Correlation between endocrinological parameters and acne severity in adult women

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women >17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels (p<0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes.     

IDIOPATHIC HIRSUTISM: REVIEW OF THE CONCEPT

Patients with idiopathic hirsutism form a heterogeneous group with a number of hormonal abnormalities, those most consistently demonstrated being an increase in free plasma testosterone levels, an increase in testosterone production rate and a decrease in sex hormone binding globulin levels. In most patients the principal source of androgen excess appears to he ovarian. Some have additional adrenal hyperandrogenism but a pure adrenal source is probably rare. Idiopathic hirsutism may be regarded as part of a clinical spectrum of ovarian hyperandrogenism. The ovarian patholoqy present in the majority of cases is probably that of polycystic ovarian disease. This may be a genetically determined disorder with a modified dominant form of inheritance. Ethnic and familial variations in amount and type of hair growth in androgen dependent sites undoubtedly do occur. Nevertheless the finding of normal plasma androgens in many women labelled ethnically or constitutionally hirsute may be the result of inappropriate blood sampling and failure to measure free plasma testosterone or testosterone production rate.     

Medical treatment of hirsutism

Hirsutism is usually the result of an underlying adrenal, ovarian, or central endocrine abnormality mainly due to polycystic ovary syndrome but may also be idiopathic or drug induced. The aim of medical treatment of hirsutism is to rectify any causal hormonal balance, slow down or stop excessive hair growth, and improve the aesthetic appearance of hirsutism, thereby positively affecting the patient's quality of life. Today, for the majority of women, a monotherapy with oral contraceptives that have antiandrogenic activity is recommended as a first-line treatment for hirsutism. Combining an oral contraceptive pill with an antiandrogen is recommended if clinical improvement of hirsutism is insufficient after 6-9 months' monotherapy. In women who present with hirsutism, hyperandrogenism, and insulin resistance, insulin sensitizers are effective for the hirsutism as well as the hyperinsulinemia, hyperandrogenism, and infertility but there is no convincing evidence that they are effective for hirsutism alone. Topical eflornithine is a medical therapy that can be a useful adjuvant for hirsutism when used in conjunction with systemic medications or with laser/photoepilation.     

Management of Hirsutism

This review reports our own experience with, and literature studies of, the pharmacological management of hirsutism in women with hyperandrogenism (polycystic ovary syndrome) or with normal serum androgen levels and regular ovulatory menstrual cycles (idiopathic hirsutism). Treatment consists of suppressing ovarian or adrenal androgen secretion, or blocking androgen actions in the skin. The major drugs used are gonadotropinreleasing hormone (GnRH) agonists, combined oral contraceptives (COCs), and steroidal (cyproterone acetate and spironolactone) or nonsteroidal (flutamide and finasteride) antiandrogens. GnRH agonists, suppressing the pituitary, decrease androgen and estradiol secretion and improve severe hirsutism. To avoid estrogen deficiency problems, ‘add back’ therapy with estrogen-progestogen or COCs is advisable. This method of treatment is complicated and expensive, limiting its use to severe forms of ovarian hyperandrogenism with hyperinsulinemia. The third-generation COCs, containing new progestogens or cyproterone, have very restricted effectiveness in the short term (6 cycles), but their long term use (>12 cycles) cures mild-to-moderate hirsutism and improves severe hirsutism. As well as suppressing gonadotropins and ovarian androgen steroidogenesis, these formulations decrease free testosterone levels and may also decrease adrenal androgen production. In women being treated with antiandrogens, COCs are important to provide control of the menstrual cycle and contraception. Cyproterone, a progestational agent, inhibits gonadotropin secretion and blocks androgen action. It is used in COCs or in a reverse sequential regimen. In the latter, it is very effective in the short term treatment of hirsutism. Spironolactone blocks androgen receptors. Its effectiveness in hirsutism is dosage-dependent: low dosages are less active than other antiandrogens, whereas high dosages (200 mg/day) are very effective at the cost of several adverse effects (particularly dysfunctional uterine bleeding), but the concomitant use of a COC may prevent these. Flutamide is a pure antiandrogen that blocks androgen receptors and inhibits hair growth. It is very effective in treating hirsutism within 6 to 12 months. Dry skin is very frequent during treatment with flutamide, and hepatotoxicity is possible at high dosages. Finasteride, a 5α-reductase type 2 inhibitor, is the least effective antiandrogen, but a dosage of 5 mg/day decreases hirsutism without adverse effects. Pregnancy must be avoided during therapy with antiandrogens because of the possible risk of abnormal development of a male fetus. Antiandrogens, especially flutamide (250 to 500 mg/day) and cyproterone (12.5 to 50 mg/day in a reverse sequential regimen), alone or in association with COCs, seem to be the most effective agents for the treatment of hirsutism.     

