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Biology of Sex Differences Jul 2020Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences... (Review)
Review
Sex hormones and their respective receptors affect vascular function differently in men and women, so it is reasonable to assume they play a role in the sex differences in cardiovascular disease states. This review focuses on how the effects of testosterone on arterial vessels impact the female vasculature. In women with androgen-excess polycystic ovary syndrome, and in transgender men, testosterone exposure is associated with high blood pressure, endothelial dysfunction, and dyslipidemia. These relationships suggest that androgens may exert pathophysiological effects on the female vasculature, and these effects on the female vasculature appear to be independent from other co-morbidities of cardiovascular disease. There is evidence that the engagement of androgens with androgen receptor induces detrimental outcomes in the female cardiovascular system, thereby representing a potential causative link with sex differences and cardiovascular regulation. Gender affirming hormone therapy is the primary medical intervention sought by transgender people to reduce the characteristics of their natal sex and induce those of their desired sex. Transgender men, and women with androgen-excess polycystic ovary syndrome both represent patient groups that experience chronic hyperandrogenism and thus lifelong exposure to significant medical risk. The study of testosterone effects on the female vasculature is relatively new, and a complex picture has begun to emerge. Long-term research in this area is needed for the development of more consistent models and controlled experimental designs that will provide insights into the impact of endogenous androgen concentrations, testosterone doses for hormone therapy, and specific hormone types on function of the female cardiovascular system.
Topics: Androgens; Animals; Female; Humans; Male; Polycystic Ovary Syndrome; Testosterone; Transgender Persons
PubMed: 32727622
DOI: 10.1186/s13293-020-00323-6 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032 -
JBJS Reviews Jun 2024» Testosterone replacement treatment (TRT) and anabolic androgenic steroid (AAS) use is common and possibly increasing.» Diagnosing and treating hypogonadism in men is... (Review)
Review
» Testosterone replacement treatment (TRT) and anabolic androgenic steroid (AAS) use is common and possibly increasing.» Diagnosing and treating hypogonadism in men is controversial.» Hypogonadism and the use of AASs seem to have a detrimental effect on the musculoskeletal system. The current literature on TRT and the musculoskeletal system shows an increased risk of tendon injury.» There may be a role for testosterone supplementation in the postoperative period.
Topics: Humans; Testosterone; Male; Hormone Replacement Therapy; Hypogonadism; Orthopedic Surgeons; Androgens
PubMed: 38889232
DOI: 10.2106/JBJS.RVW.24.00061 -
Biomolecules Nov 2022Common uterine diseases include endometriosis, uterine fibroids, endometrial polyps, endometrial hyperplasia, endometrial cancer, and endometrial dysfunction causing... (Review)
Review
Common uterine diseases include endometriosis, uterine fibroids, endometrial polyps, endometrial hyperplasia, endometrial cancer, and endometrial dysfunction causing infertility. Patients with uterine diseases often suffer from abdominal pain, menorrhagia, infertility and other symptoms, which seriously impair their health and disturb their lives. Androgens play important roles in the normal physiological functions of the uterus and pathological progress of uterine diseases. Androgens in women are synthesized in the ovaries and adrenal glands. The action of androgens in the uterus is mainly mediated by its ligand androgen receptor (AR) that regulates transcription of the target genes. However, much less is known about the signaling pathways through which androgen functions in uterine diseases, and contradictory findings have been reported. This review summarizes and discusses the progress of research on androgens and the involvement of AR in uterine diseases. Future studies should focus on developing new therapeutic strategies that precisely target specific AR and their related signaling pathways in uterine diseases.
Topics: Humans; Female; Androgens; Uterine Diseases; Endometrium; Uterus; Infertility
PubMed: 36358974
DOI: 10.3390/biom12111624 -
Revista Brasileira de Ginecologia E... Dec 2019
Topics: Androgens; Doping in Sports; Female; Humans
PubMed: 31856285
DOI: 10.1055/s-0039-3401007 -
Biochimie Nov 2023The androgen receptor (AR) plays an essential role in the growth and progression of prostate cancer (CaP). Ligand-activated AR inside the nucleus binds to the androgen... (Review)
Review
The androgen receptor (AR) plays an essential role in the growth and progression of prostate cancer (CaP). Ligand-activated AR inside the nucleus binds to the androgen response element (ARE) of the target genes in dimeric form and recruits transcriptional machinery to facilitate gene transcription. Pharmacological compounds that inhibit the AR action either bind to the ligand binding domain (LBD) or interfere with the interactions of AR with other co-regulatory proteins, slowing the progression of the disease. However, the emergence of resistance to conventional treatment makes clinical management of CaP difficult. Resistance has been associated with activation of androgen/AR axis that restores AR transcriptional activity. Activated AR signaling in resistance cases can be mediated by several mechanisms including AR amplification, gain-of-function AR mutations, androgen receptor variant (ARVs), intracrine androgen production, and overexpression of AR coactivators. Importantly, in castration resistant prostate cancer, ARVs lacking the LBD become constitutively active and promote hormone-independent development, underlining the need to concentrate on the other domain or the AR-DNA interface for the identification of novel actionable targets. In this review, we highlight the plasticity of AR-DNA binding and explain how fine-tuning AR's cooperative interactions with DNA translate into developing an alternative strategy to antagonize AR activity.
