Hirsutism medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

Pharmacologic medical therapies for hirsituism include oral contraceptives, androgen receptor blockers, 5-alpha reductase inhibitors, gonadotrophin-releasing hormone (GnRH agonist), adrenal suppressive glucocorticoids, insulin-sensitising agents, and biological modifiers of hair follicular growth. Treatment options are systemic therapy and topical therapy.

Medical Therapy

Pharmacologic medical therapies for hirsituism include:^[1]
- Oral contraceptives
- Androgen receptor blockers
- 5-alpha reductase inhibitors
- Gonadotrophin-releasing hormone (GnRH agonist)
- Adrenal suppressive glucocorticoids
- Insulin-sensitising agents
- Biological modifiers of hair follicular growth

Hirsutism

1. Adult
- 1.1 Systemic therapy
  - Preferred regimen (1): Ethinyl estradiol 30 μg PLUS norethindrone 1 mg PO daily over a 9-month period^[2]
  - Preferred regimen (2): Mestranol 100 μg PLUS norethindrone 2 mg PO daily for about 2 weeks^[3]
  - Preferred regimen (3): Ethinyl estradiol 30 μg PLUS desogestrel 150 mcg PO daily for 4-7 months^[4]
  - Preferred regimen (4): Spironolactone starting dose of 50 mg PO q12h; may be increased to 200 mg PO daily.^[5]
  - Alternative regimen (1): Cyproterone Acetate 50-100 mg PO daily^[6]
  - Alternative regimen (2): Cyproterone Acetate 2 mg PLUS ethinyl estradiol 35 μg PO daily^[7]
  - Alternative regimen (3): Finasteride 1-5 mg PO daily^[8]
  - Alternative regimen (4): Flutamide 125-250 mg PO q12h
  - Alternative regimen (5): Bicalutamide 25 mg PO daily^[9]
  - Alternative regimen (6): Metformin 500-1000 mg PO q12h^[10]
  - Alternative regimen (7): Rosiglitazone 4-8 mg PO daily
  - Alternative regimen (8): Pioglitazone 10-30 mg PO daily^[11]
  - Alternative regimen (9): Leuprolide 7.5 mg IM PLUS estradiol 25-50 µg transdermal monthly^[12]
  - Alternative regimen (10): Prednisone 5-10 mg PO daily^[13]
- 1.2 Topical Therapy
  - Preferred regimen (1): Eflornithine hydrochloride 13.9% cream topical q12h^[14]
  - Preferred regimen (2): Finasteride 0.25% or 0.5% cream topical daily^[15]