SAHA综合征研究进展

SAHA综合征是女性患者雄激素功能过强而引起的一组皮肤症候群,主要临床特征为皮脂溢、痤疮、多毛及雄激素脱发。该综合征可在一系列疾病导致的外周雄激素水平增高基础上发生,也可由毛囊皮脂腺组织对正常循环雄激素水平过于敏感的应答导致。临床分为特发型,卵巢型,肾上腺型,高催乳素型和高雄激素一胰岛素抵抗一黑棘皮型。应在明确病因和临床类型的基础上个体化治疗。     

Hirsutes I: Diagnosis

Hirsutes, the coarse, androgen-dependent growth of hair in women, is a common problem faced by doctors. Whether a woman presents to a clinician or not depends on cultural and racial factors. The clinician must differentiate normal biological variation from cases of hirsutes. In the vast majority of cases, androgen excess is only found locally at the level of the hair follicle; that is, the hirsutism is idiopathic. Important causes of androgen excess, such as an ovarian tumour, need to be excluded. Part one describes the causes of hirsutism and how to differentiate them using history, examination and investigation.     

Congenital adrenal hyperplasia and acne in male patients

Seborrhoea is one pathogenic factor for acne. Androgens induce sebum production, and excess androgen may provoke or aggravate acne. In women an androgen disorder is frequently suspected when acne is accompanied by hirsutism or menstrual irregularities. In men acne may be the only symptom of androgen excess. We report three male acne patients in whom hormonal screening revealed irregularities of androgen metabolism suggestive of late-onset congenital adrenal hyperplasia and who benefitted from low-dose glucocorticoids. Disorders of androgen metabolism may influence acne not only in women, but also in men, and these patients may benefit from low-dose glucocorticoid therapy.     

Adrenal androgen abnormalities in women with late onset and persistent acne

Androgens are an essential prerequisite for the development of acne. The present study was undertaken to characterize the androgen status of women with late onset and persistent acne only and, using the dexamethasone (dex) suppression test, to identify the source(s) of the androgen excess. We measured serum levels of total testosterone (T), free testosterone (FT), androstenedione ( ⁴A), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding globulin (SHBG) in 34 healthy control subjects, in 34 women with mild acne and in 29 women with moderate or severe acne. Serum FT, DHT and DHEA-S levels in patients of both acne groups were significantly higher than those in the control subjects. The other hormone levels showed no significant differences between patients and control subjects, and there were no significant differences between the two acne groups in any of the androgen levels. In order to evaluate the ovarian and adrenal contributions to serum androgens in the acne patients, the serum levels of ⁴A, T, DHT and DHEA-S were measured prior to and following 2 weeks of dex therapy. Following the dex test, the DHT and T of adrenal origin were significantly higher in the acne patients than in the control subjects. These results suggest that, in acne patients, hyperandrogenaemia is likely to develop as a result of adrenal androgen excess. In addition, since abnormally high androgen levels are frequently seen in late onset and persistent acne, it seems that this condition is likely to be a sign of hyperandrogenism.     

