Are You Confident of the Diagnosis?
Hirsutism should be suspected when there is an excessive amount of terminal hair growth on a woman’s body. This hair growth occurs in androgen-sensitive sites, the most common of which are the chin sideburns, above the upper lip, and chest (Figure 1).
Characteristic findings on physical examination
The diagnosis is generally made clinically. A detailed history and physical examination often provide sufficient information to exclude pathologic causes of hirsutism. Factors that suggest idiopathic hirsutism include pubertal onset, gradual progression, positive family history and the absence of virilization or menstrual irregularities.
The Ferriman-Gallwey score is a qualitative tool for evaluating and quantifying hair growth in women utilizing a scoring system to evaluate different body parts with scores ranging from 0 (no body hair) to 4 (extensive hair growth). This scoring system has limitations because of the somewhat subjective nature of the assessments and the difficulty of evaluating women who have removed the hair for cosmetic reasons, and is uncommonly utilized outside of the research setting.
Expected results of diagnostic studies
In most cases laboratory studies are unremarkable, and the diagnosis is one of exclusion, so-called idiopathic hirsutism. But in a subset of women the hirsutism may be a marker of underlying pathology including an androgen-producing tumor of the ovary or adrenal glands, functional ovarian hyperandrogenism (FOH)—formerly called polycystic ovarian syndrome—or late-onset congenital adrenal hyperplasia (LOCAH).
Features that would be most concerning for an androgen-producing tumor include severe hirsutism (pattern of hair growth as seen in a male), onset outside the peripubertal period, sudden onset with rapid progression, and concomitant signs of virilization such as clitoromegaly, voice deepening, male pattern alopecia and a male patterned escutcheon.
The usual laboratory workup for underlying pathology includes free and total testosterone, sex hormone binding globulin, human chorionic gonadotropin (HCG) and dehydroepiandrosterone sulfate (DHEAS). Abnormalities in these screening tests would prompt further honed evaluations. For example, markedly elevated testosterone and DHEAS would be highly indicative of an adrenal tumor warranting diagnositic imaging to confim location. Referral to an endocrinologist or gynecologist is indicated at the point that imaging studies are warranted. 21-hydroxylase deficiency is the most common cause of LOCAH, and one can screen for this by checking the 17-hydroxyprogesterone level if the patient has an elevated DHEAS.
Who is at Risk for Developing this Disease?
Idiopathic hirsutism has a strong genetic predilection, seen most frequently in populations such as Caucasian women of Mediterranean ancestry. Both FOH and LOCAH also demonstrate a strong familial predisposition. Even in women who meet the diagnostic criteria for FOH or LOCAH, hirsutism may not necessarily be present because of the variability in hair follicle sensitivity among women.
What is the Cause of the Disease?
Androgens are significantly associated with hair growth modulation including the transformation of a vellus hair to a terminal hair resulting in hirsutism. The severity of hirsutism does not correlate with androgen level because the hair follicles’ sensitivity to androgen stimulus varies considerably within and among women.
Testosterone, derived from adrenal glands, ovaries, as well as the peripheral conversion of androgen precursors, is a critical circulating hormone impacting hair growth. The unbound (free) testosterone is the main bioactive portion of plasma testosterone. Testosterone is converted to dihydrotestosterone (DHT), an even more potent androgen affecting hair growth, within the hair follicle by 5-alpha reductase. DHT directly binds to androgen receptors, acts as a transcription factor, and promotes hair growth at androgen-sensitive sites.
An increase in 5-alpha-reductase activitiy has been demonstrated in women with a diagnosis of idiopathic hirsutism who have normal circulating androgen levels.
In some instances, obesity directly contributes to the hirsutism due to increased production of androgens and/or decreased sex-hormone-binding globulin; weight reduction can improve the condition.
Systemic Implications and Complications
Once a diagnosis of hirsutism is made, it is prudent to search for pathologic causes, many of which can be excluded by a detailed history and physical examination. Workup as noted previously should be performed before defaulting to a diagnosis of idiopathic hirsutism. Even in the case of idiopathic hirsutism when an underlying disease process is lacking, it is associated with decreased self-image, decreased quality of life, and impingement on feminine identity; as such, the psychosocial ramifications of hirsutism are quite significant.
Hirsutism arising from elevated androgens as a result of a tumor or functional endocrinologic disorder of the ovaries or adrenals have their own specific comorbidities that need to be taken into consideration. Sertoli-Leydig cell tumor of the ovary may cause hirsutism and elevated testosterone levels. Imaging of the ovary should be performed and followed by a biopsy. This is prompted by a marked elevation of total testosterone. A gynecology consult should be obtained. A biopsy is the only way to know if the tumor is benign or malignant.
There is no magic bullet for treating hirsutism. First and foremost, the underlying disease process driving the hirsutism should be treated to address any systemic comorbidites. In the case of FOH for example, suppressing the ovarian androgen production with anti-androgens and insulin-sensitizing agents to ameliorate the concomitant reproductive and cardiovascular risks will often improve the hirsutism. That said, the overall aim in treating hirsutism is to remove hair permanently, to slow or stop new terminal hair growth, and to improve quality of life by improving the aesthetic appearance.
Oral contraceptives (OCP; combination estrogen/drosperinone)
Spironolactone, 100mg daily. Can increase to 200mg daily as tolerated.
