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The Journal of Gender-specific Medicine... 2000Hormones play an important role in cutaneous physiology. The androgen hormones are of particular relevance in modulating hair growth and sebum production in the... (Review)
Review
Hormones play an important role in cutaneous physiology. The androgen hormones are of particular relevance in modulating hair growth and sebum production in the pilosebaceous unit, which is comprised of the hair follicle and sebaceous gland. Testosterone arising from the circulation is converted peripherally to its more potent, reduced form, dihydrotestosterone, by the enzyme 5 alpha-reductase. Dihydrotestosterone is primarily responsible for androgen receptor binding and exerting end-organ effects. The clinical sequelae of enhanced local androgen production include androgenetic alopecia, hirsutism, and acne. These disorders can be fraught with significant psychosocial ramifications because of their highly visible nature and impact on perceptions of masculinity and femininity.
Topics: Acne Vulgaris; Androgens; Female; Hair Follicle; Hirsutism; Humans; Male; Sebaceous Glands
PubMed: 11253232
DOI: No ID Found -
The Journal of Reproductive Medicine Mar 2001A persistent view of testosterone as the "male hormone" deprives many clinically androgen deficient women of effective treatment, although data from the 1960s to the... (Review)
Review
A persistent view of testosterone as the "male hormone" deprives many clinically androgen deficient women of effective treatment, although data from the 1960s to the present have indicted the importance of androgens to libido and feelings of well-being in women, providing relief from vasomotor symptoms that are unresponsive to estrogen alone. The safety of androgen replacement therapy is reviewed in this article. The risk of androgen toxicity is influenced by dosage and route of administration. Most products developed for use in men produce androgen levels that are too high for safety in women. Low-dose androgen replacement therapy as used in women, 1.25 mg esterified estrogen (EE) + 2.5 mg methyltestosterone (MT), or a half-strength preparation, 0.625 mg EE plus 1.25 mg MT, is unlikely to produce commonly described side effects: liver dysfunction, adverse lipid effects or virilization, as reviewed in this article. The potential for adverse endometrial effects if used by women with uteri unless a progestogen is used is also discussed. Low-dose estrogen/androgen therapy offers beneficial cardiovascular effects, primarily regarding lipids, atherogenesis and vasodilation. Androgens may act independently on the cardiovascular system and may be mediated by estrogen metabolites (aromatization products) or by secondary effects of androgens on estrogen bioavailability and metabolism (sex hormone binding globulin [SHBG] effects). They may improve vasomotor stability and reduce triglyceride (TG) levels. The marked reduction in TG in the estrogen/androgen (E/A) regimen is of note because women who experience oophorectomy have significantly increased levels of TG as compared with women who are naturally menopausal. Androgens offer positive effects on bone. Various types of studies--including cell culture, preclinical and observational--have attempted to document potential associations between androgens and breast cancer. Androgen administration has been shown to induce down-regulation of mammary epithelial proliferation and estrogen receptor expression, suggesting that E/A therapy might reduce the risk of breast cancer associated with ERT. However, studies of the relation of breast cancer to elevated circulating androgen levels have yielded inconsistent results. Testosterone may have an indirect effect on breast cancer risk because of its association with estrogen levels. Testosterone's effect on estrogen bioavailability may be of importance since an increase in serum testosterone levels could lead to a decrease in the percent of estradiol bound to SHBG. For the surgically menopausal woman faced with significant symptoms and health risks associated with estrogen withdrawal, E/A supplementation offers a reasonable course of treatment.
Topics: Androgens; Breast Neoplasms; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Estrogen Replacement Therapy; Estrogens; Female; Hormone Replacement Therapy; Humans; Middle Aged; Postmenopause; Testosterone; Virilism
PubMed: 11304876
DOI: No ID Found -
Annals of Allergy, Asthma & Immunology... Apr 2015To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE). (Review)
Review
OBJECTIVE
To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE).
DATA SOURCES
PubMed was searched with no time limitations using the keywords hereditary angioedema or angio-oedema combined with danazol, stanozolol, and androgen.
STUDY SELECTION
Qualifying articles were English-language reports of androgen use in patients with HAE, with relevant safety and/or efficacy information. Reports were categorized according to level of evidence (LOE).
RESULTS
The search process identified 153 citations, 63 of which contained relevant information; 2 additional publications were identified while other citations were being reviewed. Fifteen LOE 2 studies and multiple LOE 4 reports provided efficacy data, confirming a high level of prophylactic efficacy for androgen therapy in HAE, with occasional reports of poor prophylactic response. Common adverse events include weight gain, menstrual irregularities, virilization, headaches, myalgias or cramps, mood changes, and elevations in creatine phosphokinase level, liver function test results, and serum lipid level. The risk of adverse events is often correlated with dose and/or treatment duration. Rare cases of hepatic adenomas and hepatocellular carcinoma associated with long-term androgen use often had no preceding changes in liver function test results.
