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.     

Acne keloidalis in women

Acne keloidalis is a chronic scarring folliculitis that most commonly occurs on the scalps of young black men. This disorder is described in two black women who had no evidence of androgen excess. Trauma to scalp hair may have precipitated the condition in one patient. Although it is uncommon, acne keloidalis should be considered a treatable cause of cicatricial alopecia in women.     

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.     

Post-adolescent acne: a review of clinical features

Acne is usually recognized as a disorder of adolescence. However, the referral of patients over the age of 25 years with acne has significantly increased over the past 10 years. The clinical features of 200 patients over the age of 25 years, referred to our department for treatment of acne. were evaluated with a view to establishing possible aetiological factors. There were 152 (76%) women and 48 (24%) men. The mean age of the patients was 35.5 years (range 25-55 years). The acne was mild or moderate in severity, consisting principlly of inflammatory lesion, with mean total acne grade (Leeds Grading Scale) of 1.125 for men and 0.75 for women. Most patients had persistent acne; but true late-onset acne (onset after the age of 25 years) was seen in 28 (18.4%) of women and four (8.3%) of men. Thirty-seven per cent of women had features of hyperandrogenicity. One hundred and sixty-four patients (82%) had failed to respond to multiple courses of antibiotics, and 64 (32%) had relapsed after treatment with one or more courses of isotretinoin. External factors, such as cosmetics. drugs and occupation, were not found to be significant aetiological factor. A family history revealed that 100 (50%) of patients had a first-degree relative with post-adolescent acne. Patients with post-adolescent acne appear to represent an increasingly important population of acne sufferers. External factors do not seem to have a significant aetiological role. Two main clinical groups were identified: those with persistent acne and those with late-onset acne. A minority of women also had features of hyperandrogenicity. These patients, and those with late-onset acne, may represent a subgroup who have underlying abnormalities of ovarian, adrenal or local androgen metabolism, and require separate investigation.     

Androgen metabolism in sebaceous glands from subjects with and without acne.

OBJECTIVE: To determine if there are differences in the activity of 17beta-hydroxysteroid dehydrogenase and 5alpha-reductase (responsible for the production of testosterone and dihydrotestosterone, respectively) in sebaceous glands obtained from men and women with and without acne. DESIGN: Single-center examination of androgen levels and sebaceous gland enzyme activity in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects, consisting of 8 women with acne, 10 women without acne, 8 men with acne, and 8 men without acne. INTERVENTIONS: Single visit for blood sampling and 2 biopsies of forehead skin. MAIN OUTCOME MEASURES: Serum levels of androgens were determined and compared with the activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase in sebaceous glands microdissected from skin samples. RESULTS: No significant differences in the activity of 5alpha-reductase or 17beta-hydroxysteroid dehydrogenase in sebaceous glands according to the presence of acne were noted in either men or women. The activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase was significantly greater in sebaceous glands from men (n = 16) than women (n = 17). The oxidative activity of 17beta-hydroxysteroid dehydrogenase was 2-fold higher in men than women. Serum levels of dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were significantly higher in women with acne than in women without acne. No differences in serum androgen levels were noted in men on the basis of the presence of acne. CONCLUSIONS: Higher serum androgen levels are associated with the presence of acne in women. A role for locally produced androgens in this process, however, cannot be excluded.     

Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women

OBJECTIVES: To determine if insulin-like growth factor 1 (IGF-1) and androgen levels (1) correlate with the presence and severity of acne in adult men and women, and (2) correlate directly with each other and interact in affecting acne. DESIGN: Case-control study and single-center examination of hormone levels in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects (8 women and 8 men with clinical acne, 10 women and 8 men without clinical acne). Clinical acne is defined by a history of persistent acne (acne present on most days for several years), recent acne treatment, and the presence of 10 or more inflammatory acne lesions and 15 or more comedones. INTERVENTIONS: Single visit for serum sampling. MAIN OUTCOME MEASURES: Serum levels of IGF-1 and androgens were determined, adjusted for age, and compared based on the presence or absence of clinical acne using an analysis of covariance. Correlations between hormone levels and acne lesion counts were calculated within each subgroup. Correlations were also calculated between serum levels of IGF-1 and androgens. Further statistical testing was conducted to determine whether IGF-1 or androgens had a greater effect on acne lesion counts. RESULTS: Dehydroepiandrosterone (DHEAS), dihydrotestosterone (DHT), and IGF-1 correlated positively with acne lesion counts in women. Androstenedione and DHEAS correlated with acne lesion counts in men. Although the age-adjusted mean serum levels of IGF-1 were higher in women with clinical acne than in women without clinical acne, this difference did not achieve statistical significance. No difference in IGF-1 level was noted in men based on the presence of clinical acne. In women with clinical acne, IGF-1 correlated with DHT. In men with clinical acne, IGF-1 correlated with DHEAS and androstenedione. In men and women with clinical acne, the effects of androgens on increased acne lesion counts were dependent on the influence of IGF-1. CONCLUSIONS: Increased IGF-1 levels in addition to androgens may influence acne in adult men and women. While IGF-1 appears to have a stronger effect on acne in women, androgens may play a greater role in acne for men. However, in both men and women these hormones are interrelated, possibly owing to reciprocal effects on hormone production.     

