Hirsutism

Last updated
Hirsutism
Specialty Dermatology, endocrinology
Treatment Birth control pills, antiandrogens, insulin sensitizers [1]
Hirsutism depicted in a female patient with PCOS and nonclassic congenital adrenal hyperplasia PMC4103002 ircmj-16-9410-g001.png
Hirsutism depicted in a female patient with PCOS and nonclassic congenital adrenal hyperplasia

Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin hirsutus meaning "hairy". [2] It usually refers to a male pattern of hair growth in a female that may be a sign of a more serious medical condition, [3] especially if it develops well after puberty. [4] Cultural stigma against hirsutism can cause much psychological distress and social difficulty. [5] Discrimination based on facial hirsutism often leads to the avoidance of social situations and to symptoms of anxiety and depression. [6]

Contents

Hirsutism is usually the result of an underlying endocrine imbalance, which may be adrenal, ovarian, or central. [7] It can be caused by increased levels of androgen hormones. The amount and location of the hair is measured by a Ferriman-Gallwey score. It is different from hypertrichosis, which is excessive hair growth anywhere on the body. [3]

Treatments may include certain birth control pills, antiandrogens, or insulin sensitizers. [1]

Hirsutism affects between 5 and 15% of women across all ethnic backgrounds. [8] Depending on the definition and the underlying data, approximately 40% of women have some degree of facial hair. [9] About 10 to 15% of cases of hirsutism are idiopathic with no known cause. [10]

Causes

The causes of hirsutism can be divided into endocrine imbalances and non-endocrine etiologies. It is important to begin by first determining the distribution of body hair growth. If hair growth follows a male distribution, it could indicate the presence of increased androgens or hyperandrogenism. However, there are other hormones not related to androgens that can lead to hirsutism. A detailed history is taken by a provider in search of possible causes for hyperandrogenism or other non-endocrine-related causes. If the distribution of hair growth occurs throughout the body, this is referred to as hypertrichosis, not hirsutism. [11]

Endocrine causes

Endocrine causes of hirsutism include:

Non-endocrine causes

Causes of hirsutism not related to hyperandrogenism include:

Hormonal causes: [14] Description:Clinical cues:
Polycystic ovary syndrome PCOS is a condition characterized by excess androgens that can lead to hirsutism, irregular periods, and even infertility. The excess androgens can lead to disruptions in normal body hormones in the hypothalamic-pituitary-gonadal axis leading to these symptoms. [20] Characterized by having two of three Rotterdam criteria:
  • Oligomenorrhea (fewer than eight menses in a year)
  • Clinical or biochemical evidence of hyperandrogenism
  • Polycystic ovaries on ultrasound

[21]

Cushing's syndrome Cushing syndrome occurs when there is an endogenous or exogenous elevated levels of cortisol. One cause of endogenous Cushing syndrome is an adrenocorticotrophic hormone-secreting pituitary adenoma that is responsible for high secretion of not just cortisol but also androgens from the pituitary gland. [22] Cushing syndrome has an apparent symptoms including: Hirsutism weight gain, extra fat build up around the face, abdominal striae, and irregular menstruation. [22]
Congenital adrenal hyperplasia CAH can be attributed to several enzymatic deficiencies but the most common is 21-beta-hydroxylase. In CAH, a missing enzyme responsible for normal cortisol synthesis creates a build-up of androgen precursors. This precursor gets shunted to the androgen synthesis pathway leading to increased levels of androgen. Classical CAH is discovered at birth due to increased androgens during development causing ambitious genitalia. Meanwhile, non-classical CAH is found in puberty presenting as anovulation. [19] Can present similar to PCOS in non-classical CAH. Increase levels of 17-hydroxyprogesterone. [14] [19]
Androgen-secreting tumors Tumors in the adrenal glands or in the ovaries leading to increase levels of androgens. [19] Rapid progression and virilization symptoms. [14]
Other less common hormonal causes: Acromegaly: Elevated levels of insulin-like growth factor-1. [18] Hyperthyroidism or hypothyroidism: Elevated or decreased levels of thyroid hormones. [18] Hyperprolactinemia: Elevated levels of prolactin. [18] Each of these have their own distinct presentation. [19]

