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Sports Medicine (Auckland, N.Z.) Feb 2021Males enjoy physical performance advantages over females within competitive sport. The sex-based segregation into male and female sporting categories does not account... (Review)
Review
Males enjoy physical performance advantages over females within competitive sport. The sex-based segregation into male and female sporting categories does not account for transgender persons who experience incongruence between their biological sex and their experienced gender identity. Accordingly, the International Olympic Committee (IOC) determined criteria by which a transgender woman may be eligible to compete in the female category, requiring total serum testosterone levels to be suppressed below 10 nmol/L for at least 12 months prior to and during competition. Whether this regulation removes the male performance advantage has not been scrutinized. Here, we review how differences in biological characteristics between biological males and females affect sporting performance and assess whether evidence exists to support the assumption that testosterone suppression in transgender women removes the male performance advantage and thus delivers fair and safe competition. We report that the performance gap between males and females becomes significant at puberty and often amounts to 10-50% depending on sport. The performance gap is more pronounced in sporting activities relying on muscle mass and explosive strength, particularly in the upper body. Longitudinal studies examining the effects of testosterone suppression on muscle mass and strength in transgender women consistently show very modest changes, where the loss of lean body mass, muscle area and strength typically amounts to approximately 5% after 12 months of treatment. Thus, the muscular advantage enjoyed by transgender women is only minimally reduced when testosterone is suppressed. Sports organizations should consider this evidence when reassessing current policies regarding participation of transgender women in the female category of sport.
Topics: Emotions; Female; Gender Identity; Humans; Male; Sports; Testosterone; Transgender Persons
PubMed: 33289906
DOI: 10.1007/s40279-020-01389-3 -
Andrology Mar 2022Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism.
METHODS
The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects.
RESULTS
We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.
CONCLUSION
Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.
Topics: Clomiphene; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Testosterone
PubMed: 34933414
DOI: 10.1111/andr.13146 -
Actas Dermo-sifiliograficas Jun 2020Oral contraceptives combine estrogen and progesterone to suppress ovulation. Synthetic forms are usually used. In dermatology, oral contraceptives are prescribed for 2... (Review)
Review
Oral contraceptives combine estrogen and progesterone to suppress ovulation. Synthetic forms are usually used. In dermatology, oral contraceptives are prescribed for 2 main reasons: to prevent pregnancy when teratogenic drugs must be taken and to treat skin manifestations of hyperandrogenism. Most oral contraceptives improve both acne and hirsutism, but the androgenic effect of progestogens - particularly if the contraceptive contains first- or second-generation progestogens- can trigger or exacerbate acne. One of the most serious side effects of oral contraceptives, thrombosis, is mainly caused by the estrogen component and its dose. If we mainly consider a contraceptive's thrombotic profile when prescribing, the choice would be to have 30μg or less of ethinyl estradiol combined with levonorgestrel. On the other hand, if our main objective is to treat signs of androgenization, we would prefer contraceptives containing progestogens with antiandrogenic effects.
Topics: Contraceptives, Oral; Dermatology; Ethinyl Estradiol; Female; Humans; Levonorgestrel; Pregnancy; Progesterone
PubMed: 32404240
DOI: 10.1016/j.ad.2019.06.006 -
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 -
Neurobiology of Disease Jul 2020Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease...
Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple sclerosis. The neuroprotective role of androgens, including testosterone and its metabolite dihydrotestosterone (DHT), has been increasingly demonstrated in these diseases, but few studies investigated the effects of androgen on neuroinflammation. This study investigated the role of DHT in lipopolysaccharide (LPS)-induced neuroinflammation, neuronal damage and behavioral dysfunction, as well as underlying mechanisms. We showed that DHT inhibited LPS-induced release of proinflammatory factors, including TNF-α, IL-1β, IL-6; iNOS, COX-2, NO, and PGE2 in BV2 cells and primary microglia by suppressing the TLR4-mediated NF-κB and MAPK p38 signaling pathways, thus protecting SH-SY5Y neurons from inflammatory damage induced by activated microglia. In an LPS-induced neuroinflammation mouse model, endogenous DHT depletion by castration exacerbated inflammatory responses by upregulating the levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2 in the serum and brain by increasing the LR4-mediated NF-κB and MAPK pathway activation, but these effects were restored by exogenous DHT supplementation. Moreover, DHT also regulated the mRNA levels of the anti-inflammatory cytokines IL-10 and IL-13 in the brain. In addition, DHT modulated the expression of Aβ, the apoptotic proteins caspase-3, Bcl-2, and Bax, and synaptophysin, as well as neuronal damage in LPS-treated mouse brains. Further behavioral tests revealed that DHT ameliorated LPS-induced spatial and learning impairment and motor incoordination, and partly improved the locomotor activity in LPS-injected mice. Therefore, this study suggests that DHT exerts anti-neuroinflammatory and neuroprotective effects; thus, androgen replacement therapy is a potential therapeutic strategy for improving cognitive and behavioral function in neuroinflammation-related diseases.