痤疮患者血浆雄激素水平及白细胞雄激素受体的测定

为探讨痤疮患者外周血雄激素及白细胞雄激素受体（AR）含量对痤疮发生发展的影响，对35例痤疮患者和35名正常对照采用放射配体结合分析法测定白细胞雄激素受体含量，同时用放射免疫法检测血浆雄激素水平，结果：男性痤疮患者，血浆睾酮仅轻度升高，但其外周血白细胞AR的水平与对照组相比有明显升高（P＜0．05），女性痤疮患者，血浆睾酮水平及外周血白细胞AR水平与对照组相比均明显升高（P＜0．01），雄激素及其受体含量增高在女性痤疮的发病中可能起着重要的作用，痤疮的严重程度与睾酮水平及白细胞AR水平密切相关。     

Androgenetic alopecia in women

Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5alpha reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.     

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).     

Female androgenic alopecia. The 3 alpha,17 beta-androstanediol glucuronide/sex hormone binding globulin ratio as a possible marker for female pattern baldness

Twenty-five women fulfilling the criteria for female alopecia, of either the male pattern baldness type or female pattern baldness type, were evaluated for hormone markers to delineate the clinical baldness patterns. Women with a marked increase in the 3 alpha,17 beta-androstanediol glucuronide/sex hormone binding globulin ratio and low serum sex hormone binding globulin were noted to have female pattern baldness. This pattern of baldness may represent hair loss from the influence of minimal androgen excess on genetically sensitive hair bulbs in the absence of other signs of maximal androgen excess, including hirsutism, acne, or virilism.     

The clinical evaluation of hirsutism

Hirsutism is a disorder of excess growth of terminal hairs in androgen-dependent areas in women. Other cutaneous conditions associated with androgen excess are androgenetic alopecia, acanthosis nigricans, and acne. Hirsutism is often associated with measurably elevated androgen levels, but not in all cases. Androgens in women arise from the ovary and adrenal glands, and peripherally from skin and fat. The most common cause of hirsutism is polycystic ovarian syndrome. Patients with "idiopathic" hirsutism have normal ovulatory cycles and androgen levels. Other causes are late onset congenital adrenal hyperplasia, Cushing's syndrome, and the HAIR-AN syndrome. Pituitary, ovarian, and adrenal tumors are important, but rare causes of hirsutism. A thorough history and examination are important. Laboratory investigation is essential in women with moderate to severe, sudden onset or rapidly progressing hirsutism. Identification of the underlying etiology does not alter management, but detects patients at risk for infertility, diabetes, cardiovascular disease and endometrial carcinoma.     

