>{{cite journal | vauthors = Rolfe HM | title = A review of nicotinamide: treatment of skin diseases and potential side effects | journal = Journal of Cosmetic Dermatology | volume = 13 | issue = 4 | pages = 324–8 | date = December 2014 | pmid = 25399625 | doi = 10.1111/jocd.12119 | s2cid = 28160151 | type = Review }}</ref> Nicotinamide reportedly improves acne due to its anti-inflammatory properties<ref name=Rolfe2014/> (influencing neutrophil [[chemotaxis]], inhibiting the release of histamine, suppressing the lymphocyte transformation test, and reducing nitric oxide synthase production induced by cytokines),<ref name="pmid38725769"/> its ability to suppress sebum production, and its wound healing properties.<ref name=Rolfe2014/> Topical and oral preparations of zinc are suggested treatments for acne; evidence to support their use for this purpose is limited.<ref name=Brandt2013>{{cite journal | vauthors = Brandt S | title = The clinical effects of zinc as a topical or oral agent on the clinical response and pathophysiologic mechanisms of acne: a systematic review of the literature | journal = Journal of Drugs in Dermatology | volume = 12 | issue = 5 | pages = 542–5 | date = May 2013 | pmid = 23652948 | type = Review }}</ref> Zinc's capacities to reduce inflammation and sebum production as well as inhibit ''C. acnes'' growth are its proposed mechanisms for improving acne.<ref name=Brandt2013/> [[Antihistamines]] may improve symptoms among those already taking isotretinoin due to their anti-inflammatory properties and their ability to suppress sebum production.<ref name=DC2016>{{cite journal | vauthors = Layton AM | title = Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 147–57 | date = April 2016 | pmid = 27015774 | doi = 10.1016/j.det.2015.11.008 | type = Review }}</ref>

[[Hydroquinone]] lightens the skin when applied topically by inhibiting [[tyrosinase]], the enzyme responsible for converting the amino acid [[tyrosine]] to the skin pigment [[melanin]], and is used to treat acne-associated post-inflammatory hyperpigmentation.<ref name="Chandra2012"/> By interfering with the production of melanin in the [[epidermis]], hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time.<ref name="Chandra2012"/> Improvement in skin [[hyperpigmentation]] is typically seen within six months when used twice daily. Hydroquinone is ineffective for hyperpigmentation affecting deeper layers of skin such as the [[dermis]].<ref name="Chandra2012"/> The use of a [[sunscreen]] with [[Sun protection factor|SPF]]&nbsp;15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone.<ref name="Chandra2012"/> Its application only to affected areas lowers the risk of lightening the color of normal skin but can lead to a temporary ring of lightened skin around the hyperpigmented area.<ref name="Chandra2012"/> Hydroquinone is generally well-tolerated; side effects are typically mild (e.g., skin irritation) and occur with the use of a higher than the recommended 4% concentration.<ref name="Chandra2012"/> Most preparations contain the preservative [[sodium metabisulfite]], which has been linked to rare cases of [[allergic reaction]]s, including [[anaphylaxis]] and severe [[asthma]] exacerbations in susceptible people.<ref name="Chandra2012"/> In extremely rare cases, the frequent and improper application of high-dose hydroquinone has been associated with a systemic condition known as [[exogenous ochronosis]] (skin discoloration and [[connective tissue]] damage from the accumulation of [[homogentisic acid]]).<ref name="Chandra2012"/>

====Combination therapy====
Combination therapy—using medications of different classes together, each with a different mechanism of action—has been demonstrated to be a more effective approach to acne treatment than monotherapy.<ref name="Aslam2015"/><ref name=Kong2013/> The use of topical benzoyl peroxide and [[antibiotic]]s together is more effective than antibiotics alone.<ref name="Aslam2015"/> Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone.<ref name="Aslam2015"/> Frequently used combinations include the following: antibiotic and benzoyl peroxide, antibiotic and topical retinoid, or topical retinoid and benzoyl peroxide.<ref name=Kong2013/> Dermatologists generally prefer combining benzoyl peroxide with a retinoid over the combination of a topical antibiotic with a retinoid. Both regimens are effective, but benzoyl peroxide does not lead to antibiotic resistance.<ref name="Aslam2015"/>