-
Andrology Nov 2020The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed... (Review)
Review
BACKGROUND
The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM).
OBJECTIVES
The aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects.
MATERIALS AND METHODS
We have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks.
RESULTS
TRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non-randomized clinical studies and observational studies. This is the case for the safety of a long-term TRT in late-onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure.
CONCLUSION
Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.
Topics: Clinical Decision-Making; Dosage Forms; Drug Administration Routes; Drug Compounding; Eunuchism; Hormone Replacement Therapy; Humans; Male; Risk Assessment; Risk Factors; Testosterone; Treatment Outcome
PubMed: 32068334
DOI: 10.1111/andr.12774 -
Nutrients Jun 2022Intermittent fasting is a popular diet for weight loss, but concerns have been raised regarding the effects of fasting on the reproductive health of women and men.... (Review)
Review
Intermittent fasting is a popular diet for weight loss, but concerns have been raised regarding the effects of fasting on the reproductive health of women and men. Accordingly, we conducted this literature review to clarify the effects of fasting on reproductive hormone levels in humans. Our results suggest that intermittent fasting decreases androgen markers (i.e., testosterone and the free androgen index (FAI)) while increasing sex hormone-binding globulin (SHBG) levels in premenopausal females with obesity. This effect was more likely to occur when food consumption was confined to earlier in the day (eating all food before 4 pm). In contrast, fasting did not have any effect on estrogen, gonadotropins, or prolactin levels in women. As for men, intermittent fasting reduced testosterone levels in lean, physically active, young males, but it did not affect SHBG concentrations. Interestingly, muscle mass and muscular strength were not negatively affected by these reductions in testosterone. In interpreting these findings, it is important to note that very few studies have been conducted on this topic. Thus, it is difficult to draw solid conclusions at present. From the limited data presented here, it is possible that intermittent fasting may decrease androgen markers in both genders. If this is the case, these results would have varied health implications. On the one hand, fasting may prove to be a valuable tool for treating hyperandrogenism in females with polycystic ovarian syndrome (PCOS) by improving menstruation and fertility. On the other hand, fasting may be shown to decrease androgens among males, which could negatively affect metabolic health and libido. More research is warranted to confirm these preliminary findings.
Topics: Androgens; Body Mass Index; Fasting; Female; Humans; Hyperandrogenism; Male; Polycystic Ovary Syndrome; Testosterone
PubMed: 35684143
DOI: 10.3390/nu14112343 -
The Yale Journal of Biology and Medicine Sep 2020Unintended pregnancy is a global public health problem. Despite a variety of female contraceptive options, male contraceptive options are limited to the condom and... (Review)
Review
Unintended pregnancy is a global public health problem. Despite a variety of female contraceptive options, male contraceptive options are limited to the condom and vasectomy. Condoms have high failure rates and surgical vasectomy is not reliably reversible. There is a global need and desire for novel male contraceptive methods. Hormonal methods have progressed the furthest in clinical development and androgen plus progestin formulations hold promise as a marketable, reversible male contraceptive over the next decade. Investigators have tested androgen plus progestin approaches using oral, transdermal, subdermal, and injectable drug formulations and demonstrated the short-term safety and reversibility of hormonal male contraception. The most commonly reported side effects associated with hormonal male contraception include weight gain, acne, slight suppression of serum high-density cholesterol, mood changes, and changes in libido. Efficacy trials of hormonal male contraceptives have demonstrated contraceptive efficacy rates greater than that of condoms. Although there has been less progression in the development of nonhormonal male contraceptives, potentially reversible vaso-occlusive methods are currently in clinical trials in some countries. Various studies have confirmed both men and women's desire for novel male contraceptives. Barriers to development include an absence of investment from pharmaceutical companies, concerns regarding side effects and spermatogenic rebound with hormonal methods, and lack of clear reversibility and proven effectiveness of nonhormonal methods. The ultimate availability of male contraceptives could have an important impact on decreasing global unintended pregnancy rates (currently 40% of all pregnancies) and will be a step towards reproductive justice and greater equity in family planning.
Topics: Contraception; Family Planning Services; Female; Humans; Male; Pregnancy
PubMed: 33005125
DOI: No ID Found -
Fertility and Sterility Jan 2020Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or... (Review)
Review
Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Clinical Trials as Topic; Finasteride; Humans; Male; Observational Studies as Topic; Prostatic Hyperplasia; Sexual Dysfunction, Physiological; Syndrome; Withholding Treatment
PubMed: 32033719
DOI: 10.1016/j.fertnstert.2019.11.030 -
The Journal of Clinical Endocrinology... May 2022Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of... (Review)
Review
CONTEXT
Androgen prohormones such as dehydroepiandrosterone (DHEA) increase in early puberty, peak in the second and third decade, and thereafter decline, independent of menopausal status. Investigators have examined their potential beneficial effects in normal women and those with DHEA-deficient states.
