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International Journal of Molecular... Dec 2022Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the... (Review)
Review
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.
Topics: Humans; Male; Female; Mice; Animals; Testosterone; Androgens; Virilism; Mutation; Dihydrotestosterone; 17-Hydroxysteroid Dehydrogenases
PubMed: 36555196
DOI: 10.3390/ijms232415555 -
American Journal of Physiology.... Jun 2021Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin...
Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (). Fasting blood was collected on , , , , and , and females were euthanized on . On , TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations () were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated and in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT. Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.
Topics: Adipose Tissue; Animals; Female; Injections, Intramuscular; Insulin; Insulin Resistance; Liver; Signal Transduction; Swine; Testosterone; Virilism
PubMed: 33900852
DOI: 10.1152/ajpendo.00281.2020 -
Canadian Journal of Psychiatry. Revue... May 2021Suicide in Canadian men is high and rising. Research consistently indicates increased suicide risk in male subgroups including sexual minority, Indigenous, middle-aged,... (Review)
Review
OBJECTIVE
Suicide in Canadian men is high and rising. Research consistently indicates increased suicide risk in male subgroups including sexual minority, Indigenous, middle-aged, and military men. The current scoping review addresses the research question: Among male subgroups featured in Canadian suicide research, what are the key findings to inform suicide prevention efforts?.
METHOD
A scoping review was undertaken in accord with PRISMA-ScR guidelines. Structured searches were conducted in CIHAHL, Medline, PsychInfo, and Web of Science to identify studies reporting suicidality (suicidal ideation, plans and/or attempts) and suicide among men in Canada. Inclusion criteria comprised primary empirical studies featuring Canadian male subgroups published in English from 2009 to 2020 inclusive.
RESULTS
Sixty-eight articles met the inclusion criteria, highlighting significant rates of male suicidality and/or suicide in 3 categories: (1) health inequities ( = 29); (2) age-specific ( = 30); and (3) occupation ( = 9). The health inequities category included sexual minority men, Indigenous, and other marginalized males (i.e., homeless, immigrant men, and men who use opiates). Age-specific men focused on adolescents and youth, and middle-aged and older males. Active military, veterans, and first responders featured in the occupation category. Studies compared at risk male subgroups to females, general male populations, and/or other marginalized groups in emphasizing mental health disparities and increased suicide risk. Some men's suboptimal connections to existing mental health care services were also highlighted.
CONCLUSION
While male subgroups who are vulnerable to suicidality and suicide were consistently described, these insights have not translated to tailored upstream suicide prevention services for Canadian boys and men. There may be some important gains through integrating social and mental health care services for marginalized men, implementing school-based masculinity programs for adolescent males, orientating clinicians to the potential for men's mid-life suicide risks (i.e., separation, bereavement, retirement) and lobbying employers to norm help-seeking among activate military, veterans, and first responder males.
Topics: Adolescent; Aged; Canada; Female; Humans; Male; Masculinity; Men's Health; Middle Aged; Suicidal Ideation; Suicide Prevention
PubMed: 33719600
DOI: 10.1177/07067437211000631 -
California Medicine Feb 1967In normal females, androstenedione from both the adrenal cortex and ovary, as a result of peripheral conversion, is the source of the majority of biologically active...
In normal females, androstenedione from both the adrenal cortex and ovary, as a result of peripheral conversion, is the source of the majority of biologically active testosterone in the circulation. The control of the secretion of precursor steroid and androgenic hormone (testosterone) in females is not clear at this time. There are a number of possibilities to explain various types of hirsutism and virilization. The presence of true virilization indicates a significant disorder and requires complete investigation. The presence of increased amounts of 17-ketosteroids in the urine implicates the adrenal cortex as a source of the pathologic manifestations. The suppressibility of elevated 17-ketosteroids with cortisol analogues aids in distinguishing between adrenal hyperplasia and autonomous neoplasm of the adrenal cortex. By far the most common entity in this area is simple hirsutism without virilization. Although our knowledge of this disorder is quite incomplete, conservative management is indicated. Further progress in this field is rapidly occurring. An informed clinician can do an adequate job of diagnosis and treatment with the clinical and laboratory tools generally available.
Topics: Androgens; Female; Hirsutism; Humans; Virilism
PubMed: 6044295
DOI: No ID Found -
Transfusion Nov 2021FDA guidelines limit the use of blood from donors taking testosterone replacement therapy (TRT) to red blood cell (RBC) concentrates, whereas plasma and platelets are...
BACKGROUND
FDA guidelines limit the use of blood from donors taking testosterone replacement therapy (TRT) to red blood cell (RBC) concentrates, whereas plasma and platelets are discarded. The purpose of this study is to bring awareness to above-average free testosterone concentrations in RBC units from TRT donors.
