Hirsutism
Hirsutism - Summary
Hirsutism is the growth of excess terminal hair (dark, thick, and coarse hair) on the face, chest, linea alba (midline of the abdomen), lower back, buttocks, and anterior thighs in women.
Some hair growth in androgen dependent areas is normal, and there is no clear cut-off for defining excessive hair growth. It is important to differentiate between terminal hair and vellus hair which is soft, fine, and unpigmented. Vellus hair does not indicate hirsutism.
Excess hair growth occurs as a result of increased androgen production or increased skin sensitivity to androgens, or both.
In pre-menopausal women polycystic ovary syndrome (PCOS) is the most common cause of hirsutism (72%). No apparent underlying cause is found in about a quarter of women. Androgen secreting tumours, congenital adrenal hyperplasia, Cushing’s syndrome, acromegaly, and drugs are less common causes of hirsutism.
In post-menopausal women, a reduction in ovarian estradiol with relatively stable levels of testosterone production or increasing concentrations of luteinizing hormone are often the cause.
An underlying cause should be looked for.
In women with mild hirsutism and no other signs of PCOS or other underlying condition, investigations are not usually necessary.
In women with moderate-to-severe hirsutism and no other signs of PCOS or other underlying condition, plasma testosterone should be measured. If the testosterone level is greater than 5 nanomol/L, specialist advice should be obtained.
Management options in primary care for premenopausal women include:
Weight loss (if obese).
Cosmetic hair reduction and removal.
Co-cyprindiol (Dianette®) or a combined oral contraceptive (COC) containing drospirenone (for example Yasmin®).
Eflornithine cream (for facial hirsutism).
Management options in primary care for postmenopausal women include:
Cosmetic hair reduction and removal.
Eflornithine cream (for facial hirsutism).
Referral to a specialist is recommended if:
Hair growth is of recent onset and rapidly progressing, there are signs of virilization, hirsutism is particularly severe, or an abdominal or pelvic mass is detected.
Hair growth worsens despite treatment.
Treatment has not been effective after 6–12 months.
Treatments that may be offered by specialists include:
Anti-androgens (such as high-dose cyproterone acetate, spironolactone, and flutamide).
5-alpha-reductase inhibitors (such as finasteride).
Insulin-sensitizing drugs (such as metformin and pioglitazone).
Gonadotrophin-releasing hormone analogues (such as goserelin and leuprorelin).
Have I got the right topic?
This CKS topic covers the management of women with hirsutism in primary care.
This CKS topic does not cover excess hair growth in children or in men. It also does not cover, in any detail, the treatments for hirsutism that are used in secondary care.
There are separate CKS topics on Acne vulgaris, Menopause, and Polycystic ovary syndrome.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
CKS gratefully acknowledges the contribution of the British Association of Dermatologists in the development of this topic.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
June 2011 — minor update. Broken link fixed. Issued June 2011.
September 2009 to January 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 September 2009.
HTAs (Health Technology Assessments)
No new HTAs since 1 September 2009.
Economic appraisals
No new economic appraisals relevant to England since 1 September 2009.
Systematic reviews and meta-analyses
No new systematic review or meta-analysis since 1 September 2009.
Primary evidence
No new randomized controlled trials published in the major journals since 1 September 2009.
New policies
No new national policies or guidelines since 1 September 2009.
New safety alerts
No new safety alerts since 1 September 2009.
Changes in product availability
No changes in product availability since 1 September 2009.
Goals and outcome measures
Goals
To identify any underlying cause of hirsutism
To refer early (if indicated) for investigation of underlying cause
To appropriately treat the condition in primary care
To appropriately refer people to secondary care for specialist treatment
To provide appropriate advice regarding non-drug treatments
Background information
Definition
What is it?
Hirsutism is the growth of excess terminal hair in androgen-dependent areas (face, chest, linea alba, lower back, buttocks, and anterior thighs) in women [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
Excess hair growth occurs as a result of increased androgen production or increased skin sensitivity to androgens, or both [Sathyapalan and Atkin, 2009].
Causes
What causes it?
In premenopausal women:
Polycystic ovary syndrome is the most common cause of hirsutism (72%).
Idiopathic hirsutism (where there is no apparent underlying cause and serum androgen levels are normal) occurs in about 23% of women. In these women, hirsutism is thought to be due to increased skin sensitivity to androgens. This may, in part, be caused by increased alpha-reductase activity enhancing the local conversion of testosterone to the more potent dihydrotestosterone.