Topics: Androgens; Animals; Anti-Inflammatory Agents; Brain; Cyclooxygenase 2; Cytokines; Dihydrotestosterone; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Microglia; NF-kappa B; Neurons; Neuroprotection; Neuroprotective Agents; Nitric Oxide Synthase Type II; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 32087283
DOI: 10.1016/j.nbd.2020.104814 -
Cureus Oct 2023Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls... (Review)
Review
Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls by the enlargement of the breasts (thelarche) in girls and in boys by the enlargement of the testes in either volume or length (testicular volume = 4 mL, testicular length = 25 mm, or both). Two types of PP are recognized - namely central PP (CPP) and peripheral PP (PPP). This paper aims to describe the clinical findings and laboratory workup of PP and to illustrate the new trends in the management of precocious sexual maturation. Gonadotropin-releasing hormone (GnRH)-independent type (PPP) refers to the development of early pubertal maturation not related to the central activation of the hypothalamic-pituitary-gonadal (HPG) axis. It is classified into genetic or acquired disorders. The most common forms of congenital or genetic causes involve McCune-Albright syndrome (MAS), familial male-limited PP, and congenital adrenal hyperplasia. The acquired causes include exogenous exposure to androgens, functioning tumors or cysts, and the pseudo-PP of profound primary hypothyroidism. On the other hand, CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such as MKRN3, DLK1, or KISS1;as a part of mutations in theepigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others. A full, detailed history and physical examination should be taken. Furthermore, several investigations should be conducted for both types of PP, including the estimation of serum gonadotropins such as luteinizing and follicle-stimulating hormones and sex steroids, in addition to a radiographic workup and thyroid function tests. Treatment depends on the type of PP: Long-acting GnRHa, either intramuscularly or implanted, is the norm of care for CPP management, while in PPP, especially in congenital adrenal hyperplasia, the goal of management is to suppress adrenal androgen secretion by glucocorticoids. In addition, anastrozole and letrozole - third-generation aromatase inhibitors - are more potent for MAS.
PubMed: 38021712
DOI: 10.7759/cureus.47485 -
Endocrinology and Metabolism Clinics of... Mar 2022All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations, and relieve symptoms in most... (Review)
Review
All approved testosterone replacement methods, when used according to recommendations, can restore normal serum testosterone concentrations, and relieve symptoms in most hypogonadal men. Selection of the method depends on the patient's preference with advice from the physician. Dose adjustment is possible with most delivery methods but may not be necessary in all hypogonadal men. The use of hepatotoxic androgens must be avoided. Testosterone treatment induces reversible suppression of spermatogenesis; if fertility is desired in the near future, human chronic gonadotropin, selective estrogen receptor modulator, estrogen antagonist, or an aromatase inhibitor that stimulates endogenous testosterone production may be used.
Topics: Androgens; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Spermatogenesis; Testosterone
PubMed: 35216722
DOI: 10.1016/j.ecl.2021.11.005 -
Nature Genetics May 2022HOXB13, a homeodomain transcription factor, critically regulates androgen receptor (AR) activities and androgen-dependent prostate cancer (PCa) growth. However, its...