STUDY DESIGN
We quantified the concentrations of free (bioavailable; pg/ml) and total (protein bound and free; ng/dl) testosterone in plasma (frozen within 24 h) and supernatants from 42-day stored leukocyte-reduced RBC units from 17 TRT male donors and 17 matched controls (no TRT). Total testosterone concentrations were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Free testosterone concentrations were quantified in the same samples using equilibrium dialysis/LC-MS/MS.
RESULTS
Plasma free and total testosterone concentrations in TRT donors were 2.9 and 1.8 times higher than that of controls. Total testosterone concentrations in RBC supernatants were about 30% of that of plasma. In contrast, free testosterone concentrations in RBC supernatants were 80%-100% of that of plasma and were significantly (p = .005) higher in TRT compared with controls (252.3 ± 245.3 vs. 103.4 ± 88.2 pg/ml). Supraphysiological free testosterone concentrations (>244 pg/ml) in RBC supernatants were observed in five TRT donors and two control donors.
CONCLUSIONS
RBC units from TRT donors may contain supraphysiological concentrations of free testosterone. This may be resolved by avoiding blood collections soon after testosterone dosing and by enhanced screening of TRT donors. These data establish a rationale for new studies and reexamination of the current guidelines concerning the utilization of blood components from TRT donors.
Topics: Blood Donors; Chromatography, Liquid; Erythrocytes; Hormone Replacement Therapy; Humans; Male; Masculinity; Tandem Mass Spectrometry; Testosterone
PubMed: 34519056
DOI: 10.1111/trf.16658 -
American Journal of Men's Health Jan 2016Although men's cancer experiences have received limited attention within the field of psychosocial oncology, increasing attention is being devoted to the development and... (Review)
Review
Although men's cancer experiences have received limited attention within the field of psychosocial oncology, increasing attention is being devoted to the development and evaluation of men-centered programs. This scoping review describes this emergent body of literature, detailing the focus, participation, and impact of interventions designed to help men with cancer build illness-specific knowledge, adapt to illness, manage side effects, distress, and uncertainty, sustain relationships, and more. Striving to build on existing knowledge, research gaps and opportunities are discussed, including a need for stronger methodologies, more tailored and targeted supports, attention to the experiences of men with nonprostate cancers, and the explicit integration of gender analyses in the research process.
Topics: Humans; Male; Masculinity; Men's Health; Neoplasms; Social Support
PubMed: 25389212
DOI: 10.1177/1557988314555361 -
The Journal of Clinical Endocrinology... Apr 2021Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows... (Review)
Review
UNLABELLED
Virilization is the medical term for describing a female who develops characteristics associated with male hormones (androgens) at any age, or when a newborn girl shows signs of prenatal male hormone exposure at birth. In girls, androgen levels are low during pregnancy and childhood. A first physiologic rise of adrenal androgens is observed at the age of 6 to 8 years and reflects functional activation of the zona reticularis of the adrenal cortex at adrenarche, manifesting clinically with first pubic and axillary hairs. Early adrenarche is known as "premature adrenarche." It is mostly idiopathic and of uncertain pathologic relevance but requires the exclusion of other causes of androgen excess (eg, nonclassic congenital adrenal hyperplasia) that might exacerbate clinically into virilization. The second modest physiologic increase of circulating androgens occurs then during pubertal development, which reflects the activation of ovarian steroidogenesis contributing to the peripheral androgen pool. However, at puberty initiation (and beyond), ovarian steroidogenesis is normally devoted to estrogen production for the development of secondary female bodily characteristics (eg, breast development). Serum total testosterone in a young adult woman is therefore about 10- to 20-fold lower than in a young man, whereas midcycle estradiol is about 10- to 20-fold higher. But if androgen production starts too early, progresses rapidly, and in marked excess (usually more than 3 to 5 times above normal), females will manifest with signs of virilization such as masculine habitus, deepening of the voice, severe acne, excessive facial and (male typical) body hair, clitoromegaly, and increased muscle development. Several medical conditions may cause virilization in girls and women, including androgen-producing tumors of the ovaries or adrenal cortex, (non)classical congenital adrenal hyperplasia and, more rarely, other disorders (also referred to as differences) of sex development (DSD). The purpose of this article is to describe the clinical approach to the girl with virilization at puberty, focusing on diagnostic challenges. The review is written from the perspective of the case of an 11.5-year-old girl who was referred to our clinic for progressive, rapid onset clitoromegaly, and was then diagnosed with a complex genetic form of DSD that led to abnormal testosterone production from a dysgenetic gonad at onset of puberty. Her genetic workup revealed a unique translocation of an abnormal duplicated Y-chromosome to a deleted chromosome 9, including the Doublesex and Mab-3 Related Transcription factor 1 (DMRT1) gene.
