ArticlePDF Available

Abstract

BACKGROUND: Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective. OBJECTIVES: To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism. SEARCH METHODS: We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism. DATA COLLECTION AND ANALYSIS: Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses. MAIN RESULTS: We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs. AUTHORS' CONCLUSIONS: Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.
A preview of the PDF is not available
... Spironolactone, flutamide and finasteride can be used to treat hirsutism (433), acne and androgenic alopecia (436) but are teratogenic and not approved for this use. Eflornithine hydrochloride cream is used as topical therapy for facial hirsutism (433). It prevents hair growth by inhibiting the anagen phase of hair production. ...
... Hirsutism is the most prevalent symptom in women with NC CAH, but also the most difficult to treat(433). Clinical experience suggests that a combination of oral contraceptives, topical eflornithine and cosmetic treatment (shaving, chemical depilatories, plucking, tweezing, threading, waxing or epilation therapy, electrolysis and intense pulsed light) might be the most effectiveDownloaded from https://academic.oup.com/edrv/advance-article/doi/10.1210/endrev/bnab016/6271518 by University of Michigan user on 11 May 2021 ...
Article
Full-text available
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21- hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000 there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in congenital adrenal hyperplasia with special attention to these new developments.
... In the area of the upper lip, chin, chest, nape, nipple, lumbosacral region, upper abdomen, white line, arms, and medial thighs, androgens stimulate the change of vellus hair into terminal hair -thick, saturated with pigment, extending the phase anagen. On the other hand, in the frontotemporal area and on the top of the head, miniaturization of the hair follicles occurs under the influence of androgens, with the shortening of the anagen phase [18]. ...
Article
Full-text available
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by numerous hormonal and metabolic disturbances, among which hyperandrogenism, insulin resistance, as well as disruption in carbohydrate and lipid metabolism play an important role. The study aimed to present the PCOS, taking into account the skin lesions often present in the disorder. The collected information concerns the mechanism and purposes for the development of clinical symptoms as a result of disturbances in a female body. The diagnosis of PCOS is determined by the presence of two out of three criteria: excess of androgen hormones, anovulation or their rarity, and the image of polycystic ovaries on ultrasound, while excluding other disease entities.
... While the available data are conflicting, major studies note that mood disorders of various types are not a proficient reason to avoid the use of hormonal methods of contraception [16]- [18]. ...
Article
Full-text available
The safety of hormonal contraceptives (HCs) has been discussed in multiple studies in the medical literature. HCs are effective contraception methods and are commonly prescribed worldwide. However, Women have many misconceptions leading them to avoid using HCs even when they are indicated. Therefore, the aim of this review was to discuss the most common questions and concerns in an objective manner regarding weight gain, mood changes, libido, the time needed to return to fertility after discontinuation, the effects of simultaneous use of antibiotics and some of the most common side effects. HCs were found to be beneficial in reducing symptoms of many physiological and non-physiological conditions including primary dysmenorrhea, heavy menstrual bleeding, hirsutism, and Endometriosis- related pain. HCs are safe and the available evidence support their usage.
... Utilizing other therapeutic plants, can open another window for the scientists in this ield. As indicated by the standards of clinical preliminaries and Jadad scale, the nature of these four investigations was acceptable and the counter androgenic impacts of mint were more articulated than different teas (van Zuuren et al., 2015). ...
Chapter
Within person randomized trials (e.g., trials using within subject controls) are often employed for conditions that affect paired organs or two or more body sites of a person. In within person trials, the paired organs or body sites of a person receive two competing interventions either concurrently or sequentially, and the outcome measures are taken from each of paired organs or body sites. The within person design is a useful and efficient tool because comparisons between two interventions are made within the same person, thus removing the inter-person variability. Within person trials are most commonly conducted in ophthalmology, dentistry, and dermatology. However, within person trials pose some challenges including the possible bias from the carry across effect, the difficulty in recruitment subjects with bilateral disease of similar characteristics, and the limitation in generalization of the trial results. The within person correlations in outcome measures also complicate the sample size determination and statistical analyses of trial data from within person trials. This chapter describes the rationale and requirements for employing within person design, the considerations in designing within person trials in various disease specialty areas. The appropriate methods for sample size calculation and the statistical analysis for within person trials are also described. Real trials are used throughout the chapter to demonstrate the trial design considerations, sample size calculation, and statistical analysis of correlated data from within person trials.
Article
Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman’s life, the clinical picture, diagnosis, and treatment tactics of the disease are different. PCOS has a complex of reproductive, metabolic and psychological characteristics. The target audience of these clinical recommendations are obstetrician-gynecologists, endocrinologists, general practitioners, general practitioners. In these clinical guidelines, all information is ranked according to the level of persuasiveness of recommendations and the reliability of evidence, depending on the number and quality of studies on this issue.