Group	Medicine	Dosage	Mechanism of action	Side effect	Notes
Oral Contraceptive Pills (OCPs)	Ethinyl estradiol/ Norethindrone	30 μg / 1.0 mg	Inhibiting androgen secretion by the ovaries Increasing sex hormone binding globulin (SHBG) production by the liver Inhibiting adrenal androgen production	Increased risk of venous thromboembolism Breast tenderness Headache Gastrointestinal symptoms	Absolute contraindications Smoking over the age of 35 (>15 cigarettes per day) Hypertension Ischemic heart disease Migraine headache with focal neurological symptoms Breast cancer (current) Diabetes with retinopathy/nephropathy/neuropathy Severe cirrhosis Liver tumour (adenoma or hepatoma)
	Mestranol/norethindrone	100 μg / 2mg
	Ethinyl estradiol/ desogestrel	30 μg / 150 mcg
Antiandrogens	Spironolactone	100-200 mg	Antagonist of both aldosterone and androgen receptor Competes with dihydrotestosterone (DHT) for binding to the androgen receptor Variable progestational activity Decreases production of ovarian androgens Inhibitory effect on 5 alpha-reductase activity (5-RA) Competes with androgens for binding to SHBG	Irregular menstrual bleeding Headache Hypotension Nausea Decreased libido	Contraindications Renal insufficiency Hyperkalaemia
	Cyproterone Acetate	50-100 mg	Competes with dihydrotestosterone for the androgen receptor Inhibits 5α-reductase Decrease in circulating testosterone and androstenedione levels through a reduction in circulating luteinizing hormone (LH)	Liver toxicity Irregular menstrual bleeding Nausea Decreased libido	–
	Cyproterone Acetate/ ethinyl estradiol	2 mg / 35 μg			–
	Flutamide	125-250 mg	Non-steroidal, competitive inhibitors of androgen receptor binding	Hepatotoxicity Fulminant liver failure	Contraindication Fulminant liver failure
	Bicalutamide	25 mg		Hepatotoxicity Fulminant liver failure	Contraindication Fulminant liver failure
5-alpha reductase inhibitors	Finasteride	1-5 mg	Type II inhibitor of the 5α-reductase enzyme Reduces the conversion of testosterone into dihydrotestosterone	Feminisation of the male fetus Liver dysfunction	–
5-alpha reductase inhibitors	Dutasteride	0.5 mg		Feminisation of the male fetus Liver dysfunction	–
Gonadotrophin-releasing hormone (GnRH agonist)	Leuprolide	7.5 mg	Suppress the hypothalamic-pituitary-ovarian axis Inhibiting luteinising hormone (LH) and follicle-stimulating hormone (FSH) Decreasing the secretion of androgens by the ovaries	If not combined with estrogen Menopausal symptoms Hot flushes Osteoporosis	GnRH analogues not suggested for most women with hirsutism, because of: Not seem to have advantages over other therapies High price Need additional estrogen to prevent bone loss and menopausal symptoms
Adrenal suppressive glucocorticoids	Prednisone	5-10 mg	Used in cases of non-classic congenital adrenal hyperplasia Suppress adrenocorticotropic hormone dependent adrenal androgen synthesis	Weight gain Osteoporosis Adrenal suppression	–
Insulin-sensitising agents	Metformin	500-1000 mg	Decrease hyperinsulinaemia by increasing insulin sensitivity Lower insulin levels result in an increase of SHBG, thereby reducing the levels of circulating free androgens	Gastrointestinal distress Increased risk of cardiovascular events Liver dysfunction Lactic acidosis	These are best choices for hirsutism along with insulin resistance It is not suggested to prescribe these drugs just for hirsutism
	Rosiglitazone	4-8 mg
	Pioglitazone	10-30 mg

References

↑ Sachdeva S (2010). “Hirsutism: evaluation and treatment”. Indian J Dermatol. 55 (1): 3–7. doi:10.4103/0019-5154.60342. PMC 2856356. PMID 20418968.
↑ Murphy A, Cropp CS, Smith BS, Burkman RT, Zacur HA (1990). “Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women”. Fertil. Steril. 53 (1): 35–9. PMID 2136834.
↑ Givens, James R.; Andersen, Richard N.; Wiser, Winfred L.; Fish, Stewart A. (1974). “Dynamics of Suppression and Recovery of Plasma FSH, LH, Androstenedione and Testosterone in Polycystic Ovarian Disease Using an Oral Contraceptive”. The Journal of Clinical Endocrinology & Metabolism. 38 (5): 727–735. doi:10.1210/jcem-38-5-727. ISSN 0021-972X.
↑ Dewis P, Petsos P, Newman M, Anderson DC (1985). “The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol”. Clin. Endocrinol. (Oxf). 22 (1): 29–36. PMID 3156694.
↑ Shaw JC (1991). “Spironolactone in dermatologic therapy”. J. Am. Acad. Dermatol. 24 (2 Pt 1): 236–43. PMID 1826112.
↑ Lumachi F, Rondinone R (2003). “Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism”. Fertil. Steril. 79 (4): 942–6. PMID 12749435.
↑ Van der Spuy ZM, le Roux PA (2003). “Cyproterone acetate for hirsutism”. Cochrane Database Syst Rev (4): CD001125. doi:10.1002/14651858.CD001125. PMID 14583927.
↑ Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F (1998). “Effect of finasteride in idiopathic hirsutism”. J. Endocrinol. Invest. 21 (10): 694–8. doi:10.1007/BF03350800. PMID 9854686.
↑ Castelo-Branco C, Cancelo MJ (2010). “Comprehensive clinical management of hirsutism”. Gynecol. Endocrinol. 26 (7): 484–93. doi:10.3109/09513591003686353. PMID 20218823.
↑ Paparodis R, Dunaif A (2011). “The Hirsute woman: challenges in evaluation and management”. Endocr Pract. 17 (5): 807–18. doi:10.4158/EP11117.RA. PMID 21856600.
↑ Blume-Peytavi U (2013). “How to diagnose and treat medically women with excessive hair”. Dermatol Clin. 31 (1): 57–65. doi:10.1016/j.det.2012.08.009. PMID 23159176.
↑ Bode D, Seehusen DA, Baird D (2012). “Hirsutism in women”. Am Fam Physician. 85 (4): 373–80. PMID 22335316.
↑ Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ (2012). “Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society”. Hum. Reprod. Update. 18 (2): 146–70. doi:10.1093/humupd/dmr042. PMID 22064667.
↑ Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA (2008). “Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline”. J. Clin. Endocrinol. Metab. 93 (4): 1105–20. doi:10.1210/jc.2007-2437. PMID 18252793.
↑ Farshi S, Mansouri P, Rafie F (2012). “A randomized double blind, vehicle controlled bilateral comparison study of the efficacy and safety of finasteride 0.5% solution in combination with intense pulsed light in the treatment of facial hirsutism”. J Cosmet Laser Ther. 14 (4): 193–9. doi:10.3109/14764172.2012.699680. PMID 22658123.

