-
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 -
Dermatology (Basel, Switzerland) 2023Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long... (Review)
Review
Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long been thought to be driven by genetic and androgen predisposition. However, increasingly, data proposed ageing and AGA are intimately linked. Elevated senescent cell burden and androgen and oxidative stress-induced senescence mechanisms in ageing may be initial targets to improve AGA. This review summarizes the biological links between ageing and AGA, with special focus on cellular senescence. In addition, we discuss the potential therapeutic strategies for improving cellular senescence in AGA, such as inhibiting dermal papilla cells and hair follicle stem cells senescence driven by androgen and reactive oxygen species, removing senescent cell, and reducing senescence-associated secretory phenotype (SASP).
Topics: Humans; Androgens; Alopecia; Hair Follicle; Cellular Senescence; Oxidative Stress
PubMed: 37088073
DOI: 10.1159/000530681 -
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 -
Molecular and Cellular Endocrinology Apr 2018The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which... (Review)
Review
The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits.
Topics: Androgens; Animals; Humans; Models, Biological; Organ Specificity; Receptors, Androgen
PubMed: 28624515
DOI: 10.1016/j.mce.2017.06.013 -
The Journal of Clinical Endocrinology... Jul 2019The lifetime prevalence of anabolic androgenic steroid (AAS) use is estimated at 1% to 5% worldwide. AAS use occurs primarily male elite athletes and men who want a... (Review)
Review
CONTEXT
The lifetime prevalence of anabolic androgenic steroid (AAS) use is estimated at 1% to 5% worldwide. AAS use occurs primarily male elite athletes and men who want a muscular appearance. The evidence for effective, safe management of AAS cessation and withdrawal is weak.
DESIGN
Key studies were extracted from PubMed (1990-2018) and Google Scholar with reference searches from relevant retrieved articles.
RESULTS
The proven adverse effects of AASs include suppression of the gonadal axis and infertility, hirsutism and defeminization in women, and erythrocytosis. Alkylated AASs that are taken orally may cause hepatopathy. There is an association between high-dosage AAS use and increased risk of cardiovascular disease. Clues for AAS use include very low serum high-density cholesterol and sex hormone-binding globulin concentrations and unexplained erythrocytosis. For elite athletes, the biological passport (monitoring of blood or urinary androgen and androgen precursor concentrations after determining the athlete's baseline) is useful for detecting AAS use. For nonelite athletes, the best method to confirm AAS use is to inquire in a nonjudgmental manner. Cessation of chronic AAS use is associated with a withdrawal syndrome of anxiety and depression.
CONCLUSIONS
Men who use AASs <1 year typically recover normal hypothalamic-pituitary-testicular axis function within 1 year after cessation. Men who have infertility due to high-dosage AAS use ≥1 year might benefit from short-term treatment with clomiphene or human chorionic gonadotropin.
Topics: Anabolic Agents; Androgens; Athletes; Doping in Sports; Dose-Response Relationship, Drug; Female; Humans; Male; Performance-Enhancing Substances; Prevalence; Sex Factors; Substance Abuse Detection; Substance-Related Disorders
PubMed: 30753550
DOI: 10.1210/jc.2018-01882 -
Current Opinion in Endocrinology,... Dec 2021The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use.
RECENT FINDINGS
Supraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems.
SUMMARY
Findings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.
Topics: Aging; Androgens; Animals; Brain; Cognition; Humans; Testosterone
PubMed: 34709215
DOI: 10.1097/MED.0000000000000675 -
Journal of Ayub Medical College,... 2021One of the leading causes of infertility in child bearing age females is polycystic ovary syndrome. It is characterized by altered hormonal profile causing androgen...
BACKGROUND
One of the leading causes of infertility in child bearing age females is polycystic ovary syndrome. It is characterized by altered hormonal profile causing androgen excess and insulin resistance which eventually leads to decreased ovulation rate.
METHODS
This was a crosssectional study that included 40 polycystic ovary syndrome (PCOS) patients and 40 infertility patients that did not have polycystic ovary syndrome determined by sonography and clinical features through quota sampling technique. Serum Total Testosterone and Sex Hormone Binding Globulin Levels were assayed. Using these two parameters, Free Androgen Index was calculated. Body Mass Index and central obesity was also determined.
RESULTS
Total Testosterone, Free Androgen Index and Body Mass Index were raised in PCOS group as indicated by p-value <0.05. Hirsutism was present in PCOS group (p-value <0.05). Sex Hormone Binding Globulin Levels were decreased in PCOS patients (p-value <0.05) but were within the lower half of normal range.
