-
Clinical Endocrinology Aug 2022Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic... (Review)
Review
Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic ovary syndrome (PCOS), a common chronic condition that affects up to 10% of all women. Identification of women with non-PCOS pathology within large cohorts of patients presenting with androgen excess represents a diagnostic challenge for the endocrinologist, and rare pathology including nonclassic congenital adrenal hyperplasia, severe insulin resistance syndromes, Cushing's disease or androgen-secreting tumours of the ovary or adrenal gland may be missed in the absence of a pragmatic screening approach. Detailed clinical history, physical examination and biochemical phenotyping are critical in risk-stratifying women who are at the highest risk of non-PCOS disorders. Red flag features such as rapid onset symptoms, overt virilization, postmenopausal onset or severe biochemical disturbances should prompt investigations for underlying neoplastic pathology, including dynamic testing and imaging where appropriate. This review will outline a proposed diagnostic approach to androgen excess in women, including an introduction to androgen metabolism and provision of a suggested algorithmic strategy to identify non-PCOS pathology according to clinical and biochemical phenotype.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Virilism
PubMed: 35349173
DOI: 10.1111/cen.14710 -
Journal of the American Academy of... Jun 2019Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, and in other tissues, like the skin. Several androgens... (Review)
Review
Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, and in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone, dehydroepiandrosterone-sulfate, testosterone, dihydrotestosterone, and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL)-androgen-mediated cutaneous disorders (AMCDs). However, the role of androgens in the pathophysiology of these diseases is complicated and incompletely understood. In the first article in this Continuing Medical Education series, we discuss the role of the skin in androgen production and the impact of androgens on the skin in women. Specifically, we review the necessary but insufficient role that androgens play in the development of acne, hirsutism, and FPHL in women. Dermatologists face the challenge of differentiating physiologic from pathologic presentations of AMCDs in women. There are currently no dermatology guidelines outlining the indications for endocrinologic evaluation in women presenting with acne, hirsutism, or FPHL. We review the available evidence regarding when to consider an endocrinologic workup in women presenting with AMCDs, including the appropriate type and timing of testing.
Topics: Acne Vulgaris; Adrenal Gland Neoplasms; Adrenal Glands; Alopecia; Androgens; Cholesterol; Endocrinology; Female; Hair Follicle; Hirsutism; Humans; Menopause; Organ Specificity; Ovarian Neoplasms; Receptors, Androgen; Referral and Consultation; Scalp; Sebaceous Glands; Skin
PubMed: 30312644
DOI: 10.1016/j.jaad.2018.08.062 -
Clinical Chemistry Dec 2023Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the... (Review)
Review
BACKGROUND
Androgens are synthesized from cholesterol through sequential conversions by enzymes in the adrenal glands and gonads. Serum levels of androgens change during the different phases of life and regulate important developmental and maturational processes. Androgen excess or deficiency can therefore present at various ages in various ways.
CONTENT
The diagnostic approach for atypical genitalia, premature pubarche, delayed pubertal onset or progression, and hirsutism or virilization, including measurement of androgens (testosterone, androstenedione, 17-OHprogesterone, dehydroepiandrosterone, and dihydrotestosterone) is discussed in the current review. Androgens can be measured in serum, saliva, urine, or dried blood spots. Techniques to measure androgens, including immunoassays and LC-MS, have their own advantages and pitfalls. In addition, pre- and postanalytical issues are important when measuring androgens.
SUMMARY
During clinical interpretation of androgen measurements, it is important to take preanalytical circumstances, such as time of blood withdrawal, into account. As immunoassays have major drawbacks, especially in samples from women and neonates, concentrations measured using these assays should be interpreted with care. Reference intervals can only be used in relation to the measurement technique and the standardization of the assay. In the near future, new androgens will probably be added to the current repertoire to further improve the diagnosis and follow-up of androgen excess or deficiency.
Topics: Infant, Newborn; Female; Humans; Androgens; Testosterone; Androstenedione; Virilism; Hirsutism; Dehydroepiandrosterone
PubMed: 37794651
DOI: 10.1093/clinchem/hvad146 -
Current Opinion in Endocrinology,... Jun 2018To summarize recent data on the adverse reproductive consequences of androgen abuse, focusing on the recovery of reproductive function following androgen discontinuation. (Review)
Review
PURPOSE OF REVIEW
To summarize recent data on the adverse reproductive consequences of androgen abuse, focusing on the recovery of reproductive function following androgen discontinuation.
