Hirsutism affects a significant proportion of women of reproductive age. The incidence of hirsutism is highly variable depending on location and ethnicity, being higher in those of African or Mediterranean origin. It affects self-confidence, image and the quality of life of the woman.
Hirsutism is defined when there is an excessive amount of terminal hair growth in androgen-sensitive areas in women. Excessive hair growth occurs as a result of increased androgen production, increased skin sensitivity to androgens, or both. It must be differentiated from nonsexual pattern of excessive hair growth (hypertrichosis), which can be generalised and is independent of androgens.
Growth cycle of hair:
There are three phases of hair growth:
- 1.
anagen : the active cellular mitosis phase occurs in the basal matrix of the follicle and leads to rapid hair growth and this is the target stage of pharmacological agents used to treat hirsutism ;
- 2.
catagen : the involuting or regressing phase; and
- 3.
telogen : the resting or quiescent phase.
There are three types of hair:
- 1.
Lanugo : soft, nonpigmented hair;
- 2.
Vellus : short, fine, light-coloured hair, barely noticeable but covers most parts of the body;
- 3.
Terminal : thicker, longer, pigmented hair, can be found on the scalp, axillae, the genital region, eye brows, and eye lashes;
- 4.
The morphological basis of hirsutism is the excess transformation of vellus to terminal hair in a male pattern distribution.
Terminal hair is androgen dependent and their life cycle is influenced by the genetic and racial factors as well.
Facial hair has a longer growth phase, therefore therapy effect is seen after about 6–9 months of treatment.
The role of androgens:
- 1.
The androgens stimulate the conversion of vellus into terminal hair and prolong the anagen phase.
- 2.
Testosterone is the most important circulating androgen secreted from the ovaries and adrenal glands.
- 3.
Androgens are also produced through peripheral conversion of androgen precursors which is more marked in overweight/obese women.
- 4.
Free testosterone is the main bioactive portion as most circulating testosterone is bound by serum albumin and sex hormone-binding globulin (SHBG) which has a high affinity for testosterone and can modulate the bioavailability of free testosterone.
- 5.
Dihydrotestosterone (DHT) is more potent and is generated from testosterone by 5α reductase in the hair follicle and stimulates the dermal papilla to produce terminal hair instead of vellus hair.
- 6.
Hair follicles on the face, chest, lower abdomen, lower back and upper thighs are particularly androgen-sensitive; pubic and axillary hair is less so.
- 7.
Increased androgen levels transform vellus follicles in sex specific areas resulting in an increase in follicle size, diameter and the amount of time in the anagen phase.
Causes of hirsutism:
- 1.
Polycystic ovary syndrome (PCOS) : this is the most common cause of hirsutism, accounting for 70% to 80% of cases of hirsutism.
- 2.
Idiopathic hyperandrogenism : this accounts for 6%–15% of the causes of hirsutism. These women have elevated androgen levels, normal menses and normal ovaries at ultrasound.
- 3.
Idiopathic hirsutism : this is often due to an ethnic or familial trait and accounts for 4%–7% of cases of hirsutism. These individuals have regular menses and normal circulating androgen levels. An increased 5α reductase activity in the hair follicle or alteration in androgen receptor function may be the underlying cause.
- 4.
Late onset congenital adrenal hyperplasia (CAH) : this is an uncommon cause of androgen excess in 2%–4% of cases.
- 5.
Androgen-secreting ovarian and adrenal tumours are rare causes of hirsutism (0.2%).
Ovarian tumours include: granulosa cell tumours, Leydig cell tumours, Sertoli leydig cell tumours, luteomas of pregnancy and thecoma.
- 6.
Other endocrine causes include Cushing’s syndrome, acromegaly, thyroid dysfunction, and hyperprolactinaemia.
- 7.
Drugs : anabolic steroids, testosterone therapy, some oral contraceptives, danazol, cyclosporine, sodium valproate, phenytoin, streptomycin, diazoxide and minoxidil can lead to hirsutism.
- 8.
Obesity through increased peripheral conversion of androgen precursors which is more marked in overweight/obese women.
- 9.
Genetic cause : XY female.
- 10.
Menopausal women:
- a.