What every physician should know about polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne, and pattern alopecia. It is a heterogeneous syndrome of hyperandrogenic anovulation that is typically due to intrinsic ovarian dysfunction, which is often aggravated by insulin-resistant hyperinsulinemia with its risks of diabetes mellitus and metabolic syndrome and their complications. Because there are many pitfalls to androgen assays, evaluation for hyperandrogenemia is suggested in women with moderate or severe hirsutism or hirsutism equivalents, menstrual irregularity, acanthosis nigricans, or intractable obesity. An endocrinologic work-up is necessary to rule out other hyperandrogenic disorders that require specific therapy (e.g., virilizing tumors, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, and Cushing's syndrome). Ultrasonography helps in the differential diagnosis and may demonstrate the polycystic ovaries that have recently been vetted as an alternative to oligo-anovulation as a diagnostic criterion. Management of PCOS is determined by symptomatology. For those women not desiring pregnancy, the most common therapies are oral contraceptive pills, antiandrogens (contraindicated in the absence of adequate contraception), and insulin-lowering treatments (which have little effect on hirsutism).     

Is there a role for insulin resistance in nonobese patients with idiopathic hirsutism?

Background  Hirsutism is the presence of terminal hairs in women in a male-like pattern. It may result from various causes of androgen excess or may be idiopathic. Controversies exist concerning the presence of insulin resistance in idiopathic hirsutism (IH) or if it is a manifestation of a high body mass index (BMI).
Objectives  To assess insulin resistance in nonobese patients with IH.
Methods  The study included three groups of age- and BMI-matched nonobese women: 30 patients with IH (group 1), 20 patients with hirsutism associated with polycystic ovary syndrome (PCOS) (group 2) and 20 healthy controls (group 3). The pattern of obesity based on waist to hip ratio (WHR), and insulin resistance based on fasting insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were assessed in all the groups.
Results  Sixteen patients with IH and 17 with PCOS had insulin resistance with statistically significant differences in fasting insulin levels and HOMA-IR between the three groups, between patients with IH and healthy controls and between patients with PCOS and healthy controls; there were no significant differences between patients with IH and patients with PCOS. When classified according to the pattern of obesity, 23 patients in group 1, 17 in group 2 and two in group 3 had a WHR ≥ 0·85 (android obesity) with highly significant higher values of fasting insulin levels and HOMA-IR in patients with a WHR ≥ 0·85 when compared with those with a WHR < 0·85.
Conclusions  Insulin resistance occurs in nonobese patients with IH and appears to be related to android obesity.     

Assessment of androgens in women with adult-onset acne

BACKGROUND: Acne is generally recognized as a disorder of young adults; however, the referral of patients aged over 25 years with acne is increasing. Disturbed androgen production in the ovaries or adrenal gland and impaired plasma transport of androgens in women with adult-onset acne or acne associated with hirsutism have been described. METHODS: Thirty-five white women with adult-onset acne (onset after the age of 25 years) and hirsutism (A + H), 35 white women with adult acne without hirsutism (A - H), and 35 age-matched white female controls were recruited in this case-control study. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dihydroepiandrosterone sulfate (DHEA-S), and sex hormone binding globulin (SHBG) were determined in all patients and compared. RESULTS: The mean SHBG, free androgen index (FAI), and DHEA-S were significantly different between A + H and control subjects. The only significant difference between A - H and control subjects was observed for DHEA-S. CONCLUSION: DHEA-S plays a key role in the pathogenesis of adult-onset acne. Measurement of circulating androgens, including DHEA-S, especially in patients presenting with adult-onset acne and hirsutism, is helpful, and patients with elevated levels can benefit from hormonal therapy.     

HIRSUTISM IN KASHMIR: AN ETIOLOGICAL STUDY

Background:

Hirsutism refers to the presence of terminal hairs at the body sites under androgenic control. Various factors, including genetic makeup and hormonal status, influence the rate and pattern of hair growth at these sites.

Purpose:

To study the pattern of hirsutism in Kashmir.

Materials and Methods:

Thirty five consecutive patients of hirsutism were included in the study. After detailed history taking, physical examination and relevant investigations, scoring of hirsutism was done using the Ferriman Gallwey (FG) scoring system.