RECENT FINDINGS
Evidence is mostly based on case reports and observational studies. Androgen abuse leads to a state of hypogonadotropic hypogonadism associated with impaired spermatogenesis, testicular atrophy, gynecomastia as well as menstrual irregularities, virilization and subfertility. Recovery of the hypothalamic-pituitary-gonadal axis following androgen withdrawal depends on the type and characteristics of androgen administration (dose, duration of use) as well as those of the user (age, previous reproductive function). Biochemical and clinical features of hypogonadism may be evident months or even years following androgen discontinuation. To prevent androgen-related adverse effects and accelerate recovery of gonadal function, users take androgens in a cyclical fashion and use drugs such as human chorionic gonadotropin, antiestrogens and aromatase inhibitors, even though there is limited evidence to support efficacy of these strategies. As few studies refer to female androgen users, there is a lack of data concerning recovery from androgen-related reproductive side effects in women.
SUMMARY
Androgen abuse has profound and commonly under-recognized effects on the reproductive system; recovery following androgen withdrawal may be prolonged and occasionally incomplete.
Topics: Androgens; Chorionic Gonadotropin; Female; Humans; Hypogonadism; Infertility, Female; Infertility, Male; Male; Menstruation Disturbances; Reproduction; Spermatogenesis; Substance-Related Disorders; Testis; Virilism
PubMed: 29389675
DOI: 10.1097/MED.0000000000000406 -
Minerva Endocrinologica Mar 1995Virilizing adrenal tumours, adenomas and adenocarcinomas are rare and their clinical manifestations vary depending on age at onset. The paper reports the results... (Comparative Study)
Comparative Study Review
Virilizing adrenal tumours, adenomas and adenocarcinomas are rare and their clinical manifestations vary depending on age at onset. The paper reports the results obtained in 4 patients with adenoma and 3 with adenocarcinoma, as well as 11 cases of classic congenital adrenogenital syndrome by way of comparison. The hormonal status of adenomas is usually characterised by a predominant increase in plasma androstenedione (> 600, ng/dl) and testosterone (> 200 ng/dl), whereas carcinomas present a predominant hypersecretion of dehydroepiandrosterone (> 1200 ng/dl) and its sulphate (> 700 micrograms/dl). Plasma estrogen levels may also be enhanced due to active peripheral androgen conversion or direct secretion. 17alpha-hydroxyprogesterone, which is high in congenital adrenal hyperplasia, is normal or slightly enhanced, as is cortisol. Differential diagnosis must be made with androgen secreting tumours of the ovaries and, in males, with the various forms of precocious puberty, including endocrine tumours of the testicle, as well as congenital adrenogenital syndrome. A tumour with a diameter > 7 cm when examined using CT or NMR may be suspected as carcinoma, but malignancy cannot be excluded even in smaller tumours. Virilizing adrenal tumours do not usually respond to dexamethasone suppression test or ACTH stimulus since they do not express ACTH receptors or present post receptor anomalies. Steroidogenesis may be cAMP/protein-kinase independent and can be activated through alternative pathways. The presence of a stimulating G-protein has been detected in carcinomas which serves to activate adenylate cyclase on a permanent basis. b6 cytochrome is super-expressed and may be responsible for androgen over-secretion by activating 17,20-desmolase.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adenocarcinoma; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adult; Androgens; Child; Child, Preschool; Cushing Syndrome; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Retrospective Studies; Virilism
PubMed: 7651284
DOI: No ID Found -
The Journal of Clinical Endocrinology... Apr 2023Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other... (Review)
Review
Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment.