Less commonly, hirsutism may be caused by:
Non-classic (or late onset) congenital adrenal hyperplasia (4.3%).
Androgen-secreting tumour (ovarian or adrenal; 0.2%).
Classic congenital adrenal hyperplasia.
Cushing's syndrome.
Acromegaly.
Drugs (for example anabolic steroids, danazol, sodium valproate).
In menopausal women, a reduction in ovarian estradiol with relatively stable levels of testosterone production can lead to an increase in hair growth. In some women, increasing concentrations of luteinizing hormone lead to stromal hyperplasia, high testosterone levels, and severe hirsutism.
[Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009; Sathyapalan and Atkin, 2009]
Prevalence
How common is it?
The estimated prevalence of hirsutism is 5–15% in women of reproductive age [Kumar et al, 2009].
Prevalence rates vary considerably, according to the cut-off used for definition.
Complications
What are the complications?
Hirsutism can have a profound effect on psychological well being and quality of life; the impact can be similar to that of asthma, epilepsy, or diabetes [Koulouri and Conway, 2009].
In particular, facial hirsutism causes considerable emotional distress and social embarrassment [Lavery et al, 2005].
Rarely, hirsutism can be a sign of a life-threatening underlying condition.
Diagnosis
Diagnosis of hirsutism
Diagnosis
How do I know my patient has it?
Look for excessive terminal hair in androgen-dependent areas including the face, chest, linea alba, lower back, buttocks, and anterior thighs.
Some hair growth in androgen dependent areas is normal, and there is no clear cut-off for defining excessive hair growth.
It is important to differentiate between terminal hair (which is dark, thick, and coarse) and vellus hair (which is soft, fine, and unpigmented). Vellus hair does not indicate hirsutism.
Differential diagnosis
What else might it be?
Hypertrichosis is excessive hair growth distributed in a generalized, nonsexual pattern.
It may be hereditary or drug-induced.
It is not caused by excess androgen.
Assessment for an underlying cause
How should I assess for an underlying cause of hirsutism?
Ask about, and look for, features of polycystic ovary syndrome (PCOS) — oligomenorrhoea or amenorrhoea, infertility, acne, hair loss from the scalp, central obesity, acanthosis nigricans.
For information on the diagnosis of PCOS, see the section on Diagnosis in the CKS topic on Polycystic ovary syndrome.
Ask about, and look for, features of an androgen secreting tumour — sudden onset or rapid progression of hair growth, severe hirsutism, signs of virilization (hair loss from the scalp, voice deepening, increased muscle bulk, clitoromegaly), a pelvic or abdominal mass.
Urgently refer the woman if an androgen-secreting tumour is clinically suspected.
Ask about, and look for, features of Cushing's syndrome — for example: weight gain in the face (moon face), neck region, upper back, and torso; stretch marks; easy bruising; and proximal muscle weakness.
Refer the woman if Cushing's syndrome is suspected.
Consider checking free cortisol levels (using a 24-hour urine collection) or performing a dexamethasone suppression test before the outpatient appointment.
Ask about current medication, including any use of anabolic steroids.
In women with mild hirsutism and no other signs of PCOS or other underlying condition:
Investigations are not usually necessary.
In women with moderate-to-severe hirsutism and no other signs of PCOS or other underlying condition:
Measure plasma testosterone.
If the testosterone level is greater than 5 nanomol/L, seek specialist advice.
Consider screening for late-onset congenital adrenal hyperplasia in women who are at high risk (for example those with a positive family history, or from a high-risk ethnic group [such as Ashkenazi Jewish, Hispanic, and Slavic people]), especially if they wish to conceive.
Measurement of early morning 17-hydroxyprogesterone is recommended — check with the local laboratory for details of when and how this test should be performed.
Refer the woman to an endocrinologist if 17-hydroxyprogesterone levels are elevated.
Basis for recommendation
Basis for recommendation
Underlying conditions
The recommendations to ask about, and look for, features of polycystic ovary syndrome (PCOS), androgen-secreting tumours, and Cushing's syndrome are based on the fact that these are known underlying causes of hirsutism.
Medication
Certain drugs, including danazol, sodium valproate, and anabolic steroids can cause hirsutism [Martin et al, 2008].