Diagnosis

Hirsutism is a clinical diagnosis of excessive androgenic, terminal hair growth. [23] A complete physical evaluation should be done prior to initiating more extensive studies, the examiner should differentiate between widespread body hair increase and male pattern virilization. [15] One method of evaluating hirsutism is the Ferriman-Gallwey Score which gives a score based on the amount and location of hair growth. [24] The Ferriman-Gallwey Score has various cutoffs due to variable expressivity of hair growth based on ethnic background. [25] [26]

Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound, due to the high prevalence of polycystic ovary syndrome (PCOS), as well as 17α-hydroxyprogesterone (because of the possibility of finding non-classic 21-hydroxylase deficiency [27] ). People with hirsutism may present with an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level, however, additional imaging is required to discriminate between malignant and benign etiologies of adrenal hyperandrogenism. [28] Levels greater than 700 μg/dL are indicative of adrenal gland dysfunction, particularly congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, PCOS and idiopathic hirsutism make up 90% of cases. [15]

Treatment

Treatment of hirsutism is indicated when hair growth causes patient distress. The two main approaches to treatment are pharmacologic therapies targeting androgen production/action, and direct hair removal methods including electrolysis and photo-epilation. These may be used independently or in combination. [29]

Pharmacologic therapies

Common medications consist of antiandrogens, insulin sensitizers, and oral contraceptive pills. All three types of therapy have demonstrated efficacy on their own, however insulin sensitizers are shown to be less effective than antiandrogens and oral contraceptive pills. [30] The therapies may be combined, as directed by a physician, in line with the patient's medical goals. Antiandrogens are drugs that block the effects of androgens like testosterone and dihydrotestosterone (DHT) in the body. [13] They are the most effective pharmacologic treatment for patient-important hirsutism, however they have teratogenic potential, and are therefore not recommended in people who are pregnant or desire pregnancy. Current data does not favor any one type of oral contraceptive over another. [30]

List of medications:

Other methods

See also

Related Research Articles

<span class="mw-page-title-main">Polycystic ovary syndrome</span> Set of symptoms caused by abnormal hormones in females

Polycystic ovary syndrome, or polycystic ovarian syndrome (PCOS), is the most common endocrine disorder in women of reproductive age. The syndrome is named after cysts which form on the ovaries of some people with this condition, though this is not a universal symptom, and not the underlying cause of the disorder.

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Ferriman–Gallwey score</span>

The Ferriman–Gallwey score is a method of evaluating and quantifying hirsutism in women. The method was originally published in 1961 by D. Ferriman and J.D. Gallwey in the Journal of Clinical Endocrinology.

Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.

<span class="mw-page-title-main">Spironolactone</span> Steroidal antiandrogen and antimineralocorticoid

Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure, low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women, and as a part of feminizing hormone therapy in trans women. Spironolactone is taken by mouth.

Adrenarche is an early stage in sexual maturation that happens in some higher primates and in humans, typically peaks at around 20 years of age, and is involved in the development of pubic hair, body odor, skin oiliness, axillary hair, sexual attraction/sexual desire/increased libido and mild acne. During adrenarche the adrenal glands secrete increased levels of weak adrenal androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A4), but without increased cortisol levels. Adrenarche is the result of the development of a new zone of the adrenal cortex, the zona reticularis. Adrenarche is a process related to puberty, but distinct from hypothalamic–pituitary–gonadal axis maturation and function.

Pubarche refers to the first appearance of pubic hair at puberty and it also marks the beginning of puberty. It is one of the physical changes of puberty and can occur independently of complete puberty. The early stage of sexual maturation, also known as adrenarche, is marked by characteristics including the development of pubic hair, axillary hair, adult apocrine body odor, acne, and increased oiliness of hair and skin. The Encyclopedia of Child and Adolescent Health corresponds SMR2 with pubarche, defining it as the development of pubic hair that occurs at a mean age of 11.6 years in females and 12.6 years in males. It further describes that pubarche's physical manifestation is vellus hair over the labia or the base of the penis. See Table 1 for the entirety of the sexual maturity rating description.

