Hyperandrogenism is a group of endocrinopathies characterized by excessive secretion or high activity of male sex hormones in the female body. Manifestations of various syndromes, similar in symptoms, but different in pathogenesis, are disorders of metabolic, menstrual and reproductive functions, androgenic dermopathy (seborrhea, acne, hirsutism, alopecia). The diagnosis of hyperandrogenism in women is based on examination data, hormonal screening, ultrasound of the ovaries, CT of the adrenal glands and pituitary gland. Correction of hyperandrogenism in women is carried out with the help of COCs or corticosteroids, tumors are removed promptly.
Hyperandrogenism is a concept that combines pathogenetically heterogeneous syndromes caused by increased production of androgens by the endocrine system or excessive susceptibility of target tissues to them. The significance of hyperandrogenism in the structure of gynecological pathology is explained by its wide spread among women of childbearing age (4-7.5% in adolescent girls, 10-20% in patients older than 25 years).
Androgens – male sex hormones of the steroid group (testosterone, ASD, DHEA-C, DHT) are synthesized in a woman’s body by the ovaries and adrenal cortex, less by subcutaneous fat under the control of pituitary hormones (ACTH and LH). Androgens act as precursors of glucocorticoids, female sex hormones – estrogens and form libido. At puberty, androgens are the most significant in the process of growth spurt, maturation of tubular bones, closure of diaphyseal-epiphyseal cartilage zones, the appearance of female-type hair loss. However, an excess of androgens in the female body causes a cascade of pathological processes that violate general and reproductive health.
Hyperandrogenism in women not only causes the occurrence of cosmetic defects (seborrhea, acne, alopecia, hirsutism, virilization), but also causes disorders of metabolic processes (fat and carbohydrate metabolism), menstrual and reproductive function (folliculogenesis abnormalities, polycystic ovarian degeneration, progesterone deficiency, oligomenorrhea, anovulation, miscarriage, female infertility). Prolonged hyperandrogenism in combination with dysmetabolism increases the risk of endometrial hyperplasia and cervical cancer, type II diabetes mellitus and cardiovascular pathology in women.
In gynecology, hyperandrogenism of ovarian (ovarian), adrenal (adrenal) and mixed genesis is differentiated. Hyperandrogenism in women can be primary and secondary (with violation of pituitary regulation), be hereditary and acquired. Hyperandrogenism can be absolute (with an increase in the level of androgens in the blood), but more often relative (with a normal amount of androgens, but their increased metabolism into more active forms or with increased utilization in overly susceptible target organs – ovaries, skin, sebaceous, sweat glands and hair follicles).
Hyperandrogenism with excessive androgen synthesis in women in most cases is determined by polycystic ovary syndrome: primary (Stein-Leventhal syndrome) and secondary (against the background of neuroendocrine hypothalamic syndrome, hyperprolactinemia, hypothyroidism), as well as adrenogenital syndrome (AHS, congenital adrenal hyperplasia). In AGS, the increased production of androgens is due to a deficiency of the enzyme 21-hydroxylase and a high level of ACTH. An excess of prolactin (galactorrhea-amenorrhea syndrome) can act as a stimulator of androgen synthesis. The causes of hyperandrogenism include the presence of virilizing ovarian tumors (luteomas, tecomas) and adrenal glands (androsteromas), stromal ovarian tecomatosis.
The development of the transport form of hyperandrogenism in women is noted against the background of insufficiency of globulin binding sex steroids (GBSS), blocking the activity of the free fraction of testosterone (with Itsenko-Cushing syndrome, hypothyroidism, dyslipoproteidemia). Compensatory hyperinsulism in pathological insulin resistance of target cells contributes to increased activation of androgen-secreting cells of the ovarian-adrenal complex.
In 70-85% of women with acne, hyperandrogenism is observed with normal indicators of androgens in the blood and hypersensitivity of the sebaceous glands to them due to an increase in the density of hormonal receptors of the skin. The main regulator of proliferation and lipogenesis in the sebaceous glands – dihydrotestosterone (DHT) – stimulates hypersecretion and changes in the physico–chemical properties of sebum, leading to the closure of the excretory ducts of the sebaceous glands, the formation of comedones, the appearance of acne and acne.