Cyproterone acetate, 2 mg (usually in combination with estrogen in oral contraceptive Diane
Flutamide, 250mg twice daily
Finasteride, 1mg daily
Eflornithine hydrochloride once daily
Physical epilation with wax, shaving, threading, tweezing, electrolysis, depilatory creams
Treatment options are generally divided into medical and physical modalities. The medical treatments are directed at decreasing the androgen availability to exert negative effects on the hair follicle. These include suppression of ovarian androgen production with oral contraceptives, androgen receptor blockade with spironolactone, flutamide, or cyproterone acetate, and inhibition of 5-alpha reductase activity with finasteride. These are often utilized in patients with FOH as well as idiopathic hirsutism; all are contraindicated in the young female desiring to conceive and must be used continuously to maintain any benefit.
In my practice I find many cases of subtle functional ovarian hyperandrogenism, in which case I work with the reproductive endocrinologist to put them on a cocktail of metformin, spironolactone, and OCP. Whenever possible, OCP should be given along with spironolactone to provide adequate contraception as well as minimize the dysfunctional uterine bleeding often observed with spironolactone alone. If the androgens are completely normal, I typically prescribe OCP (combination estrogen/drosperinone) and spironolactone 100mg. I encourage laser hair removal whenever feasible in an effort to limit drug exposure.
A topical agent, eflornithine hydrochloride, has been shown to slow hair growth and is the only drug that has been approved the the US Food and Drug Administration for the treatment of facial hirsutism. Physical epilating modalities include waxing, shaving, threading, tweezing, and depilatory creams, which have the advantage of immediate hair removal but rapid regrowth as well; electrolysis has more permanence, but more side-effects such as postinflammatory hyperpigmentation and small risk of scarring. Photoepilation is a rapidly evolving technology utilizing laser and nonlaser light sources to damage hair follicles; this technology is costly and requires multiple treatment sessions to achieve satisfactory results.
Optimal Therapeutic Approach for this Disease
The choice of treatment is governed by underlying cause, age, contraceptive needs, and coexistence of metabolic aberrations that must be addressed. It is often the hirsutism, because it is the visible effect of androgen excess, that is most alarming to the patient; however, it is the metabolic abnormalities that have the greatest long-term health implications necessitating specific intervention. Depending on the unique patient characteristics, the best outcome is often achieved using a multifactorial approach employing both pharmaceutical and mechanical options.
All treatments for hirsutism must be balanced against the side-effect profile. In the case of underlying pathology, treatment should be focused on managing the co-morbitities and the treatment may cure or effectively manage the hirsutism. But in general, mechanical means of controlling, removing or destroying unwanted hairs should be considered complementary to medical management. Photoepilation shows the greatest promise for long-term hair removal without systemic side-effects. Referral to reproductive endocrinology is indicated when laboratory abnormalities are present because of the the comorbidities seen in ovarian hyperandrogenism including increased risks of type 2 diabetes, metabolic syndrome, infertility, and endometrial cancer.
Unusual Clinical Scenarios to Consider in Patient Management
Patients with FOH are underdiagnosed when screening is limited to a total testosterone. These women often have subtle laboratory abnormalities demonstrating a normal total testosterone (usually high end of normal), but an elevated free testosterone and low sex-hormone-binding globulin. Erroneously diagnosing these women with idiopathic hirsutisim fails to address important risk factors arising from the frequently coexistent metabolic syndrome.
What is the Evidence?
Rosenfield, RL. “Clincial practice: Hirsutism”. N Engl J Med. vol. 353. 2005. pp. 2578-88. (An exhaustive review of hirsutism including pathogenesis, diagnostic strategies, treatment regimens, as well as useful clinical images for grading hirsutism.)
Blume-Peytavi, U, Hahn, S. “Medical treatment of hirsutism”. Dermatol Ther. vol. 21. 2008. pp. 329-39. (Detailed anti-androgen and 5-alpha reductase treatment regimens.)
Mason, H, Colao, A, Blume-Peytavi, U, Rice, S, Qureshi, A, Pellatt, L. “Polycystic ovary syndrome trilogy: A translational and clinical review”. Clin Endocrinol. vol. 69. 2008. pp. 831-44. (An in-depth review of PCOS including pathogenesis and varied clinical and laboratory features.)
Cosma, M, Swiglo, BA, Flynn, DN. “Clinical review: Insulin sensitizers for the treatment of hirsutism: A systematic review and meta-analyses of randomized controlled trials”. J Clin Endocrinol Metab. vol. 93. 2008. pp. 1135-42. (An excellent review of the use of insulin sensitizers and meta-analyses of trial data.)
Randall, VA. “Androgens and hair growth”. Dermatol Ther. vol. 21. 2008. pp. 314-28. (Thorough review of the role androgens play in hair growth.)
Azziz, R, Carmina, E, Sawaya, ME. “Idiopathic hirsutism”. Endocr Rev. vol. 21. 2000. pp. 347-62. (An exhaustive review of hirsutism including hair growth regulation, evolving definition of hirsutism, pathogenesis, and therapy.)
Ibrahimi, OA, Avram, MM, Hanke, CW, Kilmer, SL, Anderson, RR. “Laser hair removal”. Dermatol Ther. vol. 24. 2011. pp. 94-107. (Excellent, updated and comprehesive review of laser/light devices for hair removal including discussion of hair follicle anatomy and physiology and mechanism of action/efficacy of devices in various patient populations.)
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