Therapie der Akne mit Antiandrogenen – Eine evidenzbasierte Übersicht

Background: Increased sebaceous gland activity with seborrhea is one of the major pathogenetic factors in acne. Antiandrogen treatment targets the androgen‐metabolizing follicular keratinocytes and the sebaceous gland leading to sebostasis, with a reduction of the sebum secretion rate of 12.5 – 65 %. Antiandrogens can be classified based on their mechanism of action as androgen receptor blockers, inhibitors of circulating androgens by affecting ovarian function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotropin‐releasing hormone agonists and dopamine agonists in hyperprolactinemia), inhibitors of adrenal function, and inhibitors of peripheral androgen metabolism (5α‐reductase inhibitors, inhibitors of other enzymes). Methods: All original and review publications on antiandrogen treatment of acne as monotherapy or in combination included in the MedLine system were extracted by using the terms “acne”, “seborrhea”, “polycystic ovary syndrome”, “hyperandrog*”, and “treatment” and classified according to their level of evidence. Results: The combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 µg), drospirenone (3 mg)/ethinyl estradiol (30 µg), and desogestrel (25 µg)/ethinyl estradiol (40 µg) for 1 week followed by desogestrel (125 µg)/ethinyl estradiol (30 µg) for 2 weeks showed the strongest anti‐acne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotropin‐releasing hormone agonists, and inhibitors of peripheral androgen metabolism cannot be endorsed based on current knowledge. Low dose prednisolone is only effective in late‐onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. Treatment with antiandrogens should only be considered if none of the contraindications exist. Conclusion: Antiandrogen treatment should be limited to female patients with additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, women with late‐onset or recalcitrant acne who also desire contraception can be treated with antiandrogens as can those being treated with systemic isotretinoin. Antiandrogen treatment is not appropriate primary monotherapy for noninflammatory and mild inflammatory acne.     

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 and the variable response of the pilosebaceous unit to androgen

The pilosebaceous unit (PSU) response to androgen is variable. Certain population of PSU respond to androgen in a distinctive pattern that results in sexual hair development in some, sebaceous gland development in others. Furthermore, androgen excess is variably manifest in women as hirsutism, acne vulgaris, seborrhea, or pattern alopecia. Although sebaceous cells act as intracrine cells, activating pro-hormones to potent androgens that act within the sebocyte, hair follicle metabolism predominantly inactivates testosterone. Androgen action in the sexual hair follicle appears to be mediated by the dermal papilla and possibly, by inducing expression of a specific keratin, hHa7, in the hair medulla. The data do not clearly support a relationship between idiopathic hirsutism, the hirsutism that occurs in the absence of androgen excess, and variations in androgen mechanism of action. Androgens are prominent among the hormones that modulate the biological mechanism regulating the hair cycle. However, the basis for the variable pattern of PSU response to androgen is unclear, as is the basis for the variable development of hirsutism in response to androgen excess and the incomplete reversal of hirsutism by anti-androgen treatment. Improved treatment of hirsutism awaits improved understanding of the nature of the interaction between androgens and other determinants of hair follicle biology.     

Hormonal Profiles and Prevalence of Polycystic Ovary Syndrome in Women with Acne

One of the important etiologic factors in acne is an increase in sebaceous gland activity, which is androgen dependent. Acne is a common manifestation of hyperandrogenemia. Therefore, acne may not only cause cosmetic concern but may also be a sign of underlying disease. In females, the most common cause of hyperandrogenemia is polycystic ovary syndrome (PCOS). The purpose of this study was to determine the hormonal profiles of women with acne and the prevalence of PCOS in women attending the dermatological clinic with acne problems. The diagnostic criteria of PCOS were clinical findings of menstrual disturbances and hyperandrogenism (acne, seborrhea, hirsutism), pelvic ultrasound imaging of PCO (multiple subcapsular ovarian cysts 2–8 mm. in diameter, with dense echogenic stroma), and an elevated luteinizing hormone (LH) to follicle stimulating hormone (FSH) ratio. There were 51 women with acne; 20 regularly menstruating volunteers without acne served as a control group. PCOS was found in 19 out of 51 patients with acne (37.3%) and none of the control group. Twenty acne patients had abnormal menstruation (39.2%). Acne cases had higher mean levels of serum total testosterone (T), free T, dehydroepiandrosterone sulfate (DHEAS) and prolactin (PRL). No statistically significant difference was observed for LH, FSH or sex hormone binding globulin (SHBG). Because of this high prevalence of PCOS in women with acne, all women presenting with acne should be asked about their menstrual pattern and examined for other signs of hyperandrogenemia. Hormonal profile determination as well as pelvic ultrasonography for ovarian visualization should be performed to confirm the diagnosis of PCOS in female acne patients who have menstrual disturbances.     