Findings:

The FG score ranged from 10-34. Twenty patients had associated menstrual abnormalities. Polycystic ovarian syndrome (PCOS) was diagnosed in four patients, hypothyroidism in two and congenital adrenal hyperplasia (CAH) in one. The rest of the patients had idiopathic hirsutism.

Conclusion:

Idiopathic hirsutism was the most common category, whilst PCOS, hypothyroidism and CAH were also seen.     

Acne: effect of hormones on pathogenesis and management

In the pathogenesis of acne, androgen hormones play a crucial role. In the treatment of acne, hormonal therapies provide valuable alternatives to standard modalities in selected women. Although numerous factors contribute to the development of acne, the requirement for androgens is absolute and is one that allows for effective treatments in women through inhibition of androgen expression. The two prerequisites for androgen expression at the level of the pilosebaceous unit are the presence of androgen in the form of either testosterone or dihydrotestosterone; and functioning androgen receptors. A third component may be the metabolism of androgen precursors to active androgens within pilosebaceous units. Hormonal treatment of hyperandrogenism (acne, hirsutism, androgenetic alopecia) such as that seen in polycystic ovary syndrome, centers on reduction of circulating androgen levels and androgen receptor blockade. Combination oral contraceptives represent the primary treatment modality for reducing circulating androgens from ovarian and, to a lesser degree, adrenal sources. Newer formulations may also have clinically significant androgen receptor blocking and 5alpha-reductase inhibiting effects. Newer oral contraceptives have high safety profiles and are used widely internationally for this purpose. Androgen receptor blockers currently in use include spironolactone, cyproterone acetate, and flutamide. Androgen receptor blockers are frequently combined with oral contraceptives to achieve optimal results in selected women. In women with adrenal hyperplasia, low-dose corticosteroids may be added to reduce adrenal androgen precursors. Inhibition of enzymes of androgen metabolism in the pilosebaceous unit remain largely investigational in the treatment of acne, although the benefit of 5alpha-reductase (type 2) inhibition is established in androgenetic alopecia in men. This article reviews the essentials of hormonal influence in acne pathogenesis, discusses the hormonal therapies most utilized in the treatment of acne, and the pre-treatment evaluation of women in whom hormonal therapies are being considered.     

Hirsutism: An Evidence-Based Treatment Update

Background

Hirsutism has a relatively high prevalence among women. Depending upon societal and ethnic norms, it can cause significant psychosocial distress. Importantly, hirsutism may be associated with underlying disorders and co-morbidities. Hirsutism should not simply be looked upon as an issue of cosmesis. Patients require appropriate evaluation so that underlying etiologies and associated sequelae are recognized and managed. Treatment of hirsutism often requires a multidisciplinary approach, and a variety of physical or pharmacologic modalities can be employed. Efficacy of these therapies is varied and depends, among other things, upon patient factors including the underlying etiology, hormonal drive, and local tissue sensitivity to androgens.

Objective

The objective of this paper is to review and summarize current evidence evaluating the efficacy of various treatment modalities for hirsutism in premenopausal women.

Methods

Online databases were searched to identify all relevant prior systematic reviews and meta-analyses as well as recently published (2012–present) randomized controlled trials (RCTs) on hirsutism treatment.

Results

Four recently published RCTs met criteria for inclusion in our review. In addition, one meta-analysis and one systematic review/treatment guideline were identified in the recent literature. Physical modalities and oral contraceptive pills (OCPs) remain first-line treatments. Evidence supports the use of electrolysis for permanent hair removal in localized areas and lasers (particularly alexandrite and diode lasers) for permanent hair reduction. Topical eflornithine can be used as monotherapy for mild hirsutism and as an adjunct therapy with lasers or pharmacotherapy in more severe cases. Combined OCPs as a class are superior to placebo; however, antiandrogenic and low-dose neutral OCPs may be slightly more efficacious in improving hirsutism compared with other types of OCPs. Antiandrogens are indicated for moderate to severe hirsutism, with spironolactone being the first-line antiandrogen and finasteride and cyproterone acetate being second-line antiandrogens. Due to its risk for hepatotoxicity, flutamide is not considered a first-line therapy. If used, the lowest effective dose should be administered with careful monitoring of liver enzymes. Monotherapy with an insulin sensitizer does not significantly improve hirsutism. While insulin sensitizers improve important metabolic and endocrine aberrations in polycystic ovary syndrome, they are not recommended when hirsutism is the sole indication for use. Lifestyle modification counseling is recommended. Gonadotropin-releasing hormone analogs and glucocorticoids are only recommended in specific circumstances. Additional therapies without sufficient supportive evidence of efficacy are ovarian surgery, statins (HMG-CoA reductase inhibitors), and vitamin D supplementation.