Topics: Male; Humans; Receptors, Androgen; Androgens; Ligands; Prostatic Neoplasms; DNA; Response Elements; Cell Line, Tumor
PubMed: 37460038
DOI: 10.1016/j.biochi.2023.07.012 -
Frontiers in Endocrinology 2020Androgens are some of the most important sex hormones in men, and they maintain important physiological activities in the human body. Cognitive impairment is one of the... (Review)
Review
Androgens are some of the most important sex hormones in men, and they maintain important physiological activities in the human body. Cognitive impairment is one of the most common manifestations of aging in the elderly population and an important factor affecting the quality of life of elderly individuals. The levels of sex hormones in elderly people decrease with age, and low levels of androgens in older male individuals have been closely linked to the development of cognitive impairment. Basic studies have shown that androgens have neuroprotective effects and that androgen deficiency impairs cognitive function by increasing oxidative stress and decreasing synaptic plasticity, among other effects. Additionally, clinical studies have also shown that androgen deficiency is closely related to cognitive impairment. This article reviews the relationship between low androgen levels and cognitive impairment, their potential mechanisms, and the effects of testosterone supplementation in improving cognition.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Androgens; Animals; Cognition; Cognitive Dysfunction; Disease Models, Animal; Humans; Male; Neuroprotection; Quality of Life; Testosterone; Treatment Outcome
PubMed: 33281745
DOI: 10.3389/fendo.2020.586909 -
Sexual Medicine Reviews Oct 2022For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders,... (Review)
Review
INTRODUCTION
For several decades, testosterone and its synthetic derivatives have been used for anabolic and androgenic purposes. Initially restricted to professional bodybuilders, these substances gradually became more popular with recreational weightlifters. Considering its increasing prevalence, the consumption of anabolic androgenic steroids (AAS) has become a matter of great concern. Although most side effects are mild and reversible, some of them can cause permanent damage or can be potentially life threatening.
OBJECTIVES
To review and summarize medical literature regarding misuse and abuse of testosterone and other androgens, in order to provide evidence-based information on the main topics related to this subject, such as how to identify and how to deal with these patients, and to elucidate the multiple possible adverse effects secondary to this practice.
METHODS
Key studies were retrieved from PubMed (1989-2021) with reference searches from relevant articles. Search terms included "hypogonadism", "anabolic androgenic steroids", "androgens", "misuse AND testosterone", "abuse AND testosterone", and "side effects AND testosterone".
RESULTS
There is a significant lack of information in the peer-reviewed literature describing demographic data, implications for different organ systems and the management of current or former AAS users; however, androgen abuse has been already linked to a wide variety of cardiovascular diseases, metabolic, endocrine, neurological, psychiatric and liver disorders. Despite all this, most physicians still feel uncomfortable and hesitate to discuss the issue with patients.
CONCLUSIONS
The chronic use of high doses of AAS is associated with adverse effects in several organ systems; however, there are still many gaps in our knowledge about the long-term consequences of this practice and how to deal with these patients. Healthcare professionals have a crucial role in combating this public health problem, recognizing and preventing the spread of androgen abuse. Linhares BL, Miranda EP, Cintra AR, et al. Use, Misuse and Abuse of Testosterone and Other Androgens. Sex Med Rev 2022;10:583-595.
Topics: Anabolic Agents; Androgens; Humans; Hypogonadism; Testosterone; Testosterone Congeners
PubMed: 34887237
DOI: 10.1016/j.sxmr.2021.10.002 -
Endocrine Reviews Jun 2020We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss... (Review)
Review
We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.
Topics: Adolescent; Androgens; Child; Child, Preschool; Hormone Replacement Therapy; Humans; Hypogonadism; Infant; Klinefelter Syndrome; Male; Puberty; Sexual Development; Testosterone
PubMed: 32115641
DOI: 10.1210/endrev/bnaa003 -
International Journal of Molecular... Nov 2022Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.
Topics: Female; Humans; Polycystic Ovary Syndrome; Hirsutism; Anovulation; Androgens; Hyperinsulinism
PubMed: 36498989
DOI: 10.3390/ijms232314663