Ethinylestradiol/Chlormadinone Acetate

Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are common disorders of the pilosebaceous unit (PSU). In some women with hyperandrogenemia, an excess of androgens at the PSU can lead to the development of these dermatological manifestations. These manifestations can cause many psychiatric and psychological implications, such as social fears and anxiety, and can adversely affect quality of life.High androgen levels at the PSU as a possible underlying cause of acne vulgaris, hirsutism, seborrhea and FPHL supports the rationale for using combined oral contraceptives for the management of these conditions in women. The purpose of this review is to describe these dermatological manifestations of the PSU and the management of these conditions through the use of the oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA).EE/CMA 0.03/2mg is a combined monophasic contraceptive pill with anti-androgenic properties. It is approved in Europe for contraception and has been investigated in phase III trials for the treatment of acne.EE/CMA was better than placebo and similar to another low-dose oral contraceptive (ethinylestradiol/levonorgestrel) in improving symptoms of acne in two phase III randomized controlled trials in patients with mild to moderate papulopustular acne. In addition, in trials investigating the contraceptive efficacy of EE/CMA, limited data suggest that there were also improvements in hirsutism, FPHL and seborrhea in small subgroups of patients.EE/CMA has a good safety profile. The most commonly reported adverse events are breast tenderness/pain, headache/migraine and nausea.Evidence in the literature indicates that the use of EE/CMA for the treatment of dermatological disorders under the control of androgens may be a valid treatment option. Further investigation is warranted.     

Ethinylestradiol/Chlormadinone acetate: dermatological benefits

Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are common disorders of the pilosebaceous unit (PSU). In some women with hyperandrogenemia, an excess of androgens at the PSU can lead to the development of these dermatological manifestations. These manifestations can cause many psychiatric and psychological implications, such as social fears and anxiety, and can adversely affect quality of life. High androgen levels at the PSU as a possible underlying cause of acne vulgaris, hirsutism, seborrhea and FPHL supports the rationale for using combined oral contraceptives for the management of these conditions in women. The purpose of this review is to describe these dermatological manifestations of the PSU and the management of these conditions through the use of the oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA). EE/CMA 0.03/2 mg is a combined monophasic contraceptive pill with anti-androgenic properties. It is approved in Europe for contraception and has been investigated in phase III trials for the treatment of acne. EE/CMA was better than placebo and similar to another low-dose oral contraceptive (ethinylestradiol/levonorgestrel) in improving symptoms of acne in two phase III randomized controlled trials in patients with mild to moderate papulopustular acne. In addition, in trials investigating the contraceptive efficacy of EE/CMA, limited data suggest that there were also improvements in hirsutism, FPHL and seborrhea in small subgroups of patients. EE/CMA has a good safety profile. The most commonly reported adverse events are breast tenderness/pain, headache/migraine and nausea. Evidence in the literature indicates that the use of EE/CMA for the treatment of dermatological disorders under the control of androgens may be a valid treatment option. Further investigation is warranted.     

Cutaneous androgen metabolism: basic research and clinical perspectives

The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. As in other classical steroidogenic organs, the same six major enzyme systems are involved in cutaneous androgen metabolism, namely steroid sulfatase, 3beta-hydroxy-steroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, and aromatase. Steroid sulfatase, together with P450 side chain cleavage enzyme and P450 17-hydroxylase, was found to reside in the cytoplasm of sebocytes and keratinocytes. Strong steroid sulfatase immunoreactivity was observed in the lesional skin but not in unaffected skin of acne patients. 3beta-hydroxysteroid dehydrogenase has been mainly immunolocalized to sebaceous glands, with the type 1 being the key cutaneous isoenzyme. The type 2 17beta-hydroxysteroid dehydrogenase isoenzyme predominates in sebaceous glands and exhibits greater reductive activity in glands from facial areas compared with acne nonprone areas. In hair follicles, 17beta-hydroxysteroid dehydrogenase was identified mainly in outer root sheath cells. The type 1 5alpha-reductase mainly occurs in the sebaceous glands, whereby the type II isoenzyme seems to be localized in the hair follicles. 3alpha-hydroxysteroid dehydrogenase converts dihydrotestosterone to 3alpha-androstanediol, and the use of 3alpha-androstanediol glucuronide serum level to reflect the hyperandrogenic state in hirsute women may be a reliable parameter, especially for idiopathic hirsutism. In acne patients it is still controversial if 3alpha-androstanediol glucuronide or androsterone glucuronide could serve as suitable serum markers for measuring androgenicity. Aromatase, localized to sebaceous glands and to both outer as well as inner root sheath cells of anagen terminal hair follicles, may play a "detoxifying" role by removing excess androgens. Pharmacologic development of more potent specific isoenzyme antagonists may lead to better clinical treatment or even prevention of androgen-dependent dermatoses.     

Polycystic ovary syndrome and acne

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.