Investigations for mild hirsutism with no other signs of PCOS or other underlying condition
The recommendation that investigations are not necessary in women with mild hirsutism and no other signs of PCOS or other underlying condition is in line with recommendations from an Endocrine Society clinical practice guideline, based on very low quality evidence [Martin et al, 2008]. This is supported by the opinion of CKS expert reviewers.
Checking testosterone levels in women with moderate-to-severe hirsutism and no other signs of PCOS or other underlying condition
The recommendation to check testosterone levels in women with moderate-to-severe hirsutism and no other signs of PCOS or other underlying condition is in line with recommendations from an Endocrine Society clinical practice guideline, based on very low quality evidence [Martin et al, 2008].
Screening for late-onset congenital adrenal hyperplasia
The recommendation to consider screening for late-onset congenital adrenal hyperplasia in women at high risk is based on a narrative text on rational testing [Sathyapalan and Atkin, 2009].
Around 1–10% of women with hyperandrogenaemia have late-onset congenital hyperplasia, which is clinically indistinguishable from PCOS.
The prevalence is higher in Hispanic, Ashkenazi Jewish, and Slavic people. Therefore, screening in this group seems sensible.
Identification of late-onset congenital adrenal hyperplasia in women who are trying to conceive is important so that glucocorticoid treatment can be initiated in the peri-conceptual period [Koulouri and Conway, 2009].
Management
Management
Scenario: Management: covers the management of women and girls with hirsutism.
Scenario: Management
Scenario: Management of hirsutism
Assessment of severity
How should I assess the severity of hirsutism?
Assess the severity of hair growth and the impact on the woman's quality of life, as this may guide treatment.
Some hair growth in the androgen-dependent areas is normal, and there is no clear cut-off for defining excessive hair growth.
A subjective approach is generally appropriate in primary care, using the woman's own perception of her condition and the extent it impacts on her quality of life.
Hirsutism can be more formally evaluated using the Ferriman–Gallwey scoring system; however, this scoring system has several limitations, and is impractical for routine use in clinical practice.
Ferriman-Gallwey scoring system
Ferriman-Gallwey scoring system
The Ferriman–Gallwey scoring system has been designed to assess the severity of hirsutism.
Each of the nine body areas most sensitive to androgen production is assigned a score from 0 (no hair) to 4 (heavy hair growth).
The nine areas are: upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, the upper arms, and the thighs.
The separate scores are added to provide a total score (0–36).
A score of more than 15 is considered to indicate moderate or severe hirsutism.
Basis for recommendation
Basis for recommendation
Assessment of severity
The recommendation to assess severity is based on expert opinion in guidelines and narrative reviews [Lavery et al, 2005; Martin et al, 2008; Kumar et al, 2009].
Definition of excessive hair growth
There is no clear cut-off for defining excessive hair growth. Although many clinical trials use a Ferriman–Gallwey score of eight or more to indicate hirsutism, many women with a lower score consider themselves hirsute.
In a prospective observational study in 633 women, a Ferriman–Gallwey score of two or less was observed in approximately 75% of women; 16% of these women considered themselves to be hirsute [DeUgarte et al, 2006].
Of the 25% of women with a Ferriman–Gallwey score of three or more, 70% considered themselves to be hirsute.
Similarly, 70% of women with a Ferriman–Gallwey score of eight or more considered themselves to be hirsute.
Overall there were no differences between black and white women.
The Ferriman–Gallwey scoring system is a validated tool. However, it has a number of limitations, and although it is valuable as a clinical research tool, it is generally not considered to be practical for use in primary care [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009; Kumar et al, 2009].
Management (premenopausal)
How should I manage hirsutism in premenopausal women?
For premenopausal women (with or without polycystic ovary syndrome):
Encourage weight loss in women who are overweight or obese (see the CKS topic on Obesity for more information).
Discuss cosmetic methods of hair reduction and removal, as these will remain an important part of management.
If hirsutism is mild and does not significantly impact on the woman's quality of life, consider no additional treatment.
If additional treatment is required, offer co-cyprindiol (Dianette®) or a combined oral contraceptive (COC) containing drospirenone (for example Yasmin®).
Co-cyprindiol (Dianette®; a combination of ethinylestradiol and the anti-androgen cyproterone acetate) is licensed for the treatment of moderately-severe hirsutism but should be stopped three or four menstrual cycles after the woman's hirsutism has completely resolved because of an increased risk of venous thromboembolism.
