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Hyperandrogenism or hyperandrogenemia are medical conditions characterized by excessive levels of androgens in the periphery or systemically. Clinical manifestations of hyperandrogenism include hirsutism, seborrhea, acne, androgenetic alopecia, and virilization. Hirsutism, defined as excessive growth of terminal hair in women in a male-like pattern, is the most commonly used clinical diagnostic criterion of hyperandrogenism and is determined by using a standardized scoring system of hair growth. Acne and alopecia are further common androgenic skin changes and might be observed without hirsutism in some women. Clitoris hypertrophy, increase of muscle mass, irregular menstrual cycle, and metabolic syndrome can also accompany this condition. Among others polycystic ovary syndrome (PCOS), Cushing disease, and late-onset adrenogenital syndrome belong to the most frequent causes of hyperandrogenemia. Virilization is a relatively uncommon feature of hyperandrogenemia and its presence often suggests an androgen-producing tumor. Management of symptoms include the use of antiandrogens such as cyproterone acetate, spironolactone, and flutamide. A thorough history, a focused clinical examination and an interdisciplinary approach together with gynecologists and endocrinologists are extremely helpful in the diagnostic evaluation and therapy of patients with suspected hyperandrogenism.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of childbearing age. Due to hyperandrogenism and chronic anovulation affected women may suffer from hirsutism, androgenetic alopecia, acne, menstrual disturbance and sub-/infertility. Furthermore underlying insulin resistance promotes hyperandrogenemia, overweight and risk for diabetes. Therefore, routine evaluation of glycemic status is recommended. Treatment strategies are based on therapeutic lifestyle changes and focus on patient-important complaints. First line pharmacologic treatment for infertility in women with PCOS is letrozole. Clomiphene and metformin can be used alternatively with lower success rates. Women seeking medical advice for hyperandrogenism can be offered oral contraceptive pills with the lowest effective estrogen dose without any preference of a certain gestagen. Risk for deep vein thrombosis should be taken into account when choosing estrogen dose and type of gestagen. Antiandrogen substances such as spironolactone should only be prescribed in combination with safe contraception due to their risk of fetal undervirilisation. Additionally, substance specific risks should be considered. Baseline treatment of overweight or metabolic issues includes behaviour modification, weight reduction and physical activity. Additional benefit can be reached by combination of lifestyle changes with metformin. Studies indicate a positive effect of inositol and antidiabetic substances like liraglutide and empagliflozin but should be regarded as experimental therapies.

Acne is one of the most common skin diseases in the general population, especially among adolescents. Acne tarda (adult acne) is defined as acne that develops (late-onset acne) or continues (persistent acne) after 25 years of age. The disease is more common in women. The clinical features are quite specific: inflammatory acne in the lower facial region or macrocomedones (microcysts) spread over the face. Involvement of the trunk is much more common in men. The etiology of acne tarda is still controversial, as cosmetics, drugs, smoking, stress, diet, and endocrine abnormalities have been implicated. Women with acne tarda and other symptoms of hyperandrogenism have a high probability of endocrine abnormalities such as polycystic ovary syndrome. Treatment is similar to that of acne in adolescence. Long-term treatment over years or decades may be required.

An enhanced sebaceous gland activity with production of proinflammtory sebaceous lipids belongs to the major pathogenetic factors of acne. Hormonal antiandrogen treatment targets the androgen-metabolizing cells of the pilosebaceous unit, i. e. follicular kertinocytes and sebocytes, and leads to sebostasis, with a reduction of the sebum secretion rate of 12.5 to 65 %. Concerning their mechanism of action, hormonal antiandrogens are classified in androgen receptor blockers, inhibitors of circulating androgens by affecting the ovarial function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotrophin-releasing hormone agonists and dopamin agonists in hyperprolactinemia), inhibitors of the adrenal function, and inhibitors of peripheral androgen metabolism (5-reductase inhibitors, inhibitors of other enzymes).In this study, all original and review publications on hormonal antiandrogen treatment of acne as monotherapy or in combination included in MEDLINE, EMBASE and COCHRANE libraries were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog*" and "treatment" and classified according to their level of evidence.Antiandrogen treatment is overall active on acne lesions. The combinations of ethinyl estradiol with cyproterone acetate chlormadinone acetate, dienogest desogestrel and drospirenone have shown the strongest antiacne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotrophin-releasing hormone agonists and inhibitors of peripheral androgen metabolism are not recommended according to the current stand of knowledge. Low dose prednisolone is to only be administered at late onset congenital adrenal hyperplasia and dopamine agonists at hyperprolactinemia. Treatment with hormonal antiandrogens requires missing of any contraindications.Hormonal antiandrogen treatment is limited to female patients who present additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, females with acne tarda, persistent acne recalcitrant to treatment, with parallel wish of contraception, and as a requirement for a systemic isotretinoin treatment can be treated with hormonal antiandrogens. Hormonal antiandrogen treatment is not a primary monotherapy for uncomplicated acne.