Topics: Female; Humans; Hyperandrogenism; Androgens; Diabetes Mellitus, Type 2; Postmenopause; Polycystic Ovary Syndrome; Virilism; Testosterone; Adrenal Gland Neoplasms
PubMed: 36409990
DOI: 10.1210/clinem/dgac673 -
Seminars in Oncology Dec 2010Androgen-secreting adrenal cancers are extremely rare malignancies, accounting for only a tiny proportion of the total number of women presenting with signs of androgen... (Review)
Review
Androgen-secreting adrenal cancers are extremely rare malignancies, accounting for only a tiny proportion of the total number of women presenting with signs of androgen excess. Estrogen-secreting adrenal cancers are rarer still. Understanding how these tumors work benefits from an appreciation of adrenal steroid biosynthesis, as it is said that secretion in cancers is an anarchic version of normal adrenal function. Selection of patients in whom we should have a high suspicion of a malignancy is vital, so that biochemical investigation and imaging is deployed appropriately. When an adrenal tumor is found to secrete androgens or estrogens to excess, it can be difficult to confirm that it is a cancer, as there is significant overlap in the secretory patterns and imaging appearances of benign and malignant disease. The most reliable indicator of malignancy in these tumors remains the presence of metastases. Treatment is essentially surgical, although the role of mitotane is one undergoing evaluation.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Adrenocortical Carcinoma; Adult; Algorithms; Androgens; Antineoplastic Agents, Hormonal; Child; Diagnostic Imaging; Estrogens; Female; Humans; Mitotane; Prognosis; Virilism
PubMed: 21167382
DOI: 10.1053/j.seminoncol.2010.10.016 -
Clinics in Dermatology 2006Hyperandrogenism in women can be caused by various conditions, the most prevalent of which is polycystic ovary syndrome. Common dermatologic manifestations of... (Review)
Review
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.
Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Androgens; Contraceptives, Oral; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Skin Diseases
PubMed: 16828411
DOI: 10.1016/j.clindermatol.2006.04.004 -
Seminars in Reproductive Medicine Aug 2002Disorders of androgen biosynthesis are a relatively rare cause of sexual ambiguity in 46,XY genetic males, but genetic disorders characterized by excessive androgen... (Review)
Review
Disorders of androgen biosynthesis are a relatively rare cause of sexual ambiguity in 46,XY genetic males, but genetic disorders characterized by excessive androgen synthesis are a common cause of virilization in 46,XX genetic females. Understanding of these disorders is relatively simple if one is familiar with the components of the various steroidogenic pathways. The biosynthesis of androgens requires the steroidogenic acute regulatory protein (StAR) and the steroidogenic enzymes P450scc, P450c17, 3betaHSDII, 17betaHSDIII, and 5alpha-reductase. Deficiencies have been described in all of these, leading to male pseudohermaphroditism. Other steroidogenic enzymes not involved in androgen biosynthesis, such as P450c21, P450c11beta, and P450aro, must also be considered, as mutations in these can result in overproduction of androgens, resulting in female pseudohermaphroditism.
Topics: Androgens; Disorders of Sex Development; Enzymes; Female; Humans; Male; Phosphoproteins; Steroids; Virilism
PubMed: 12428201
DOI: 10.1055/s-2002-35385 -
Frontiers of Hormone Research 2019Unwanted sexual hair growth has a considerable negative impact on a woman's self-esteem and quality of life. Excessive growth of terminal hair in women in a man-like... (Review)
Review
Unwanted sexual hair growth has a considerable negative impact on a woman's self-esteem and quality of life. Excessive growth of terminal hair in women in a man-like pattern is defined as hirsutism and affects up to 1 in 7 women. Androgens secreted by the ovary and adrenal are the main regulator of physiological and pathological alterations of skin hair. Hirsutism is the result of the interaction between circulating serum androgens and hair follicles. Hirsutism is the most commonly used clinical diagnostic criterion of hyperandrogenism and majority of hirsutism cases are due to androgen excess. Over 80% of women with hirsutism will have polycystic ovary syndrome, about 10% will have idiopathic hirsutism, and the remaining will have rare disorders including non-classical congenital adrenal hyperplasia, hyperandrogenism with insulin resistance and acanthosis nigricans, and androgen-secreting neoplasms. Cushing's syndrome, acromegaly, thyroid dysfunction and hyperprolactinemia might be associated with hirsutism as well as the use of androgens, anabolic steroids and valproate. This paper provides an overview of the principal endocrinological aspects of hirsutism including the role of androgens in excessive hair growth and associated androgen excess disorders. Clinical evaluation and management of hirsutism are also discussed.
Topics: Androgens; Female; Hirsutism; Humans; Hyperandrogenism
PubMed: 31499500
DOI: 10.1159/000494907