Yasmin® (a combination of ethinylestradiol and drospirenone) is not licensed specifically for hirsutism but is an alternative to co-cyprindiol for women who require long-term treatment. Yasmin® is more expensive than co-cyprindiol.
See the CKS topic on Contraception - combined hormonal methods for a full discussion of the risks of COCs.
Advise the woman that treatment may take at least 6 months to work.
If relapse occurs when co-cyprindiol is stopped, consider:
Intermittent use of co-cyprindiol — stopping treatment after resolution occurs, and starting again if symptoms reappear (licensed use).
Switching to a COC containing drospirenone (Yasmin®).
Some experts recommend continuing treatment with co-cyprindiol if the above measures fail.
If COCs are contraindicated or have not worked, offer women with facial hirsutism topical eflornithine.
Benefit should be noticed in 6–8 weeks, and eflornithine should be discontinued if no benefit is seen within 4 months of starting treatment.
If improvement is seen, continued treatment is necessary to maintain the benefits. Once the cream is discontinued, hair growth returns to pretreatment levels within about 8 weeks.
Eflornithine is contraindicated during pregnancy and breastfeeding.
Methods of hair removal
Methods of hair removal
Cosmetic treatment is not usually available on the NHS.
Cosmetic procedures can be applied in a domestic setting.
Shaving does not increase the rate of hair growth or thicken hair, contrary to popular belief. It is a useful technique and yields instant results. However, it does leave stubble that is unpleasant, unsightly, and sharp, and may irritate the skin.
Waxing and plucking are effective, but can be painful and may cause scarring, folliculitis, and hyperpigmentation. These techniques can also lead to resistance to electrolysis.
Bleaching can improve the appearance of dark hair in the short term, but may also lead to skin irritation.
Skin irritation is problematic as it is itchy, unsightly, and paradoxically can lead to increased hair growth.
Cosmetic procedures carried out in specialist clinics tend to have a longer effect, although they are not usually permanent.
Electrolysis uses a localized electric charge to destroy hair cells at the bulb. It is effective, but is time-consuming, painful, and may leave scars or pigmentation changes.
Lasers are used selectively in the process of photothermolysis, a more recent technique that generally yields better results than electrolysis. It only affects hair in the growing phase, so must be repeated over several months. Laser hair removal is most effective in women with pale skin and dark hair.
Basis for recommendation
Basis for recommendation
Weight loss
The recommendation on weight loss for women who are overweight or obese is based on expert opinion [Lavery et al, 2005].
Weight loss is likely to improve metabolic and endocrine parameters; however, in one study of overweight women with polycystic ovary syndrome, there was no direct effect of weight loss on hirsutism [Moran et al, 2003].
Permanent hair reduction techniques
There are very few published studies on electrolysis; however, electrolysis has been widely used for a number of years.
Limited evidence from a Cochrane systematic review (11 randomized controlled trials [RCTs]) suggests that some laser and photoepilation treatments may lead to short-term hair reduction. There is less evidence of long-term benefit.
One small crossover trial suggests that laser treatment is more effective that electrolysis.
Combined oral contraceptives (COCs)
COCs are recommended as first-line treatment for premenopausal women with hirsutism in guidelines and narrative reviews [Claman et al, 2002; Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
COCs decrease plasma testosterone by suppression of luteinizing hormone secretion (thereby reducing ovarian androgen secretion) and by increasing the production of sex hormone-binding globulin (thereby increasing androgen binding and reducing free androgen levels) [Martin et al, 2008].
CKS expert reviewers recommend co-cyprindiol (Dianette®) or a COC containing drospirenone as the preferred COCs for women with hirsutism.
Co-cyprindiol contains the anti-androgen cyproterone acetate, which has been shown to be effective in managing hirsutism. It is licensed for the treatment of moderately-severe hirsutism [ABPI Medicines Compendium, 2008].
Drospirenone also has anti-androgenic properties [Martin et al, 2008]. COCs containing drospirenone (such as Yasmin®) may be an alternative to co-cyprindiol in women with hirsutism, especially as long-term treatment is often necessary.
CKS expert reviewers did not recommend second generation COCs (containing levonorgestrel and norethisterone) and third generation COCs (containing desogestrel, norgestimate, and gestodene) for the management of hirsutism.