<span class="mw-page-title-main">Hyperandrogenism</span> Medical condition

Hyperandrogenism is a medical condition characterized by high levels of androgens. It is more common in women than men. Symptoms of hyperandrogenism may include acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation. Complications may include high blood cholesterol and diabetes. It occurs in approximately 5% of women of reproductive age.

<span class="mw-page-title-main">Flutamide</span> Chemical compound

Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women. It is taken by mouth, usually three times per day.

<span class="mw-page-title-main">Pattern hair loss</span> Medical condition

Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front hairline, loss of hair on the crown (vertex) of the scalp, or a combination of both. Female-pattern hair loss (FPHL) typically presents as a diffuse thinning of the hair across the entire scalp.

An androgen-dependent condition, disease, disorder, or syndrome, is a medical condition that is, in part or full, dependent on, or is sensitive to, the presence of androgenic activity in the body.

<span class="mw-page-title-main">Aromatase deficiency</span> Medical condition

Aromatase deficiency is a rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CYP19 (P450arom) which can lead to ambiguous genitalia and delayed puberty in females, continued linear growth into adulthood and osteoporosis in males and virilization in pregnant mothers. As of 2020, fewer than 15 cases have been identified in genetically male individuals and at least 30 cases in genetically female individuals.

Hyperthecosis, or ovarian hyperthecosis, is hyperplasia of the theca interna of the ovary. Hyperthecosis occurs when an area of luteinization occurs along with stromal hyperplasia. The luteinized cells produce androgens, which may lead to hirsutism and virilization in affected women.

<span class="mw-page-title-main">Prepubertal hypertrichosis</span> Medical condition

Prepubertal hypertrichosis, also known as childhood hypertrichosis, is a cutaneous condition characterized by increased hair growth, found in otherwise healthy infants and children. Prepubertal hypertrichosis is a cosmetic condition and does not affect any other health aspect. Individuals with this condition may suffer with low self esteem and mental health issues due to societal perceptions of what a "normal" appearance should be. The mechanism of prepubertal hypertrichosis is unclear, but causes may include genetics, systemic illnesses, or medications.

<span class="mw-page-title-main">Cyproterone acetate</span> Chemical compound

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender women, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

<span class="mw-page-title-main">Benorterone</span> Chemical compound

Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.

<span class="mw-page-title-main">Nonsteroidal antiandrogen</span> Antiandrogen with a nonsteroidal chemical structure

A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.

<span class="mw-page-title-main">HAIR-AN syndrome</span> Medical condition

The HAIR-AN syndrome is a rare subtype of polycystic ovary syndrome (PCOS) characterized by hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The symptoms of the HAIR-AN syndrome are largely due to severe insulin resistance, which can be secondary to blocking antibodies against the insulin receptor or genetically absent/reduced insulin receptor number/function. Insulin resistance leads to hyperinsulinemia which, in turn, leads to an excess production of androgen hormones by the ovaries. High levels of androgen hormones (hyperandrogenism) in females causes excessive hair growth, acne and irregular menstruation. Patients with both underlying mechanisms of insulin resistance may have more severe hyperandrogenism. Insulin resistance is also associated with diabetes, heart disease and excessive darkening of the skin

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.

<span class="mw-page-title-main">Ethinylestradiol/cyproterone acetate</span> Combination drug

Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and antiandrogen, which is used as a birth control pill to prevent pregnancy in women. It is also used to treat androgen-dependent conditions in women such as acne, seborrhea, excessive facial/body hair growth, scalp hair loss, and high androgen levels associated with ovaries with cysts. The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.

