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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 -
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 -
Reproductive Sciences (Thousand Oaks,... Nov 2022PCOS or polycystic ovary syndrome is a common endocrine disorder that occurs during the reproductive age in females. It manifests in the form of a wide range of symptoms... (Review)
Review
PCOS or polycystic ovary syndrome is a common endocrine disorder that occurs during the reproductive age in females. It manifests in the form of a wide range of symptoms including (but not limited to) hirsutism, amenorrhea, oligomenorrhea, obesity, acne vulgaris, infertility, alopecia, and insulin resistance. The incidence of depression in PCOS population is increasing as compared to the general population. Increased depression in PCOS significantly alters the quality of life (QOL) of affected females. Also, self-esteem is found to be low in both depression and PCOS. The loss in self-esteem in such patients can be largely attributed to the associated factors including (but not limited to) obesity, acne, androgenic alopecia, and hirsutism. The reason behind the occurrence of depression in PCOS remains elusive to date. Literature suggests that there is an overlap of clinical symptoms between depression and PCOS. As the symptoms overlap, there is a possibility of common associations between depression, PCOS, and PCOS-associated abnormalities including insulin resistance (IR), obesity, CVD, and androgen excess. Studies demonstrate that depression is an inflammatory disorder marked with increased levels of inflammatory markers. On the other hand, PCOS is also regarded as a pro-inflammatory state that is characterized by increased levels of pro-inflammatory markers. Thus, there is a possibility of an inflammatory relationship existing between depression and PCOS. It is also possible that the inflammatory markers in PCOS can cross the blood-brain barrier (BBB) leading to the development of depression. Through the present review, we have attempted to shed light on common associations/shared links between depression and PCOS with respect to the levels of cortisol, androgen, vitamin D, neurotransmitters, monoaminoxidase (MAO), and insulin-like growth factor-1 (IGF-1). Tracking down common associations between depression and PCOS will help find potential drug therapies and improve the QOL of females with depression in PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Quality of Life; Insulin Resistance; Androgens; Depression; Acne Vulgaris; Obesity; Alopecia
PubMed: 34642910
DOI: 10.1007/s43032-021-00765-2 -
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 -
Endocrine Practice : Official Journal... Nov 2015Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the...
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.
Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism, alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty. Menstrual irregularities with anovulatory cycles and varied cycle length are common due to the immaturity of the hypothalamic-pituitary-ovarian axis in the 2- to 3-year time period post-menarche. Persistent oligomenorrhea 2 to 3 years beyond menarche predicts ongoing menstrual irregularities and greater likelihood of underlying ovarian or adrenal dysfunction. In adolescent girls, large, multicystic ovaries are a common finding, so ultrasound is not a first-line investigation in women <17 years of age. Ovarian dysfunction in adolescents should be based on oligomenorrhea and/or biochemical evidence of oligo/anovulation, but there are major limitations to the sensitivity of T assays in ranges applicable to young girls. Metformin is commonly used in young girls and adolescents with PCOS as first-line monotherapy or in combination with OCPs and anti-androgen medications. In lean adolescent girls, a dose as low as 850 mg daily may be effective at reducing PCOS symptoms; in overweight and obese adolescents, dose escalation to 1.5 to 2.5 g daily is likely required. Anti-androgen therapy in adolescents could affect bone mass, although available short-term data suggest no effect on bone loss.
Topics: Adolescent; Alopecia; Androgen Antagonists; Androgens; Anovulation; Diagnostic Techniques, Endocrine; Female; Hirsutism; Humans; Hyperandrogenism; Menstruation Disturbances; Metformin; Polycystic Ovary Syndrome; United States
PubMed: 26509855
DOI: 10.4158/EP15748.DSC -
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 -
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 -
Molecular and Cellular Endocrinology Apr 2018
Topics: Androgens; Animals; Drug Resistance, Neoplasm; Female; Humans; Male; Mice; Receptors, Androgen
PubMed: 29481861
DOI: 10.1016/j.mce.2018.02.013 -
Internal Medicine Journal Mar 2015Doping in sport is a widespread problem not just among elite athletes, but even more so in recreational sports. In scientific literature, major emphasis is placed on... (Review)
Review
Doping in sport is a widespread problem not just among elite athletes, but even more so in recreational sports. In scientific literature, major emphasis is placed on doping detection, whereas detrimental effects of doping agents on athletes' health are seldom discussed. Androgenic anabolic steroids are well known for their positive effects on muscle mass and strength. Human growth hormone also increases muscle mass, although the majority of that is an increase in extracellular fluid and not the functional muscle mass. In recreational athletes, growth hormone does not have major effect on muscle strength, power or aerobic capacity, but stimulates anaerobic exercise capacity. Erythropoietin administration increases oxygen-carrying capacity of blood improving endurance measures, whereas systemic administration of beta-adrenergic agonists may have positive effect on sprint capacity, and beta-adrenergic antagonists reduce muscle tremor. Thus, there are certain drugs that can improve selective aspects of physical performance. However, most of the doping agents exert serious side-effects, especially when used in combination, at high doses and for a long duration. The extent of long-term health consequences is difficult to predict, but likely to be substantial, especially when gene doping is considered. This review summarises the main groups of doping agents used by athletes, with the main focus on their effects on athletic performance and adverse effects.
Topics: Anabolic Agents; Androgens; Athletes; Body Composition; Cardiovascular Diseases; Doping in Sports; Human Growth Hormone; Humans; Muscle Strength
PubMed: 25369881
DOI: 10.1111/imj.12629