COCs containing levonorgestrel and norethisterone are more androgenic and could potentially exacerbate hirsutism [Koulouri and Conway, 2009].
There is some concern that COCs containing desogestrel, norgestimate, and gestodene may have a greater risk of venous thromboembolism than those containing drospirenone, levonorgestrel, or norethisterone, although the absolute risk is is still low (about 25 per 100,000 women per year of use) [BNF 57, 2009].
There is limited evidence on the efficacy of COCs in the management of hirsutism.
Evidence from a Cochrane systematic review (one RCT) suggests that co-cyprindiol is more effective than placebo at reducing hair growth in women with hirsutism.
Evidence from one RCT suggests that COCs containing drospirenone are at least as effective at reducing hair growth as those containing cyproterone acetate.
Evidence from one small RCT with a high drop-out rate suggests there is no difference in clinical outcomes between second and third generation COCs; further studies are needed to confirm this.
Duration of treatment
An Endocrine Society clinical practice guideline suggests a trial of at least 6 months of treatment, based on very low quality evidence [Martin et al, 2008].
The Committee on the Safety of Medicines recommends that co-cyprindiol should be discontinued three or four menstrual cycles after the woman's hirsutism has resolved, due to the risk of serious adverse effects such as thromboembolism [CSM, 2002].
There is a two- to four-fold increase in the risk of venous thromboembolism with co-cyprindiol compared with conventional second-generation COCs, although the absolute risk remains low [Vasilakis-Scaramozza and Jick, 2001; Seaman et al, 2003].
Treatment of relapse when co-cyprindiol is stopped
The advice on whether to continue to use co-cyprindiol continuously or intermittently, or to switch to an alternative COC, is advice based on the opinions of CKS expert reviewers.
Eflornithine
Evidence from small RCTs suggests that eflornithine may improve the appearance of facial hair in the short term (up to 6 months), but its efficacy in the longer term remains unclear.
There is weak evidence that it may be more effective than placebo when combined with laser treatment, in the short term.
Management (postmenopausal)
How should I manage hirsutism in postmenopausal women?
For postmenopausal women:
Discuss cosmetic methods of hair reduction and removal, as these will remain an important part of management.
If hirsutism is mild and does not significantly impact on the woman's quality of life — consider no additional treatment.
If additional treatment is required, consider:
Topical eflornithine, for women with facial hirsutism.
Benefit should be noted in 6–8 weeks, and eflornithine should be discontinued if no benefit is seen within 4 months of starting treatment.
If improvement is seen, continued treatment is necessary to maintain the benefits. Once the cream is discontinued, hair growth returns to pretreatment levels within about 8 weeks.
Referral for initiation of specialist treatment.
Basis for recommendation
Basis for recommendation
Treatment of postmenopausal women
CKS found no evidence specifically on the management of hirsutism in postmenopausal women. Recommendations are based on the opinion of CKS expert reviewers.
Referral
When should I refer a woman with hirsutism?
Refer the woman, if:
Hair growth is of recent onset and rapid progression, there are signs of virilization, hirsutism is particularly severe, or an abdominal or pelvic mass is detected.
There are clinical features suggestive of Cushing's syndrome (such as weight gain in the face [moon face], neck region, upper back, and torso; stretch marks; easy bruising; proximal muscle weakness).
Serum total testosterone concentration is more than 5 nanomol/L.
Hair growth worsens despite treatment.
Treatment has not been effective after 6–12 months.
Basis for recommendation
Basis for recommendation
Androgen secreting tumour
Hair growth of recent onset and rapid progression, signs of virilization, particularly severe hirsutism, and a pelvic or abdominal mass are indications of a more serious underlying cause, such as an androgen-secreting (ovarian or adrenal) tumour.
A high total testosterone concentration may indicate an androgen-secreting tumour [Sathyapalan and Atkin, 2009].
If the total testosterone is normal (< 4.1 nanomol/L) or only slightly increased (< 5 nanomol/L), an androgen secreting tumour can be excluded.
When treatment in primary care has been ineffective
Hirsutism that has failed to respond to treatment in primary care may respond to systemic treatments such as anti-androgens, insulin-sensitizing drugs, and gonadotrophin-releasing hormone agonists [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
Because these drugs are not licensed for the treatment of hirsutism and have potentially serious adverse effects, CKS recommends that they should only be used under specialist supervision.