Limitations

In general, most therapies garner recommendations that are weak (where the estimates of benefits versus risks of therapy are either closely balanced or uncertain) and are based on low- to moderate-quality evidence.

Conclusions

Risks and benefits of treatment must be carefully considered and discussed with the patient. Expectations for efficacy should be appropriately set. A minimum of 6 months is required to see benefit from pharmacotherapy and lifelong treatment is often necessary for sustained benefit.     

The diagnosis of androgenetic alopecia in children: Considerations of pathophysiological plausibility

Androgenetic alopecia (AGA), one of the most common causes of hair loss in men and women, is an infrequent cause of alopecia in children. In AGA, patients generally start noticing hair thinning after the onset of puberty due to progressive miniaturisation of the hair follicle which leads to vellus transformation of terminal hair. However, the occurrence of prepubertal AGA has rarely been reported in the literature. The pathophysiology of AGA is tightly linked to androgen hormones; prepubertal children do not usually produce significant amounts of adrenal or gonadal androgens. When it does occur, an underlying abnormality should be suspected. Secondary causes of AGA must be excluded when evaluating a patient before the appearance of puberty. Premature puberty, polycystic ovarian syndrome and other causes of hyperandrogenism can present with hair loss in an androgenetic pattern. This article reviews the normal physiology of androgen hormones and their role in the pathophysiology of childhood AGA.     

Female Androgenetic Alopecia: An Update on Diagnosis and Management

Female androgenetic alopecia (FAGA) is a common cause of non-scarring alopecia in women. The onset may be at any age following puberty and the frequency increases with age. Clinically, it shows a diffuse hair thinning over the central scalp, while the frontal hairline is usually retained. FAGA can have a significant psychological impact, leading to anxiety and depression. For this reason, early diagnosis is very important to stop the progression of the disease. The sex hormonal milieu is the main pathogenetic mechanism studied in FAGA. The role of androgens is not clearly defined and only one-third of women with FAGA show abnormal androgen levels. Endocrinological diseases with hyperandrogenism associated with FAGA comprise polycystic ovarian syndrome (PCOS), hyperprolactinemia, adrenal hyperplasia and, rarely, ovarian and adrenal tumours. Usually the diagnosis of FAGA is made clinically. A complete clinical examination and a blood examination can reveal other signs of hyperandrogenism. Trichoscopy shows the typical hair miniaturization. A scalp biopsy can be useful when the clinical evaluation does not provide a definitive diagnosis or when cicatricial alopecias with hair loss in the distribution of FAGA or alopecia areata are suspected. FAGA is a slowly progressive disease. The goal of therapy is to stop the progression and to induce a cosmetically acceptable hair regrowth. The most important drugs are topical minoxidil and oral anti-androgens. The purpose of this review is to provide an update on FAGA and to create a guideline on diagnosis and management of this frequent hair disease, not always easily recognizable from cicatricial alopecias with a similar distribution.

     

Polycystic ovary syndrome: a dermatologic approach

Polycystic ovary syndrome (POS) is one of the most common endocrine abnormalities affecting women of reproductive age. It is a cause of significant social embarrassment and emotional distress. The pathogenesis of the disease is not yet fully understood, but it is thought to be a complex multigenic disorder, including abnormalities in the hypothalamic-pituitary axis, steroidogenesis, and insulin resistance. The main diagnostic findings of the syndrome are: hyperandrogenism, chronic anovulation and polycystic ovarian morphology seen on ultrasound. Hyperandrogenism is generally manifested as hirsutism, acne, seborrhea, androgenic alopecia and, in severe cases, signs of virilization. Treatment may improve the clinical manifestations of excess androgen production, normalize menses and ameliorate metabolic syndrome and cardiovascular complications. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. Early diagnosis and the consequent early treatment may prevent metabolic complications and emotional distress that negatively impact the patients' quality of life.     