CONCLUSIONS
Levels of Sex Hormone Binding Globulin were decreased in PCOS cases and Free Androgen Index can help in better determining hyperandrogenaemia than total testosterone alone.
Topics: Androgens; Body Mass Index; Female; Hirsutism; Humans; Hyperandrogenism; Infertility; Polycystic Ovary Syndrome; Testosterone
PubMed: 35124911
DOI: No ID Found -
Molecular and Cellular Endocrinology Apr 2018Androgens play an important role in metabolic homeostasis and reproductive health in both men and women. Androgen signalling is dependent on androgen receptor... (Review)
Review
Androgens play an important role in metabolic homeostasis and reproductive health in both men and women. Androgen signalling is dependent on androgen receptor activation, mostly by testosterone and 5α-dihydrotestosterone. However, the intracellular or intracrine activation of C androgen precursors to active androgens in peripheral target tissues of androgen action is of equal importance. Intracrine androgen synthesis is often not reflected by circulating androgens but rather by androgen metabolites and conjugates. In this review we provide an overview of human C steroid biosynthesis including the production of 11-oxygenated androgens, their transport in circulation and uptake into peripheral tissues. We conceptualise the mechanisms of intracrinology and review the intracrine pathways of activation and inactivation in selected human tissues. The contribution of liver and kidney as organs driving androgen inactivation and renal excretion are also highlighted. Finally, the importance of quantifying androgen metabolites and conjugates to assess intracrine androgen production is discussed.
Topics: Androgens; Animals; Biosynthetic Pathways; Humans; Organ Specificity; Reproduction; Steroids
PubMed: 28865807
DOI: 10.1016/j.mce.2017.08.016 -
Clinica Chimica Acta; International... Jun 2022Hirsutism is the excessive growth of terminal hair in a male pattern in a female. In most hirsute women, hirsutism is caused by increased androgens. However, not all... (Review)
Review
BACKGROUND
Hirsutism is the excessive growth of terminal hair in a male pattern in a female. In most hirsute women, hirsutism is caused by increased androgens. However, not all women with hirsutism actually show elevated levels of circulating androgens with standard laboratory tests, in which case we speak of idiopathic hirsutism (IH).
OBJECTIVES
The aim of this paper is to investigate whether there are biochemical markers that can be used to unravel the cause in IH.
METHODS
An electronic search through the PubMed database was conducted to find studies describing potential biomarkers for IH.
RESULTS
The majority of included studies claimed an increased 5α-reductase (5α-RD) activity in women with IH by means of increased DHT metabolite levels. Studies investigating abnormalities of the androgen receptor (AR) and serum levels of indirect markers showed no significant differences.
CONCLUSIONS
Our literature search showed that polymorphisms of the AR as well as indirect markers seem to be nonspecific, but that the dihydrotestosterone-reduced metabolite 5α-androstane-3α,17β-diol glucuronide is markedly enhanced in women with IH, suggesting an increased 5α-RD activity in these women. Further studies need to be performed to determine the clinical usefulness of 3α-diol G as a biomarker for IH.
Topics: Androgens; Androstane-3,17-diol; Dihydrotestosterone; Female; Hirsutism; Humans; Testosterone
PubMed: 35292252
DOI: 10.1016/j.cca.2022.03.011 -
Current Opinion in Endocrinology,... Jun 2018To summarize recent findings regarding the public health impact of androgen abuse. (Review)
Review
PURPOSE OF REVIEW
To summarize recent findings regarding the public health impact of androgen abuse.
RECENT FINDINGS
Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease. Withdrawal from androgens after long-term use may produce prolonged and sometimes irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes cause irritability, aggressiveness, and violence, whereas androgen withdrawal may cause depression. However, these psychiatric effects are idiosyncratic, affecting only a minority of users. Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia. Several recent studies have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse musculoskeletal effects.
SUMMARY
Recent studies have demonstrated marked adverse effects of long-term androgen abuse. As increasing numbers of androgen abusers reach middle age, these effects will likely represent an emerging public health problem.
Topics: Anabolic Agents; Androgens; Cardiovascular Diseases; Humans; Hypogonadism; Male; Mental Disorders; Middle Aged; Neurosecretory Systems; Public Health; Substance-Related Disorders
PubMed: 29369918
DOI: 10.1097/MED.0000000000000404