Treatment in secondary care
What treatments may be used in secondary care?
Systemic treatments that may be used in secondary care include:
Anti-androgens (such as high-dose cyproterone acetate, spironolactone, and flutamide).
5-alpha-reductase inhibitors (such as finasteride).
Insulin-sensitizing drugs (such as metformin and pioglitazone).
Gonadotrophin-releasing hormone analogues (such as goserelin and leuprorelin).
Basis for recommendation
Basis for recommendation
Hirsutism that has failed to respond to treatment in primary care may respond to systemic treatments such as anti-androgens, insulin-sensitizing drugs, and gonadotrophin-releasing hormone agonists [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
Because these drugs are not licensed for the treatment of hirsutism and have potentially serious adverse effects, CKS recommends that they should only be used under specialist supervision.
Weak evidence from a systematic review and meta-analysis (12 randomized controlled trials [RCTs]) suggests that anti-androgens are effective for the treatment of hirsutism [Swiglo et al, 2008].
Compared with placebo, anti-androgens reduced Ferriman–Gallwey scores by 3.9 points (95% CI 2.3 to 5.4).
Weak evidence from a systematic review and meta-analysis (16 RCTs) suggests that insulin-sensitizing drugs have limited efficacy in the treatment of hirsutism [Cosma et al, 2008].
Compared with placebo, insulin sensitizers reduced Ferriman–Gallwey scores by 1.5 points (95% CI 0.3 to 2.8).
There was no evidence of a significant difference between insulin sensitizers and oral contraceptives (weighted mean difference [WMD] 0.5 points; 95% CI 3.9 to 5.0).
Metformin was less effective than both spironolactone (WMD 1.3; 95% CI 0.03 to 2.6) and flutamide (WMD 5.0; 95% CI 3.0 to 7.0).
Evidence
Evidence
Supporting evidence
Evidence on treatments that may be appropriate for primary care has been reviewed. Evidence on treatments that should be initiated in secondary care (such as anti-androgens, insulin-sensitizing drugs, and gonadotrophin-releasing hormone analogues) has not been reviewed in detail.
Combined oral contraceptives
Evidence on combined oral contraceptives for hirsutism
Evidence from a Cochrane systematic review suggests that co-cyprindiol is more effective than placebo at reducing hair growth in women with hirsutism.
Evidence from one randomized controlled trial (RCT) suggests that combined oral contraceptives (COCs) containing drospirenone are at least as effective at reducing hair growth as those containing cyproterone acetate.
Evidence from one small RCT with a high drop-out rate suggests there is no difference in clinical outcomes between second and third generation COCs; further studies are needed to confirm this.
Cyproterone acetate plus ethinylestradiol (co-cyprindiol)
A Cochrane systematic review investigated the effectiveness of cyproterone acetate (CPA), alone or in combination with ethinylestradiol (EE), at reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism [van der Spuy and le Roux, 2003]. In this evidence summary, only the evidence on CPA (2 mg) combined with EE is reviewed.
CPA (2 mg) plus EE compared with placebo (one RCT in 20 people):
At 12 months, there was a significant improvement in hair growth with CPA (2 mg) plus EE compared with placebo (odds ratio [OR] 45, 95% CI 2 to 1007). The wide confidence intervals reflect the small sample size and cast doubt on the precision of this finding.
CPA (2 mg) plus EE compared with CPA (greater than 2 mg) plus EE (one RCT in 113 people):
At 6 months, there were no significant differences between the groups in Ferriman–Gallwey (FG) score or endocrine levels.
Drospirenone plus ethinylestradiol
One open-label uncontrolled trial investigated the efficacy of an oral contraceptive containing drospirenone (DRSP) and EE for the long-term treatment of hirsutism [Batukan and Muderris, 2006]. Fifty women with moderate-to-severe hirsutism, with or without polycystic ovary syndrome, were given drospirenone 3 mg plus ethinylestradiol 30 micrograms (Yasmin®) once a day on days 5–25 of their menstrual cycle, for 12 months.
Total FG score was reduced from 15 (range 8–28) at baseline to 5 (1–13) at 6 months and 3 (0–8) at 12 months.
There was no evidence of a significant change in serum luteinizing hormone, follicle stimulating hormone, estradiol, or dehydroepiandrosterone sulfate levels.