CONCLUSION
Androgen therapy may be effective for most patients with HAE; however, potential risks and adverse effects must be carefully considered and discussed with patients when considering options for long-term HAE prophylaxis.
Topics: Androgens; Angioedemas, Hereditary; Animals; Danazol; Drug Dosage Calculations; Female; Humans; Lipid Metabolism; Menstruation Disturbances; Obesity; Risk Assessment; Stanozolol; Time Factors; Virilism
PubMed: 25707325
DOI: 10.1016/j.anai.2015.01.003 -
The Journal of Endocrinology Sep 2023Since the discovery in 1968 that dihydrotestosterone (DHT) is a major mediator of androgen action, a convincing body of evidence has accumulated to indicate that the...
Since the discovery in 1968 that dihydrotestosterone (DHT) is a major mediator of androgen action, a convincing body of evidence has accumulated to indicate that the major pathway of DHT formation is the 5α-reduction of circulating testosterone in androgen target tissues. However, we now know that DHT can also be formed in peripheral tissues by the oxidation of 5α-androstane-3α,17β-diol (adiol). This pathway is responsible for the formation of the male phenotype. We discuss the serendipitous discovery in the tammar wallaby of an alternate pathway by which adiol is formed in the testes, secreted into plasma and converted in peripheral tissues to DHT. This alternate pathway is responsible for virilisation of the urogenital system in this species and is present in the testes at the onset of male puberty of all mammals studied so far. This is the first clear-cut function for steroid 5α-reductase 1 in males. Unexpectedly, the discovery of this pathway in this Australian marsupial has had a major impact in understanding the pathophysiology of aberrant virilisation in female newborns. Overactivity of the alternate pathway appears to explain virilisation in congenital adrenal hyperplasia CAH, in X-linked 46,XY disorders of sex development. It also appears to be important in polycystic ovarian syndrome (PCOS) since PCOS ovaries have enhanced the expression of genes and proteins of the alternate pathway. It is now clear that normal male development in marsupials, rodents and humans requires the action of both the classic and the alternate (backdoor) pathways.
Topics: Infant, Newborn; Humans; Animals; Male; Female; Androgens; Australia; Testosterone; Dihydrotestosterone; Macropodidae; Virilism
PubMed: 37343228
DOI: 10.1530/JOE-22-0296 -
Metabolism: Clinical and Experimental Jul 1972
Review
Topics: 17-Ketosteroids; Adrenal Glands; Adrenal Hyperplasia, Congenital; Androgens; Androstanes; Androstenols; Blood Proteins; Electrophoresis, Starch Gel; Female; Hirsutism; Humans; Hypertrichosis; Leydig Cell Tumor; Liver; Metabolic Clearance Rate; Ovarian Cysts; Ovarian Neoplasms; Ovary; Testosterone; Virilism
PubMed: 4562220
DOI: 10.1016/0026-0495(72)90090-x -
Clinical Endocrinology Aug 2011Evidence of clinical and/or biochemical androgen excess connotes a unique differential diagnosis in postmenopausal women. Providers need to be able to discriminate... (Review)
Review
Evidence of clinical and/or biochemical androgen excess connotes a unique differential diagnosis in postmenopausal women. Providers need to be able to discriminate between changes of the normal ageing process compared to potential pathology in older women. The evaluation and treatment of postmenopausal hirsutism and hyperandrogenism is reviewed. Androgen excess may have long-term negative health consequences and as such should be detected and treated.
Topics: Androgens; Diagnosis, Differential; Female; Hirsutism; Humans; Hyperandrogenism; Postmenopause
PubMed: 21521309
DOI: 10.1111/j.1365-2265.2011.04040.x -
Cleveland Clinic Journal of Medicine 1990The most common signs of androgen excess in women are acne, alopecia, and hirsutism. Less common manifestations include android obesity, virilization, and acanthosis... (Review)
Review
The most common signs of androgen excess in women are acne, alopecia, and hirsutism. Less common manifestations include android obesity, virilization, and acanthosis nigricans. These changes appear to be the result of excessive androgen production or increased target organ sensitivity. To evaluate excessive androgen production, an androgen screening protocol is recommended that includes measurement of dehydroepiandrosterone sulfate, testosterone, androstenedione, prolactin, follicular stimulating hormone, and luteinizing hormone. When androgen excess is confirmed, dexamethasone suppression is recommended to determine the source of the androgen(s). Once excessive androgen production is confirmed, more specific therapies can be administered.