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[pmid20418968-1] Sachdeva S (2010). “Hirsutism: evaluation and treatment”. Indian J Dermatol. 55 (1): 3–7. doi:10.4103/0019-5154.60342. PMC 2856356. PMID 20418968.

[pmid2136834-2] Murphy A, Cropp CS, Smith BS, Burkman RT, Zacur HA (1990). “Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women”. Fertil. Steril. 53 (1): 35–9. PMID 2136834.

[GivensAndersen1974-3] Givens, James R.; Andersen, Richard N.; Wiser, Winfred L.; Fish, Stewart A. (1974). “Dynamics of Suppression and Recovery of Plasma FSH, LH, Androstenedione and Testosterone in Polycystic Ovarian Disease Using an Oral Contraceptive”. The Journal of Clinical Endocrinology & Metabolism. 38 (5): 727–735. doi:10.1210/jcem-38-5-727. ISSN 0021-972X.

[pmid3156694-4] Dewis P, Petsos P, Newman M, Anderson DC (1985). “The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol”. Clin. Endocrinol. (Oxf). 22 (1): 29–36. PMID 3156694.

[pmid1826112-5] Shaw JC (1991). “Spironolactone in dermatologic therapy”. J. Am. Acad. Dermatol. 24 (2 Pt 1): 236–43. PMID 1826112.

[pmid12749435-6] Lumachi F, Rondinone R (2003). “Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism”. Fertil. Steril. 79 (4): 942–6. PMID 12749435.

[pmid14583927-7] Van der Spuy ZM, le Roux PA (2003). “Cyproterone acetate for hirsutism”. Cochrane Database Syst Rev (4): CD001125. doi:10.1002/14651858.CD001125. PMID 14583927.

[pmid9854686-8] Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F (1998). “Effect of finasteride in idiopathic hirsutism”. J. Endocrinol. Invest. 21 (10): 694–8. doi:10.1007/BF03350800. PMID 9854686.

[pmid20218823-9] Castelo-Branco C, Cancelo MJ (2010). “Comprehensive clinical management of hirsutism”. Gynecol. Endocrinol. 26 (7): 484–93. doi:10.3109/09513591003686353. PMID 20218823.

[pmid21856600-10] Paparodis R, Dunaif A (2011). “The Hirsute woman: challenges in evaluation and management”. Endocr Pract. 17 (5): 807–18. doi:10.4158/EP11117.RA. PMID 21856600.

[pmid23159176-11] Blume-Peytavi U (2013). “How to diagnose and treat medically women with excessive hair”. Dermatol Clin. 31 (1): 57–65. doi:10.1016/j.det.2012.08.009. PMID 23159176.

[pmid22335316-12] Bode D, Seehusen DA, Baird D (2012). “Hirsutism in women”. Am Fam Physician. 85 (4): 373–80. PMID 22335316.

[pmid22064667-13] Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ (2012). “Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society”. Hum. Reprod. Update. 18 (2): 146–70. doi:10.1093/humupd/dmr042. PMID 22064667.

[pmid18252793-14] Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA (2008). “Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline”. J. Clin. Endocrinol. Metab. 93 (4): 1105–20. doi:10.1210/jc.2007-2437. PMID 18252793.

[pmid22658123-15] Farshi S, Mansouri P, Rafie F (2012). “A randomized double blind, vehicle controlled bilateral comparison study of the efficacy and safety of finasteride 0.5% solution in combination with intense pulsed light in the treatment of facial hirsutism”. J Cosmet Laser Ther. 14 (4): 193–9. doi:10.3109/14764172.2012.699680. PMID 22658123.

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