Relatively stable levels of testosterone production from ovaries can lead to an increase in hair growth.
- b.
Very little is known about acne and alopecia in these women.
- c.
Postmenopausal women with PCOS have higher 17-hydroxyprogesterone, androstenedione, DHEAS, total testosterone and FAI than women without PCOS.
- d.
In some women, raised levels of luteinising hormone (LH) can lead to stromal hyperplasia, high testosterone levels and severe hirsutism.
- a.
3.1
Clinical features and symptoms
Women with hirsutism may consult general practitioners, gynecologists, endocrinologists and dermatologists. A multidisciplinary approach might be necessary. Clinicians must undertake a focused history to differentiate hirsutism from virilism. Table 3.1 describes Rotterdam criteria for making the diagnosis of hirsutism.
- 1.
Hirsutism adversely impacts quality of life and most women readily treat hirsutism complicating assessment, hence health professionals should be prepared to assess any woman who complains of excess hair,
- 2.
Acne is associated with biochemical hyperandrogenism, yet the predictive value of acne alone is unclear and there is no accepted assessment tool.
- 3.
Most studies of women with alopecia reveal a relatively low prevalence of hyperandrogenemia and the predictive value of alopecia alone remains unclear, in part as there are many causes that can contribute to alopecia aside from hyperandrogenism. The signs and symptoms could be nonspecific or specific to the pathological causes ( Table 3.2 ).
Table 3.2
Focused history taking for women presenting with hirsutism.
Focused History
Data collected
History elicited
Age of onset (gradual or rapid), sites, current management, racial background, family history of (hirsutism, PCOS, androgenetic alopecia, type II diabetes, cardiovascular disease, late onset CAH, male-pattern balding before 30 years of age)
Other known current medical conditions and treatments
Menstrual history
History of menarche and menstrual symptoms(oligomenorrhea/amenorrhea), galactorrhea
History of Acne, androgenetic alopecia, seborrhoea
History of treatment with medications
Oral contraceptives with androgenic progestins (norgestrel, levonorgestrel, norethindrone)
Anabolic steroids, danazol, glucocorticoids, androgen therapy (testosterone)
Valproic acid
PCOS and HAIR-AN (hyperandrogenism, insulin resistance, and Acanthosis nigricans)
Weight gain, Acanthosis nigricans
Polydipsia/polyuria related to glucose intolerance
History of hypertension or hyperlipidaemia
Late-onset CAH
Onset prepuberty, premature pubarche, menstrual irregularities, primary amenorrhea
Hyperprolactinemia
History of galactorrhoea (spontaneous or expressible)
Pituitary tumor
Visual disturbance, headache
Adrenal or ovarian tumour
Virilisation (increased libido, clitoromegaly, voice—male like)
Thyroid dysfunction
Hot or cold intolerance, tremors, menstrual irregularities, diffuse scalp hair loss
| This criteria requires two out of three of the following to diagnose PCOS: |
| 1. Polycystic ovaries [either 12 or more follicles of 2–9 mm size or increased ovarian volume (>10 cm 3 )]. |
| 2. Oligo-ovulation or anovulation. |
| 3. Clinical and/or biochemical signs of hyperandrogenism. |
3.2
Examination
Mapping for the excessive terminal hair in androgen-dependent areas, including the face, chest, linea alba, lower back, buttocks, and anterior thighs by using Ferriman–Gallwey score to assess the degree of hirsutism.
It is important to differentiate between terminal hair and vellus hair, as vellus hair does not indicate hirsutism.
Examination of these patients should also include:
- 1.
measurement of body mass index (BMI);
- 2.
examination for acne, seborrhoea, presence or absence of virilisation;
- 3.
abdominal and pelvic masses;
- 4.
features found in endocrine disorders such as Cushing’s syndrome (full moon face and buffalo hump), galactorrhoea, thyroid enlargement, and hair loss;
- 5.
changes in quality of life; and
- 6.
assessment for symptoms of depression.
Ferriman–Gallwey scoring system (FG):
- 1.
In the original paper (1961), 11 body sites were recommended for assessment:
- a.
(Upper lip, chin, chest, upper and lower back, upper and lower abdomen, upper arm, forearm, thigh, and lower leg).
