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Frontiers in Endocrinology 2022Rates of unplanned pregnancies are high and stagnant globally, burdening women, families and the environment. Local limitations placed upon contraceptive access and...
Rates of unplanned pregnancies are high and stagnant globally, burdening women, families and the environment. Local limitations placed upon contraceptive access and abortion services exacerbate global disparities for women. Despite survey data suggesting men and their partners are eager for expanded male contraceptive options, efforts to develop such agents have been stymied by a paucity of monetary investment. Modern male hormonal contraception, like female hormonal methods, relies upon exogenous progestins to suppress the hypothalamic-pituitary-gonadal axis, in turn suppressing testicular testosterone production and sperm maturation. Addition of an androgen augments gonadotropin suppression, more effectively suppressing spermatogenesis in men, and provides androgenic support for male physiology. Previous contraceptive efficacy studies in couples have shown that hormonal male methods are effective and reversible. Recent efforts have been directed at addressing potential user and regulatory concerns by utilizing novel steroids and varied routes of hormone delivery. Provision of effective contraceptive options for men and women is an urgent public health need. Recognizing and addressing the gaps in our contraceptive options and engaging men in family planning will help reduce rates of unplanned pregnancies in the coming decades.
Topics: Androgens; Contraception; Contraceptive Agents, Male; Female; Hormonal Contraception; Humans; Male; Pregnancy; Spermatogenesis; Testosterone
PubMed: 35721718
DOI: 10.3389/fendo.2022.891589 -
Journal of Obstetrics and Gynaecology... Mar 2017Androgens, both in excessive and depleted states, have been implicated in female reproductive health disorders. As such, serum testosterone measurements are frequently... (Review)
Review
Androgens, both in excessive and depleted states, have been implicated in female reproductive health disorders. As such, serum testosterone measurements are frequently ordered by physicians in cases of sexual dysfunction and in women presenting with hirsutism. Commercially available androgen assays have significant limitations in the female population. Furthermore, the measurements themselves are not always informative in patient diagnosis, treatment, or prognosis. This article reviews the limitations of serum androgen measurements in women suspected to have elevated or reduced androgen action. Finally, we consider when therapeutic use of androgen replacement may be appropriate for women with sexual interest/arousal disorders.
Topics: Androgens; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Estrogen Replacement Therapy; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Radioimmunoassay; Sexual Dysfunctions, Psychological; Testosterone
PubMed: 28343552
DOI: 10.1016/j.jogc.2017.01.006 -
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 of Hormone Research 2019Differences between males and females are commonly attributed to sexual hormones. Androgens are responsible for the development of primary and secondary sexual... (Review)
Review
Differences between males and females are commonly attributed to sexual hormones. Androgens are responsible for the development of primary and secondary sexual characteristics in males, whereas they influence sexual behaviour, glycaemic control, lipid profile, bone metabolism and erythropoiesis in both sexes. In this chapter, we discuss preclinical and clinical data on sex-specific androgen metabolism and androgen effect on body composition.
Topics: Androgens; Animals; Body Composition; Female; Humans; Male; Sex Characteristics
PubMed: 31499499
DOI: 10.1159/000494900 -
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 -
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 -
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 -
Endocrine-related Cancer Jul 2016In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of... (Review)
Review
In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.
Topics: Androgens; Animals; Endometrial Neoplasms; Estrogens; Female; Humans; Receptors, Androgen
PubMed: 27287451
DOI: 10.1530/ERC-15-0470