Topics: Acne Vulgaris; Alopecia; Androgens; Clinical Protocols; Endocrine System Diseases; Female; Hirsutism; Humans
PubMed: 2142637
DOI: 10.3949/ccjm.57.5.423 -
Proceedings of the National Academy of... Oct 2019Androgen biosynthesis in the human fetus proceeds through the adrenal sex steroid precursor dehydroepiandrosterone, which is converted to testosterone in the gonads,...
Androgen biosynthesis in the human fetus proceeds through the adrenal sex steroid precursor dehydroepiandrosterone, which is converted to testosterone in the gonads, followed by further activation to 5α-dihydrotestosterone in genital skin, thereby facilitating male external genital differentiation. Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency results in disrupted dehydroepiandrosterone biosynthesis, explaining undervirilization in affected boys. However, many affected girls are born virilized, despite low circulating androgens. We hypothesized that this is due to a prenatally active, alternative androgen biosynthesis pathway from 17α-hydroxyprogesterone to 5α-dihydrotestosterone, which bypasses dehydroepiandrosterone and testosterone, with increased activity in congenital adrenal hyperplasia variants associated with 17α-hydroxyprogesterone accumulation. Here we employ explant cultures of human fetal organs (adrenals, gonads, genital skin) from the major period of sexual differentiation and show that alternative pathway androgen biosynthesis is active in the fetus, as assessed by liquid chromatography-tandem mass spectrometry. We found androgen receptor expression in male and female genital skin using immunohistochemistry and demonstrated that both 5α-dihydrotestosterone and adrenal explant culture supernatant induce nuclear translocation of the androgen receptor in female genital skin primary cultures. Analyzing urinary steroid excretion by gas chromatography-mass spectrometry, we show that neonates with P450 oxidoreductase deficiency produce androgens through the alternative androgen pathway during the first weeks of life. We provide quantitative in vitro evidence that the corresponding P450 oxidoreductase mutations predominantly support alternative pathway androgen biosynthesis. These results indicate a key role of alternative pathway androgen biosynthesis in the prenatal virilization of girls affected by congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Glands; Androgens; Antley-Bixler Syndrome Phenotype; Cells, Cultured; Female; Fetus; Genitalia; Gonads; Humans; Male; Receptors, Androgen; Sex Differentiation; Virilism
PubMed: 31611378
DOI: 10.1073/pnas.1906623116 -
Gynecological Endocrinology : the... Dec 2022The purpose of the study was to investigate the biochemical and metabolic abnormalities related to the cutaneous characteristics of PCOS.
AIM
The purpose of the study was to investigate the biochemical and metabolic abnormalities related to the cutaneous characteristics of PCOS.
MATERIAL–METHODS
Patients diagnosed with PCOS were included in the study. Demographic data and accompanying androgen-dependent skin findings (acne, seborrhea, androgenic alopecia, acanthosis nigricans, skin tag, and hirsutism) were recorded. The free testosterone, total testosterone, dehydroepiandrosterone sulfate, androstenedione,17-Hidroksi progesterone, sex hormone binding globulin, prolactin, fasting glucose, fasting insulin, HbA1C, HDL, and triglycerides, follicle-stimulating hormone, luteinized hormone, free androgen index, and HOMA-IR levels of the patients were measured. The hormonal values of the patients with PCOS with and without skin findings were compared.
RESULTS
The HOMA-IR values of the acanthosis nigricans (+) PCOS group were significantly higher than the acanthosis nigricans (-) PCOS group ( < .001). The DHEA-SO4, FAI, and FI values of patients with hirsutism (HR) (+) PCOS were found to be statistically higher than patients with HR (-) PCOS ( = .006, = .015, = .004).
CONCLUSION
PCOS is among the most common endocrine disorders of women of reproductive age and was associated with some hormonal, metabolic, and skin findings. Certain androgenic and metabolic variables developing in PCOS might correlate with cutaneous symptoms.
Topics: Female; Humans; Polycystic Ovary Syndrome; Androgens; Hirsutism; Acanthosis Nigricans; Testosterone
PubMed: 36579834
DOI: 10.1080/09513590.2022.2162496 -
Cleveland Clinic Journal of Medicine May 1990Advances in technology, such as saturation analysis and nonisotopic immunoassays, have improved the measurement of androgens, binding proteins, and hormone receptors,... (Review)
Review
Advances in technology, such as saturation analysis and nonisotopic immunoassays, have improved the measurement of androgens, binding proteins, and hormone receptors, and clarified the diagnosis of idiopathic hirsutism. Immunoassay methods in steroid biochemistry enable accurate measurement of low concentrations of various androgens and their metabolites; and high-specificity antisera with chemical blocking agents allow measurement of these steroid directly in plasma without resorting to extraction methods. The future may bring the capacity to measure free concentrations.
Topics: Alopecia; Androgens; Female; Hirsutism; Humans; Radioimmunoassay
PubMed: 2192818
DOI: 10.3949/ccjm.57.3.292