Article
Diseases (conditions) associated with excess production of androgens in the female body or an increase in the sensitivity of hormone-dependent organs to them are united by the concept of ‘hyperandrogenic syndrome’. Its variants range from isolated skin lesions and its derivatives to systemic diseases accompanied by a high risk of menstrual irregularities, infertility, metabolic disorders, cardiovascular pathology, and carcinogenesis. The management of patients with hyperandrogenism is carried out by gynecologists, endocrinologists, dermatologists, general practitioners, but in real life, interaction between representatives of certain medical specialties, unfortunately, is rarely observed. As a result, the treatment of patients with hyperandrogenism is sinning with polypharmacy, inappropriate prescribing and ignoring the current needs of women. The situation is aggravated by the fact that there are practically no drugs annotated for the treatment of external manifestations of hyperandrogenism, and the number of drugs that can have a multifaceted effect is small. One of the strategies that can reduce the drug load and solve several problems at once to compensate for androgen-dependent dermopathies and maintain health in patients with hyperandrogenism is the appointment of combined hormonal contraception. The determining factors in the choice of a hormonal contraceptive for women with hyperandrogenism should be the presence of the antiandrogenic effect of the progestin in the composition of the drug and the safety of long-term use of the drug.
Article
The approach to hyperandrogenism in women varies depending on the woman's age and severity of symptoms. Once tumorous hyperandrogenism is excluded, the most common cause is PCOS. Hirsutism is the most common presenting symptom. The woman's concern about her symptoms plays an important role in the management of disease. Although measurement of testosterone is useful in identifying an underlying cause, care must be taken when interpreting the less accurate assays that are available commercially. Surgical resection is curative in tumorous etiologies, whereas medical management is the mainstay for non-tumorous causes.
Article
Several existing unconditional methods for setting confidence intervals for the difference between binomial proportions are evaluated. Computationally simpler methods are prone to a variety of aberrations and poor coverage properties. The closely interrelated methods of Mee and Miettinen and Nurminen perform well but require a computer program. Two new approaches which also avoid aberrations are developed and evaluated. A tail area profile likelihood based method produces the best coverage properties, but is difficult to calculate for large denominators. A method combining Wilson score intervals for the two proportions to be compared also performs well, and is readily implemented irrespective of sample size. © 1998 John Wiley & Sons, Ltd.
Article
Several existing unconditional methods for setting confidence intervals for the difference between binomial proportions are evaluated. Computationally simpler methods are prone to a variety of aberrations and poor coverage properties. The closely interrelated methods of Mee and Miettinen and Nurminen perform well but require a computer program. Two new approaches which also avoid aberrations are developed and evaluated. A tail area profile likelihood based method produces the best coverage properties, but is difficult to calculate for large denominators. A method combining Wilson score intervals for the two proportions to be compared also performs well, and is readily implemented irrespective of sample size. © 1998 John Wiley & Sons, Ltd.
Article
GnRH agonists (GnRH-A) have been used for the treatment of hirsutism in women with ovarian hyperandrogenism. However, significant side-effects, including vasomotor symptoms and bone loss, have prevented the long term use of this therapy. In this study, we evaluated the effects of low dose (physiological) estrogen replacement on the side-effects and clinical and hormonal parameters of 22 hirsute women with ovarian hyperandrogenism when treated with a long-acting GnRH-A, Decapeptyl. Ten patients with Ferriman-Gallwey (FG) scores averaging 13.4 ± 1.5 were randomly assigned to be treated with Decapeptyl alone (3.75 mg, im, every 28 days for 6 months), and 12 other patients with FG scores averaging 13.3 ± 1 received Decapeptyl with estrogen (conjugated equine estrogens, 0.625 mg) for 21 days and medroxyprogesterone acetate (10 mg) for 10 days (days 12-21). After 6 months, LH was suppressed in both groups, whereas FSH was significantly reduced only in the group receiving GnRH-A with estrogen (2.5 ± 4 vs. 4.8 ± 0.6 IU/L; P < 0.01). Serum androgen levels were reduced in both groups, although the reduction of testosterone and unbound testosterone was greater in the group receiving hormonal replacement [1.73 ± 0.3 vs. 2.57 ± 0.4 nmol/L for testosterone (P < 0.05); 8.3 ± 1 vs. 14.6 ± 2.8 pmol/L for unbound testosterone (P < 0.05)]. The reduction in hirsutism scores was greater with hormonal replacement (FG scores, -4.1 ± 0.3 vs. -2.5 ± 0.3; P < 0.05), whereas the polycystic appearance of ovaries by ultrasound was decreased in both groups. Amenorrhea and vasomotor symptoms were observed only with GnRH-A alone. Serum osteocalcin rose significantly with GnRH-A alone, reflecting a change in bone turnover (0.49 ± 0.05 to 0.64 ± 0.09 nmol/L; P < 0.05), but was unchanged with hormonal replacement. Patients receiving hormonal replacement had treatment extended to 1 yr. A further improvement of hirsutism, with scores dropping into the normal range (4.9 ± 0.7), as well as a normalization of ovarian morphology were evident at this time. In conclusion, low dose (physiological) estrogen replacement may enhance the effects of GnRH-A treatment, while preventing most of the side-effects encountered with GnRH-A alone. This may allow more prolonged treatment, which is necessary for hirsutism.