References

  1. 1 2 3 Barrionuevo, P; Nabhan, M; Altayar, O; Wang, Z; Erwin, PJ; Asi, N; Martin, KA; Murad, MH (1 April 2018). "Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis". The Journal of Clinical Endocrinology and Metabolism. 103 (4): 1258–1264. doi: 10.1210/jc.2017-02052 . PMID   29522176.
  2. "hirsute adjective - Definition, pictures, pronunciation and usage notes | Oxford Advanced Learner's Dictionary". www.oxfordlearnersdictionaries.com. Retrieved 2021-07-22.
  3. 1 2 "Merck Manuals online medical Library". Merck & Co. Retrieved 2011-03-04.
  4. Sachdeva S (2010). "Hirsutism: Evaluation and Treatment". Indian J Dermatol. 55 (1): 3–7. doi: 10.4103/0019-5154.60342 . PMC   2856356 . PMID   20418968.
  5. Barth JH, Catalan J, Cherry CA, Day A (September 1993). "Psychological morbidity in women referred for treatment of hirsutism". J Psychosom Res. 37 (6): 615–9. doi:10.1016/0022-3999(93)90056-L. PMID   8410747.
  6. Jackson J, Caro JJ; Caro G, Garfield F; Huber F, Zhou W; Lin CS, Shander D & Schrode K (2007). the Eflornithine HCl Study Group. "The effect of eflornithine 13.9% cream on the bother and discomfort due to hirsutism". International Journal of Dermatology. 46 (9): 976–981. doi:10.1111/j.1365-4632.2007.03270.x. PMID   17822506. S2CID   25986442.
  7. Blume-Peytavi U, Hahn S. "Medical treatment of hirsutism. Dermatol Ther. 2008 Sep-Oct; 21(5): 329-39. Review".{{cite journal}}: Cite journal requires |journal= (help)
  8. Azziz R. (May 2003). "The evaluation and management of hirsutism". Obstet Gynecol. 101 (5 pt 1): 995–1007. doi:10.1016/s0029-7844(02)02725-4. PMID   12738163.
  9. Blume-Peytavi U, Gieler U, Hoffmann R, Shapiro J (2007). "Unwanted Facial Hair: Affects, Effects and Solutions". Dermatology (Basel). 215 (2): 139–146. doi:10.1159/000104266. PMID   17684377. S2CID   9589835.
  10. 1 2 3 4 de Kroon RW, den Heijer M, Heijboer AC (June 2022). "Is idiopathic hirsutism idiopathic?". Clin Chim Acta. 531: 17–24. doi: 10.1016/j.cca.2022.03.011 . PMID   35292252. S2CID   247419684.
  11. Sachdeva, Silonie (2010). "Hirsutism: Evaluation and treatment". Indian Journal of Dermatology. 55 (1): 3–7. doi: 10.4103/0019-5154.60342 . ISSN   0019-5154. PMC   2856356 . PMID   20418968.
  12. Somani N, Harrison S, Bergfeld WF (2008). "The clinical evaluation of hirsutism". Dermatol Ther. 21 (5): 376–91. doi:10.1111/j.1529-8019.2008.00219.x. PMID   18844715. S2CID   34029116.
  13. 1 2 3 4 Unluhizarci K, Kaltsas G, Kelestimur F (2012). "Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism". Eur J Clin Invest. 42 (1): 86–94. doi:10.1111/j.1365-2362.2011.02550.x. PMID   21623779. S2CID   23701817.
  14. 1 2 3 4 5 6 Radi, Suhaib; Tamilia, Michael (2019-12-30). "Adrenocortical carcinoma: an ominous cause of hirsutism". BMJ Case Reports. 12 (12): e232547. doi:10.1136/bcr-2019-232547. ISSN   1757-790X. PMC   6954802 . PMID   31892624.
  15. 1 2 3 4 5 6 Sachdeva, Silonie (2010). "Hirsutism: Evaluation and treatment". Indian Journal of Dermatology. 55 (1): 3–7. doi: 10.4103/0019-5154.60342 . PMC   2856356 . PMID   20418968.
  16. Chellini PR, Pirmez R, Raso P, Sodré CT (2015). "Generalized Hypertrichosis Induced by Topical Minoxidil in an Adult Woman". Int J Trichology. 7 (4): 182–3. doi: 10.4103/0974-7753.171587 . PMC   4738488 . PMID   26903750.
  17. Dawber RP, Rundegren J (2003). "Hypertrichosis in females applying minoxidil topical solution and in normal controls". J Eur Acad Dermatol Venereol. 17 (3): 271–5. doi:10.1046/j.1468-3083.2003.00621.x. PMID   12702063. S2CID   23329383.