There was a significant decrease in total testosterone (p < 0.0001), free testosterone (p = 0.002), and androstenedione (p = 0.007) levels at 6 months and 12 months.
There was a significant increase in sex hormone-binding globulin levels at 6 months and 12 months (p < 0.0001).
Adverse effects included intermenstrual bleeding (five women), breast tenderness (two women), and mild headache (two women).
Comparing oral contraceptives
One RCT compared the efficacy of a COC containing DRSP 3 mg plus EE 30 micrograms (Yasmin®) with a COC containing CPA 2 mg plus EE 35 micrograms (co-cyprindiol) in 100 women with moderate-to-severe hirsutism (defined as FG score of 8 or more) [Batukan et al, 2007]. Trial medication was taken cyclically (for 21 days, followed by a pill-free period of 7 days) for a total of 12 months. The outcomes were changes in FG score and hormonal assay.
Results were evaluated in 91 women; nine were lost to follow up or became pregnant.
There was significant improvement in the FG score in both groups at 6 months and 12 months, compared with baseline. The percentage reduction was significantly greater in the DRSP/EE group compared with the CPA/EE group at 6 months (70% compared with 57%; p = 0.028) but not at 12 months (80% compared with 81%; p = 0.6).
There was a significant increase in sex hormone-binding globulin and a significant decrease in total testosterone, free testosterone, and androstenedione levels in both groups at 6 months and 12 months. There was no evidence of a significant difference between the two groups in the change in hormone levels.
A second RCT compared the efficacy of a COC containing levonorgestrel 150 micrograms plus EE 30 micrograms (Microgynon 30®, Ovranette®) with a COC containing desogestrel 150 micrograms plus EE 30 micrograms (Marvelon®) in 47 women with moderate-to-severe hirsutism (defined as FG score of 10 or more) [Breitkopf et al, 2003].
Only 10 women (42%) in the levonorgestrel group and 11 women (48%) in the desogestrel group completed 9 months of treatment. Results therefore need to be interpreted with caution.
At 6 months, there was a decrease in FG scores from baseline in both groups (p < 0.001). There was no evidence of a significant difference between the groups at any time point.
Eflornithine
Evidence on eflornithine for hirsutism
Evidence from small randomized controlled trials (RCTs) suggests that eflornithine may improve the appearance of facial hair in the short term (up to 6 months), but its efficacy in the longer term remains unclear. There is weak evidence that, in the short term, it may be more effective than placebo when combined with laser treatment.
Eflornithine compared with placebo
The results of two RCTs comparing eflornithine 13.9% cream with placebo have been combined in two publications; one reporting safety and physician-rated efficacy [Wolf et al, 2007], and one reporting patient-related outcomes [Jackson et al, 2007]. In these studies 596 women with facial hirsutism were randomized to receive eflornithine 13.9% cream or placebo vehicle, applied twice a day for 24 weeks on the face and adjacent areas of the neck affected by unwanted hair growth. Participants were allowed to continue their normal hair removal method.
The primary efficacy outcome was the change from baseline in the Physician's Global Assessment (PGA) rating scale 48 hours after shaving (clear/almost clear, marked improvement, improvement, or no improvement/worse).
At week 24, treatment was considered a success (clear/almost clear or marked improvement on the PGA scale) in 32% of women treated with eflornithine compared with 9% of women treated with placebo (p =< 0.05).
Eight weeks after stopping treatment, the difference between the groups was no longer significant. This was largely due to a return towards baseline in the eflornithine group.
Adverse effects considered to be related to treatment were reported by 46% of women using eflornithine and 40% of women using placebo; none of these were serious. The most common adverse effects were skin-related.
The patient-related outcome measure used was ESTEEM (Exchanges of affection, Social interactions, Time spent removing facial hair, Encountering new people, Engaging in work or school, Minimizing overall bother with facial hair), an instrument that addresses the bother and discomfort felt by women with unwanted facial hair. Each item was rated on a 100 mm visual analogue scale.
There was a significant reduction in the level of overall bother caused by facial hair in women using eflornithine cream compared with placebo (estimated difference 15.8, 95% CI 10.8 to 20.8; p < 0.01).
Women in the eflornithine group also reported reduced levels of discomfort experienced when meeting new people, at work or school, at social gatherings, and during exchanges of affection; and a reduction in the level of bother due to time spent removing hair (p < 0.05) compared with placebo.