HOXB13, a homeodomain transcription factor, critically regulates androgen receptor (AR) activities and androgen-dependent prostate cancer (PCa) growth. However, its functions in AR-independent contexts remain elusive. Here we report HOXB13 interaction with histone deacetylase HDAC3, which is disrupted by the HOXB13 G84E mutation that has been associated with early-onset PCa. Independently of AR, HOXB13 recruits HDAC3 to lipogenic enhancers to catalyze histone deacetylation and suppress lipogenic regulators such as fatty acid synthase. Analysis of human tissues reveals that the HOXB13 gene is hypermethylated and downregulated in approximately 30% of metastatic castration-resistant PCa. HOXB13 loss or G84E mutation leads to lipid accumulation in PCa cells, thereby promoting cell motility and xenograft tumor metastasis, which is mitigated by pharmaceutical inhibition of fatty acid synthase. In summary, we present evidence that HOXB13 recruits HDAC3 to suppress de novo lipogenesis and inhibit tumor metastasis and that lipogenic pathway inhibitors may be useful to treat HOXB13-low PCa.
Topics: Androgens; Cell Line, Tumor; Epigenesis, Genetic; Histone Deacetylases; Homeodomain Proteins; Humans; Lipogenesis; Male; Prostatic Neoplasms; Receptors, Androgen; Transcription Factors
PubMed: 35468964
DOI: 10.1038/s41588-022-01045-8 -
Journal of Cosmetic Dermatology Aug 2022The humans have been disproportionately affected by the coronavirus disease (COVID-19) pandemic. The novel coronavirus or the severe acute respiratory syndrome... (Review)
Review
BACKGROUND
The humans have been disproportionately affected by the coronavirus disease (COVID-19) pandemic. The novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) causing coronavirus disease (COVID-19) has spread across the globe. Androgens have been suggested to have a role in COVID-19 pathogenesis.
OBJECTIVE
The objective of this review article is to study the link between androgens and COVID-19.
METHODOLOGY
PubMed and Google Scholar search was performed to retrieve literature related to the topic. Review articles, clinical trials, retrospective studies, observational studies, and case-control studies were considered for the review.
RESULTS
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected men are more inclined to be hospitalized for intensive care unit (ICU) as compared with women. This difference in the ICU admissions provides some clue for possible influence of androgens in the severity of COVID-19. The contribution of androgen and androgen receptor in COVID-19 disease and its severity, as well as the numerous medications targeting androgen and its receptor for lowering COVID-19 disease severity, are discussed in this review. Available literature suggests the role of androgen in the pathogenesis and severity of COVID-19. Sensitivity for androgen may be an important factor in regulating the severity of COVID-19 disease.
CONCLUSION
There is a scope for the development of COVID-19 treatments based on androgen suppression. Clinical trials may furnish pivotal data and add more evidence-based options for the management of COVID-19.
Topics: Androgens; COVID-19; Female; Humans; Male; RNA, Viral; Retrospective Studies; SARS-CoV-2
PubMed: 35576054
DOI: 10.1111/jocd.15090 -
Journal of Biomedical Science Mar 2022Androgenetic alopecia (AGA) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs)...
BACKGROUND
Androgenetic alopecia (AGA) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs) located in the base of hair follicles. DHT causes DPC senescence in AGA through mitochondrial dysfunction. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the protective role of cyanidins on DHT-induced mitochondrial dysfunction and DPC senescence and the regulatory mechanism involved.
METHODS
DPCs were used to investigate the effect of DHT on mitochondrial dysfunction with MitoSOX and Rhod-2 staining. Senescence-associated β-galactosidase activity assay was performed to examine the involvement of membrane AR-mediated signaling in DHT-induced DPC senescence. AGA mice model was used to study the cyanidins on DHT-induced hair growth deceleration.
RESULTS
Cyanidin 3-O-arabinoside (C3A) effectively decreased DHT-induced mtROS accumulation in DPCs, and C3A reversed the DHT-induced DPC senescence. Excessive mitochondrial calcium accumulation was blocked by C3A. C3A inhibited p38-mediated voltage-dependent anion channel 1 (VDAC1) expression that contributes to mitochondria-associated ER membrane (MAM) formation and transfer of calcium via VDAC1-IP3R1 interactions. DHT-induced MAM formation resulted in increase of DPC senescence. In AGA mice models, C3A restored DHT-induced hair growth deceleration, which activated hair follicle stem cell proliferation.
CONCLUSIONS
C3A is a promising natural compound for AGA treatments against DHT-induced DPC senescence through reduction of MAM formation and mitochondrial dysfunction.
Topics: Animals; Anthocyanins; Cellular Senescence; Dihydrotestosterone; Hair Follicle; Mice; Mitochondria
PubMed: 35255899
DOI: 10.1186/s12929-022-00800-7