  18. 1 2 3 4 Hafsi, Wissem; Badri, Talel (2022), "Hirsutism", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   29262139 , retrieved 2022-09-15
  19. 1 2 3 4 5 Bode, David; Seehusen, Dean A.; Baird, Drew (2012-02-15). "Hirsutism in Women". American Family Physician. 85 (4): 373–380. PMID   22335316.
  20. Witchel SF, Oberfield SE, Peña AS (August 2019). "Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls". J Endocr Soc. 3 (8): 1545–1573. doi:10.1210/js.2019-00078. PMC   6676075 . PMID   31384717.
  21. Legro, Richard S.; Arslanian, Silva A.; Ehrmann, David A.; Hoeger, Kathleen M.; Murad, M. Hassan; Pasquali, Renato; Welt, Corrine K. (December 2013). "Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 98 (12): 4565–4592. doi:10.1210/jc.2013-2350. ISSN   0021-972X. PMC   5399492 . PMID   24151290.
  22. 1 2 Mihailidis, John; Dermesropian, Racha; Taxel, Pamela; Luthra, Pooja; Grant-Kels, Jane M. (2015-06-04). "Endocrine evaluation of hirsutism". International Journal of Women's Dermatology. 1 (2): 90–94. doi:10.1016/j.ijwd.2015.04.003. ISSN   2352-6475. PMC   5418744 . PMID   28491965.
  23. Ferriman, D.; Gallwey, J. D. (November 1961). "Clinical assessment of body hair growth in women". The Journal of Clinical Endocrinology and Metabolism. 21 (11): 1440–1447. doi:10.1210/jcem-21-11-1440. ISSN   0021-972X. PMID   13892577.
  24. Ferriman D, Gallwey JD (November 1961). "Clinical assessment of body hair growth in women". J. Clin. Endocrinol. Metab. 21 (11): 1440–7. doi:10.1210/jcem-21-11-1440. PMID   13892577.
  25. Cheewadhanaraks, Sopon; Peeyananjarassri, Krantarat; Choksuchat, Chainarong (May 2004). "Clinical diagnosis of hirsutism in Thai women". Journal of the Medical Association of Thailand = Chotmaihet Thangphaet. 87 (5): 459–463. ISSN   0125-2208. PMID   15222512.
  26. Escobar-Morreale, H. F.; Carmina, E.; Dewailly, D.; Gambineri, A.; Kelestimur, F.; Moghetti, P.; Pugeat, M.; Qiao, J.; Wijeyaratne, C. N.; Witchel, S. F.; Norman, R. J. (March 2012). "Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society". Human Reproduction Update. 18 (2): 146–170. doi: 10.1093/humupd/dmr042 . ISSN   1460-2369. PMID   22064667.
  27. Di Fede G, Mansueto P, Pepe I, Rini GB, Carmina E (2010). "High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms" (PDF). Fertil. Steril. 94 (1): 194–7. doi:10.1016/j.fertnstert.2009.02.056. hdl: 10447/36367 . PMID   19338993.
  28. d'Alva, Catarina B.; Abiven-Lepage, Gwenaelle; Viallon, Vivian; Groussin, Lionel; Dugue, Marie Annick; Bertagna, Xavier; Bertherat, Jerôme (2008-11-01). "Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess". European Journal of Endocrinology. 159 (5): 641–647. doi:10.1530/EJE-08-0324. ISSN   0804-4643. PMID   18708437. S2CID   6342456.
  29. Martin, Kathryn A; Anderson, R Rox; Chang, R Jeffrey; Ehrmann, David A; Lobo, Rogerio A; Murad, M Hassan; Pugeat, Michel M; Rosenfield, Robert L (2018-03-07). "Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society* Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 103 (4): 1233–1257. doi: 10.1210/jc.2018-00241 . ISSN   0021-972X. PMID   29522147.
  30. 1 2 Barrionuevo, Patricia; Nabhan, Mohammed; Altayar, Osama; Wang, Zhen; Erwin, Patricia J; Asi, Noor; Martin, Kathryn A; Murad, M Hassan (2018-03-07). "Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis". The Journal of Clinical Endocrinology & Metabolism. 103 (4): 1258–1264. doi: 10.1210/jc.2017-02052 . ISSN   0021-972X. PMID   29522176. S2CID   3783739.