Dermatology of androgen-related disorders

Hyperandrogenism in women can be caused by various conditions, the most prevalent of which is polycystic ovary syndrome. Common dermatologic manifestations of hyperandrogenism include hirsutism, acne, acanthosis nigricans, and androgenic alopecia. Hirsute women often have increased activity of 5 alpha-reductase, the enzyme that converts the androgen testosterone to its active metabolite, in hair follicles. Likewise, androgens affect the formation of acne by increasing sebum production from sebaceous glands in the skin. The diagnosis of polycystic ovary syndrome includes a complete history, physical examination with emphasis on evidence of androgen excess, and appropriate laboratory investigation to exclude other causes of hyperandrogenism. Treatments for the dermatologic conditions of hyperandrogenism include lifestyle modification, oral contraceptives, antiandrogens, and insulin-sensitizing medications.     

Evaluation of plasma testosterone: Which test and when?

Biochemical evaluation of androgenicity in men and women requires the determination of plasma testosterone (T). Because essentially only nonspecifically bound T appears to be available to tissues and to be bioactive (Bio-T), it may be required, in some instances, to determine the Bio-T fraction (free T [FT] and albumin-bound T). Surprisingly, a very important interlaboratory variation in T levels does exist and the lack of precision of current methods does not allow accurate measurement of T levels in women or prepubertal boys. Thus, each laboratory should establish its own range of normal values. As to parameters of FT or Bio-T, kits for direct measurement of FT are unreliable. Equilibrium dialysis, the gold standard of FT, is not suited for clinical routine, whereas the FT index (T/sex hormone-binding globulin [SHBG]) is a reliable parameter of FT in women only; calculation of FT and Bio-T (from T, SHBG, and albumin concentration) yields reliable results, but the absolute values depend on the association constants of SHBG and albumin for T used. In men (F)T is mainly used to confirm the clinical diagnosis of hypogonadism or to modulate androgen treatment. In otherwise healthy hypogonadal men, measurement of total T will suffice, but in patients with conditions affecting binding proteins (eg, thyroid or liver pathology, nephrotic syndrome, obesity) measurement of Bio-T may be required. In women, androgen measurement is generally required to evaluate androgen excess (eg, polycystic ovary syndrome, ovulatory dysfunction, hirsutism).     

Evaluation of plasma testosterone: Which test and when?

Biochemical evaluation of androgenicity in men and women requires the determination of plasma testosterone (T). Because essentially only nonspecifically bound T appears to be available to tissues and to be bioactive (Bio-T), it may be required, in some instances, to determine the Bio-T fraction (free T [FT] and albumin-bound T). Surprisingly, a very important interlaboratory variation in T levels does exist and the lack of precision of current methods does not allow accurate measurement of T levels in women or prepubertal boys. Thus, each laboratory should establish its own range of normal values. As to parameters of FT or Bio-T, kits for direct measurement of FT are unreliable. Equilibrium dialysis, the gold standard of FT, is not suited for clinical routine, whereas the FT index (T/sex hormone-binding globulin [SHBG]) is a reliable parameter of FT in women only; calculation of FT and Bio-T (from T, SHBG, and albumin concentration) yields reliable results, but the absolute values depend on the association constants of SHBG and albumin for T used. In men (F)T is mainly used to confirm the clinical diagnosis of hypogonadism or to modulate androgen treatment. In otherwise healthy hypogonadal men, measurement of total T will suffice, but in patients with conditions affecting binding proteins (eg, thyroid or liver pathology, nephrotic syndrome, obesity) measurement of Bio-T may be required. In women, androgen measurement is generally required to evaluate androgen excess (eg, polycystic ovary syndrome, ovulatory dysfunction, hirsutism).