EVIDENCE ACQUISITION
A review of the literature from 1985 to 2021 on the potential benefits and risks of androgen prohormones in women.
EVIDENCE SYNTHESIS
Studies have examined the potential benefit of DHEA therapy for anti-aging, sexual dysfunction, infertility, metabolic bone health, cognition, and wellbeing in hormone-deficient states such as primary adrenal insufficiency, hypopituitarism, and anorexia as well as administration to normal women across the lifespan.
CONCLUSIONS
Data support small benefits in quality of life and mood but not for anxiety or sexual function in women with primary or secondary adrenal insufficiency or anorexia. No consistent beneficial effects of DHEA administration have been observed for menopausal symptoms, sexual function, cognition, or overall wellbeing in normal women. Local administration of DHEA shows benefit in vulvovaginal atrophy. Use of DHEA to improve induction of ovulation response in women with diminished ovarian reserve is not recommended. Risks of high physiologic or pharmacologic use of DHEA include androgenic and estrogenic side effects which are of concern for long-term administration.
CLINICAL CASE
A 49-year-old woman with Addison's disease who is on low dose estrogen with cyclic progesterone therapy for menopausal symptoms returns for follow-up. She is on a stable glucocorticoid replacement strategy of hydrocortisone 10 mg in the morning and 5 mg in the early afternoon and fludrocortisone 0.05 mg each morning. She has read on the internet that additional therapy with DHEA may help her overall quality of life and libido. She asks whether she should add this therapy to her regimen and at what dose.
Topics: Androgens; Anorexia; Dehydroepiandrosterone; Estrogens; Female; Hormone Replacement Therapy; Humans; Middle Aged; Quality of Life
PubMed: 35254428
DOI: 10.1210/clinem/dgac130 -
International Journal of Molecular... Mar 2022Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low... (Review)
Review
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.
Topics: Aged; Aging; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Testosterone
PubMed: 35408895
DOI: 10.3390/ijms23073535 -
Nutrients Mar 2020Low energy availability (EA) underpins the female and male athlete triad and relative energy deficiency in sport (RED-S). The condition arises when insufficient calories... (Review)
Review
Low energy availability (EA) underpins the female and male athlete triad and relative energy deficiency in sport (RED-S). The condition arises when insufficient calories are consumed to support exercise energy expenditure, resulting in compromised physiological processes, such as menstrual irregularities in active females. The health concerns associated with longstanding low EA include menstrual/libido, gastrointestinal and cardiovascular dysfunction and compromised bone health, all of which can contribute to impaired sporting performance. This narrative review provides an update of our previous review on the prevalence and risk of low EA, within-day energy deficiency, and the potential impact of low EA on performance. The methods to assess EA remain a challenge and contribute to the methodological difficulties in identifying "true" low EA. Screening female athletic groups using a validated screening tool such as the Low Energy Availability in Females Questionnaire (LEAF-Q) has shown promise in identifying endurance athletes at risk of low EA. Knowledge of RED-S and its potential implications for performance is low among coaches and athletes alike. Development of sport and gender-specific screening tools to identify adolescent and senior athletes in different sports at risk of RED-S is warranted. Education initiatives are required to raise awareness among coaches and athletes of the importance of appropriate dietary strategies to ensure that sufficient calories are consumed to support training.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Athletes; Athletic Performance; Energy Intake; Energy Metabolism; Feeding and Eating Disorders; Female; Humans; Male; Malnutrition; Middle Aged; Nutritional Status; Prevalence; Sports Nutritional Physiological Phenomena; Young Adult
PubMed: 32245088
DOI: 10.3390/nu12030835 -
Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.International Journal of Molecular... Mar 2021Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40... (Review)
Review
Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4-30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave's disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto's type thyroid antibodies and has a prevalence of 10-40%. 21OH-Antibodies in Addison's disease (AD) can develop in association to APS-2.
Topics: Amenorrhea; Autoantibodies; Autoimmune Diseases; Female; Hashimoto Disease; Humans; Menopause, Premature; Ovary; Polyendocrinopathies, Autoimmune; Primary Ovarian Insufficiency
PubMed: 33807517
DOI: 10.3390/ijms22052594 -
Cell Aug 2023Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and...
Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTpr neurons, which innervate POA neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTpr neurons are upstream of POA neurons, and BNSTpr-released substance P following mate recognition potentiates activation of POA neurons through Tacr1 to initiate mating. Experimental activation of POA neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.
Topics: Animals; Male; Neurons; Reward; Sexual Behavior, Animal; Mice; Neural Pathways
PubMed: 37572660
DOI: 10.1016/j.cell.2023.07.021