  31. 1 2 Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B (22 January 2009). Evidence-Based Dermatology. John Wiley & Sons. pp. 529–. ISBN   978-1-4443-0017-8.
  32. 1 2 Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clinica Belgica. 68 (4): 268–74. doi:10.2143/ACB.3267. PMID   24455796. S2CID   39120534.
  33. 1 2 Müderris II, Bayram F, Ozçelik B, Güven M (February 2002). "New alternative treatment in hirsutism: bicalutamide 25 mg/day". Gynecological Endocrinology. 16 (1): 63–6. doi:10.1080/gye.16.1.63.66. PMID   11915584. S2CID   6942048.
  34. 1 2 3 4 van Zuuren, Esther J; Fedorowicz, Zbys; Carter, Ben; Pandis, Nikolaos (2015-04-28). "Interventions for hirsutism (excluding laser and photoepilation therapy alone)". Cochrane Database of Systematic Reviews. 2015 (4): CD010334. doi:10.1002/14651858.CD010334.pub2. ISSN   1465-1858. PMC   6481758 . PMID   25918921.
  35. 1 2 Ekback, Maria Palmetun (2017). "Hirsutism, What to do?" (PDF). International Journal of Endocrinology and Metabolic Disorders. 3 (3). doi: 10.16966/2380-548X.140 . ISSN   2380-548X.
  36. 1 2 3 4 Ulrike Blume-Peytavi; David A. Whiting; Ralph M. Trüeb (26 June 2008). Hair Growth and Disorders. Springer Science & Business Media. pp. 181–, 369–. ISBN   978-3-540-46911-7.
  37. 1 2 3 4 5 Somani N, Turvy D (2014). "Hirsutism: an evidence-based treatment update". Am J Clin Dermatol. 15 (3): 247–66. doi:10.1007/s40257-014-0078-4. PMID   24889738. S2CID   45234892.
  38. Wolf, John E.; Shander, Douglas; Huber, Ferdinand; Jackson, Joseph; Lin, Chen-Sheng; Mathes, Barbara M.; Schrode, Kathy; the Eflornithine HCl Study Group (January 2007). "Randomized, double-blind clinical evaluation of the efficacy and safety of topical eflornithine HCl 13.9% cream in the treatment of women with facial hair: Eflornithine treatment for unwanted facial hair". International Journal of Dermatology. 46 (1): 94–98. doi:10.1111/j.1365-4632.2006.03079.x. PMID   17214730. S2CID   10795478.
  39. Bentham Science Publishers (September 1999). Current Pharmaceutical Design. Bentham Science Publishers. pp. 712–717.
  40. Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A (2017). "Flutamide-induced hepatotoxicity: ethical and scientific issues". Eur Rev Med Pharmacol Sci. 21 (1 Suppl): 69–77. PMID   28379593.
  41. Adam Ostrzenski (2002). Gynecology: Integrating Conventional, Complementary, and Natural Alternative Therapy. Lippincott Williams & Wilkins. pp. 86–. ISBN   978-0-7817-2761-7.
  42. Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1196, 1208. ISBN   978-0-7817-1750-2.
  43. Mongioi, A.; Maugeri, G.; Macchi, M.; Calogero, A.; Vicari, E.; Coniglione, F.; Aliffi, A.; Sipione, C.; D'Agata, R. (February 1986). "Effect of gonadotrophin-releasing hormone analogue (GnRH-A) administration on serum gonadotrophin and steroid levels in patients with polycystic ovarian disease". Acta Endocrinologica. 111 (2): 228–234. doi:10.1530/acta.0.1110228. ISSN   0001-5598. PMID   3082098.
  44. Karakurt F, Sahin I, Güler S, et al. (April 2008). "Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: a randomised controlled study". Adv Ther. 25 (4): 321–8. doi:10.1007/s12325-008-0039-5. PMID   18389188. S2CID   23641936.
  45. Taylor SI, Dons RF, Hernandez E, Roth J, Gorden P (December 1982). "Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor". Ann. Intern. Med. 97 (6): 851–5. doi:10.7326/0003-4819-97-6-851. PMID   7149493.