Hirsutism is associated with androgen hypersecretion in 40-80% of cases, in the rest – with the increased conversion of testosterone into more active DHT, provoking excessive growth of core hair in androgen-sensitive areas of the female body or hair loss on the head. In addition, women may have iatrogenic hyperandrogenism caused by taking medications with androgenic activity.
The clinic of hyperandrogenism in women depends on the severity of the disorders. With hyperandrogenism of non-tumor genesis, for example, with PCOS, clinical signs slowly progress over several years. The initial symptoms manifest during puberty, clinically manifested by oily seborrhea, vulgar acne, menstrual cycle disorders (irregularity, alternation of delays and oligomenorrhea, in severe cases – amenorrhea), excessive hair loss of the face, arms, legs. Subsequently, cystic transformation of the ovarian structure develops, anovulation, progesterone deficiency, relative hyperestrogenemia, endometrial hyperplasia, decreased fertility and infertility. In postmenopause, hair loss is noted first in the temporal regions (bitemporal alopecia), then in the parietal region (parietal alopecia). Pronounced androgenic dermatopathy in many women leads to the development of neurotic and depressive states.
Hyperandrogenism in AHS is characterized by virilization of the genitals (female pseudohermaphroditism), masculinization, late menarche, breast underdevelopment, coarsening of the voice, hirsutism, acne. Severe hyperandrogenism with impaired pituitary function is accompanied by a high degree of virilization, massive android-type obesity. The high activity of androgens contributes to the development of metabolic syndrome (hyperlipoproteinemia, insulin resistance, type II diabetes), hypertension, atherosclerosis, coronary heart disease. With androgen-secreting tumors of the adrenal glands and ovaries, symptoms develop rapidly and progress rapidly.
In order to diagnose pathology, a thorough anamnesis and physical examination is carried out with an assessment of sexual development, the nature of menstrual disorders and hair loss, signs of dermopathy; total and free testosterone, DHT, DEA-C, GBSS in blood serum are determined. Detection of an excess of androgens requires clarification of its nature – adrenal or ovarian.
The marker of adrenal hyperandrogenism is an increased level of DHEA-C, and ovarian hyperandrogenism is an increase in the amount of testosterone and ASD. With a very high level of DHEA-C >800 mcg /dl or total testosterone >200 ng / dl, women suspect an androgen-synthesizing tumor, which requires CT or MRI of the adrenal glands, ultrasound of the pelvic organs, with the difficulty of visualizing the neoplasm – selective catheterization of the adrenal and ovarian veins. Ultrasound diagnostics also allows to establish the presence of polycystic ovarian deformity.
In ovarian hyperandrogenism, the hormonal background of a woman is evaluated: prolactin, LH, FSH, estradiol levels in the blood; in adrenal – 17-OPG in the blood, 17-CS and cortisol in the urine. It is possible to conduct functional tests with ACTH, tests with dexamethasone and HCG, performing a pituitary CT. It is mandatory to study carbohydrate and fat metabolism (glucose, insulin, HbA1c levels, total cholesterol and its fractions, glucose-tolerant test). Women with hyperandrogenism are advised by an endocrinologist, dermatologist, and geneticist.
Treatment of hyperandrogenism is long-term, requiring a differentiated approach to the management tactics of patients. The main means of correcting hyperandrogenic conditions in women are estrogen-gestagenic oral contraceptives with an antiandrogenic effect. They provide inhibition of the production of gonadotropins and the ovulation process, suppression of the secretion of ovarian hormones, including testosterone, an increase in the level of GBSS, blocking of androgen receptors. Hyperandrogenism in AGS is stopped with corticosteroids, they are also used to prepare a woman for pregnancy and during gestation with this type of pathology. In the case of high hyperandrogenism, courses of antiandrogenic drugs in women are extended to a year or more.
Peripheral blockade of androgen receptors is clinically effective in androgen-dependent dermatopathy. At the same time, pathogenetic treatment of subclinical hypothyroidism, hyperprolactinemia, and other disorders is carried out. Insulin sensitizers (metformin), weight loss measures (hypocaloric diet, physical activity) are used to treat women with hyperinsulism and obesity. Against the background of the ongoing treatment, the dynamics of laboratory and clinical indicators are monitored.
Androgen-secreting tumors of the ovaries and adrenal glands are usually benign in nature, but when they are detected, surgical removal is mandatory. Relapses are unlikely. With hyperandrogenism, dispensary supervision and medical support of a woman for successful pregnancy planning in the future are indicated.