A 27-year-old Caucasian (gravida 2 para 1) presented in week 16 of her twin pregnancy with worsening of hyperandrogenic symptoms. In week 17, she developed an acute abdomen due to a twisted, incarcerated right ovary, which was surgically removed. Histological analysis revealed a diffuse steroid cell hyperplasia. Postsurgery testosterone levels fell temporarily within normal limits, diminishing the hyperandrogenic symptoms. Over time androgen levels rose again slowly above normal values with clinical worsening of hirsutism. In the 32nd week of gestation, a cesarean section of two healthy female infants was necessary due to the development of preeclampsia. An ovarian biopsy revealed again the picture of hyperreactio luteinalis. Postpartum peripheral hormone levels fell within normal limits and the hyperandrogenic symptoms subsided.

Die dargestellte Klassifizierung des Funktionellen Hyperandrogenismus (FHA) basiert auf lange und seit jüngerer Zeit bekannten klinischen Erkenntnissen, die durch neuere molekularbiologische Vorstellungen untermauert werden. Man kann annehmen, dass sich der FHA aus verschiedenen, organ- oder systemspezifischen Entitäten zusammensetzt, die letztlich unterschiedliche Diagnostik- und Therapiestrategien zur Folge haben. Die Bezeichnung PCOS», welche die verschiedenen Entitäten ungenau und schieflastig umfasst, sollte durch die entsprechenden, adäquaten Begriffsbestimmungen ersetzt werden. Obwohl schon umfangreiche Denkansätze und Kenntnisse zu molekularbiologischen Abläufen beim FHA vorliegen, sind mit Ausnahme der hier nicht besprochenen FHA-Gruppe III (FAHA) die ätiologischen Folgerungen noch nicht gefestigt und die diagnostischen wie therapeutischen Konsequenzen weiterhin limitiert. Allerdings sind in der nahen Zukunft auf der Basis der jüngsten Erkenntnisse des menschlichen Genoms und den neuen genetischen screenings-Möglichkeiten (Microarrays) Weiterentwicklungen zu erwarten.

In approximately 30% of cases of chronic diffuse loss of scalp hair with a duration of at least 6 months, no underlying abnormality can be found. Typically this occurs in women, starting abruptly without a recognizable initiating factor, and involving the entire scalp area with increased shedding of telogen hair. With the exception of bitemporal recession, hair thinning is usually discrete, and contrasts to the great emotional overtones in this situation. This may initially lead to the differential diagnosis of psychogenic pseudo effluvium. Due to synchronization of the hair cycle, the amount of shed hair is greater than that in androgenetic alopecia, while miniaturized hairs are not a feature of the disorder. Overlap with androgenetic alopecia and/or psychogeneic pseudo effluvium is not uncommon. Scalp dysesthesia or a sensation of "pain in the hair" (trichodynia) is an accompanying symptom in a significant proportion of cases, and correlates better with emotional upset than with actual hair loss. Current therapeutic recommendations are pragmatic, and based on both experimental observations of the sheep wool industry and clinical experience. They include the use of L-cystine-containing oral preparations and of corticosteroids. Further investigation into the molecular controls of the hair cycle are required to find a more specific form of therapy, for which the expense and risk-benefit ratio seem appropriate for the treatment of this benign condition.

Family and personal history as well as clinical examination are the basic data to be known before laboratory examinations should be started. To obtain results that can be correctly interpreted, the blood sampling has to be done in the early morning hours between day 1 and 5 of the cycle, and for some hormones on an empty stomach. Depending on the clinical data, the hormonal screening can be selective and well directed, or it has to be broader. The presence or absence of galactorrhea, of hot flushes and of androgenization or virilization play an important role for the decision about the hormones to be determined. Furthermore, an eventual desire infertility will influence the selection of the hormonal tests to be done. The present review intends to propose some simple recommendations to the non-specialist how a gynaecological-endocrinological screening for the most important clinical questions should be organized.

Virilization in postmenopausal women is suspicious for androgen-secreting adrenal or ovarian tumors; however, iatrogenic androgenization needs to be additionally considered. Here we report on a 64-year-old patient who presented clinically with progressive signs of virilization. An adrenal source of androgen excess was excluded, and the patient strictly denied the use of any androgenic medication. Thus, elevated serum levels of testosterone were suspicious of ovarian hyperandrogenism. Shortly before planned surgical exploration, the clinical finding of an extensive vulvar lichen sclerosus pointed towards a possible long-term use of testosterone-containing cremes for symptomatic relief of this disease. Apparently, the patient did not consider the mere topical application of potent agents to be a medication. This case demonstrates that besides adrenal or ovarian sources of hyperandrogenism, iatrogenic androgenization has to be considered.