Eflornithine combined with laser therapy
Two RCTs have investigated the effects of eflornithine in combination with laser treatment [Smith et al, 2006; Hamzavi et al, 2007].
In the first study, 33 women with unwanted facial hair received laser treatment to their entire upper lip (up to six sessions at 4-week intervals) [Hamzavi et al, 2007]. In addition the women applied eflornithine 13.9% cream to one side of their upper lip and placebo to the other side, twice a day until 2 weeks after the final laser session (that is, half the upper lip was randomized to treatment with eflornithine cream and the other half to treatment with placebo). The primary outcome was change from baseline on the PGA scale; patient global assessment was a secondary outcome.
Data were evaluated in 31 women; one withdrew because of hyperpigmentation that developed after the second laser treatment, and one was lost to follow up.
At the end of the study a grade of clear/almost clear on the PGA scale was achieved in 93.5% of women on the eflornithine sites and 67.9% on the placebo sites (p = 0.021).
Based on their own assessment, 41.9% of women thought that the degree of hair reduction was better with eflornithine, while no women considered hair reduction to be better with placebo; 58.1% of women reported no difference between the two sides.
The advantage with eflornithine was significant after the third laser treatment and was maintained throughout the study; however, it is not known whether the difference continued beyond the 6 months of the study.
In the second study, 64 women with unwanted facial hair received laser treatment to their entire upper lip and chin (at week 2 and week 10) [Smith et al, 2006]. In addition, the women applied eflornithine 13.9% cream to one side of their upper lip and chin and placebo to the other side, twice a day for 34 weeks. Treatment response on chin and upper lip were evaluated separately using the PGA scale, physician rating, and self-assessment by the participant.
Data were evaluated from 54 women (per protocol analysis); two withdrew from the study voluntarily, four were lost to follow up, and protocol violation occurred with four women.
According to the physician rating, at week 34 there was less unwanted facial hair on the side of the lip treated with eflornithine in 12 women and less unwanted facial hair on the side of the lip treated with vehicle in 14 women.
At earlier time points (weeks 6, 10, 16, and 22) there was a significant difference between the two sides in favour of eflornithine.
According to the participants' self-assessment, there was a significant difference favouring eflornithine at all time points.
Laser treatment
Evidence on laser treatment for hirsutism
A Cochrane systematic review provides limited evidence that some laser and photoepilation treatments may lead to short-term hair reduction.
A Cochrane systematic review investigated the effects of epilation with lasers and light sources (photoepilation) on unwanted hair growth [Haedersdal and Gøtzsche, 2006]. The review included 11 randomized controlled trials (RCTs) involving 444 women; the trials were generally of poor methodological quality and most were short term. Primary outcomes were reduction in hair counts, adverse effects, and subjective reduction in hairiness. The methodologies and outcomes were too heterogeneous for meta-analysis to be performed.
Long-term hair reduction (one trial, in 144 people):
The trial used the alexandrite laser, and compared a single treatment with either two or three treatments given at monthly intervals. At 9 months after the final treatment, hair reduction was 55% with three treatments, 44% with two treatments, and 32% with one treatment. The results were difficult to interpret because of methodological issues.
Short-term hair reduction (eight trials, in 259 people):
There appeared to be a short-term effect of approximately 50% hair reduction up to 6 months after treatment with alexandrite and diode lasers.
There was little evidence for an effect of intense pulsed light, neodymium:yttrium-aluminium-garnet (Nd:YAG), or ruby lasers.
Adverse effects:
Pain, skin redness, swelling, burned hairs, and pigmentary changes were infrequently reported.
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of hirsutism, with additional searches in the following areas:
Common underlying causes
Diagnosis and evaluation (including Ferriman–Gallwey scoring system)
Impact on quality of life
Management of peri- or post-menopausal women with hirsutism
Ethnic variation in hair growth
When to refer
The search excluded men, children and hypertrichosis in women.
Search dates
January 2000 – August 2009
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
Hirsutism/
hirsutism.tw
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSH subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
Royal College of General Practitioners
National Guidelines Clearinghouse
Institute for Clinical Systems Improvement
Guidelines International Network
NHS Evidence - National Library of Guidelines
National Health and Medical Research Council (Australia)
Royal Australian College of General Practitioners
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
British Columbia Medical Association
University of Michigan Medical School
Michigan Quality Improvement Consortium
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
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