LEARNING OBJECTIVES
Identify the precise pathophysiologic mechanisms leading to virilization in girls at puberty considering that virilization at puberty may be the first manifestation of an endocrine active tumor or a disorder/difference of sex development (DSD) that remained undiagnosed before and may be life-threatening. Of the DSDs, nonclassical congenital adrenal hyperplasia occurs most often.Provide a step-by-step diagnostic workup plan including repeated and expanded biochemical and genetic tests to solve complex cases.Manage clinical care of a girl virilizing at puberty using an interdisciplinary team approach.Care for complex cases of DSD manifesting at puberty, such as the presented girl with a Turner syndrome-like phenotype and virilization resulting from a complex genetic variation.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Female; Humans; Puberty; Virilism
PubMed: 33367768
DOI: 10.1210/clinem/dgaa948 -
Physiological Research 2011Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The... (Review)
Review
Hyperandrogenic states in pregnancy are almost always the result of a condition that arises during pregnancy. The onset of virilization symptoms is often very fast. The mother is protected against hyperandrogenism by a high level of SHBG, by placental aromatase and a high level of progesterone. The fetus is protected from the mother's hyperandrogenism partly by the placental aromatase, that transforms the androgens into estrogens, and partly by SHGB. Nevertheless there is a significant risk of virilization of the female fetus if the mother's hyperandrogenic state is serious. The most frequent cause of hyperandrogenic states during pregnancy are pregnancy luteoma and hyperreactio luteinalis. Hormonal production is evident in a third of all luteomas, which corresponds to virilization in 25-35 % of mothers with luteoma. The female fetus is afflicted with virilization with two thirds of virilized mothers. Hyperreactio luteinalis is created in connection with a high level of hCG, e.g. during multi-fetus pregnancies. This condition most frequently arises in the third trimester, virilization of the mother occurs in a third of cases. Virilization of the fetus has not yet been described. The most serious cause of hyperandrogenism is represented by ovarian tumors, which are fortunately rare.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenocortical Adenoma; Adrenocortical Carcinoma; Adult; Androgens; Aromatase; Female; Fetus; Humans; Hyperandrogenism; Luteoma; Ovarian Neoplasms; Ovary; Placenta; Pregnancy; Pregnancy Complications; Ultrasonography, Prenatal; Virilism
PubMed: 21114372
DOI: 10.33549/physiolres.932078 -
The British Journal of Sociology Jun 2022Masculinities scholarship tends toward describing autonomy as bound up with hegemonic masculine ideals such as independence, atomization, and self-sufficiency, without...
Masculinities scholarship tends toward describing autonomy as bound up with hegemonic masculine ideals such as independence, atomization, and self-sufficiency, without fully delving into the concept of autonomy. This article offers a more in-depth conceptual treatment of autonomy, compared to its more simplified rendering in the literature on the dominant relational conceptualizations of masculinities. In doing so, we follow recent calls to avoid categorizing men according to typologies of masculinity, drawing instead on feminist theorizations of masculine autonomy and relationality to explore how both manifest in men's lives. We draw on a study of men's drinking practices, with our data coming from focus groups with 101 men in metropolitan and regional/rural Victoria, Australia; but the issues we attend to have relevance, and can be an impetus, for further scholarly thinking about autonomy in men's lives well beyond drinking practices, and in other similar industrialized nations. We explore how masculine autonomy remains an influential and harmful discourse, often impeding possibilities for men's greater intimacy, connection and care and reproducing gendered hierarchies. However, we simultaneously highlight how men are inescapably relationally situated, exposing masculine autonomy as a discursive ideal of valorized forms of masculinity rather than an achievable state in practice. We argue that acknowledging how men are relationally embedded and interdependent in practice offers potential avenues for further fostering men's care, intimacy and relationality, and might work toward ameliorating gendered inequalities that see care work and the work of sustaining relational networks disproportionately falling to women and marginalized men.
Topics: Female; Focus Groups; Humans; Male; Masculinity; Men's Health; Sexual Behavior; Victoria
PubMed: 35690996
DOI: 10.1111/1468-4446.12947 -
British Medical Journal Feb 1980
Review
Topics: Androgens; Drug Therapy, Combination; Ethinyl Estradiol; Female; Hair Removal; Hirsutism; Humans; Polycystic Ovary Syndrome; Prednisolone; Virilism
PubMed: 6988040
DOI: 10.1136/bmj.280.6211.369