- a.
- 2.
And each site is scored on a 4-point scale (0=“no hair” to 4=“frankly virile”).
- 3.
The modified FG score excludes the forearm and lower leg as these areas are less or not sensitive to androgens.
- a.
A score of less than 8 is regarded as normal;
- b.
8 to 15 indicates mild hirsutism;
- c.
16 to 25 moderate hirsutism; and
- d.
> 25 indicates severe hirsutism.
- e.
Approximately 5%–10% of women of reproductive age are hirsute as assessed by this scoring system.
- a.
Limitations of FG scoring:
- 1.
Subjective in nature with wide interobserver variation;
- 2.
does not include areas such as sideburns and buttocks; and
- 3.
does not consider racial and ethnic variation.
- 4.
Middle Eastern and South Asian women have higher cut-off scores for hirsutism than those of Eastern Asian origin.
- 5.
Acanthosis is more common in women of Southeast Asian background, reflecting increased insulin resistance.
Investigations:
NICE (2014) recommends the following:
- 1.
No investigations for women with mild hirsutism and no other signs of PCOS or other underlying conditions.
- 2.
Recommends checking early morning testosterone levels in women with moderate-to-severe hirsutism how have no other signs of PCOS or other underlying conditions.
- 3.
The reference ranges for different laboratories vary widely.
- 4.
Clinical decisions should be guided by the reference ranges of the local laboratory.
- 1.
Testosterone concentration:
- a.
There is poor correlation between Testosterone concentrations and the severity of hirsutism, because of individual variations in hair follicle response to free testosterone.
- b.
Oral contraceptives users will have a falsely lower testosterone level.
- c.
A testosterone concentration of >5 nmol/L may suggest an androgen producing tumour.
- d.
A testosterone level >7 nmol/L should be seen at endocrinology clinic for further assessment.
- a.
- 2.
Free androgen index (FAI): This reflects the active form of circulating testosterone:
- a.
FAI is calculated as: FAI=[total testosterone ÷SHBG] × 100.
- b.
Obese and PCOS patients may have an elevated FAI, even with normal testosterone concentrations.
- c.
High androgens and low SHBG have also been linked to increased risk of cardiovascular disease.
- a.
- 3.
17 hydroxyprogesterone (17-OH P4):
- a.
Assessed to screen for late onset CAH.
- b.
Raised levels require confirmation by using a Short Synacthen test.
- c.
Short Synacthen test involves baseline assessment of 17OHP4, followed by an intramuscular injection of 250 micrograms of Synacthen. The levels of 17OHP4 are rechecked an hour later.
- d.
A significant rise in 17OHP4 levels is diagnostic of CAH.
- a.
- 4.
Dehydroepiandrosterone sulfate (DHEAS):
- a.
Where an adrenal cause is suspected.
- 5.
Dexamethasone suppression test or 24 hour urinary free cortisol :
- a.
For suspected cases of Cushing’s syndrome.
- 6.
Computed tomography (CT)/magnetic resonance imaging (MRI):
- a.
Pelvic CT and MRI to exclude the possibility of ovarian or adrenal androgen-producing tumour when testosterone concentrations are >5 nmol/L.
- a.
- 7.
Selective venous sampling of ovarian and adrenal veins
- a.
In cases where androgen-secreting tumours are suspected but pelvic imaging is negative.
- a.
- 8.
Prolactin (PRL)/thyroid function test (TSH):
- a.
To rule out hyperprolactinaemia and hypothyroidism for those presenting with both amenorrhea and hirsutism.
- a.
- 9.
Pregnancy test:
- a.
Pregnancy should always be ruled out before initiating any treatment in women with absent or irregular menstruation.
- a.
- 10.
Clinical management:
- a.
Treatment should be guided by the degree of severity of hirsutism, the woman’s preferences, her reproductive status, the underlying cause and any potential adverse effects.
- b.
Management strategies should aim to improve the quality of life, reduce the free androgen level, block peripheral androgens and improve cosmetic appearance by the removal of existing hair.
- c.
For pregnant or lactating women, no safe pharmacological treatments are available.
- d.
Condition specific clinical features and investigations have been summarised in Table 3.3 .
- a.
