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Current Opinion in Endocrine and... Jun 2021Disordered sleep impairs neurocognitive performance, and is now recognized to cause metabolic ill-health. This review assesses the nascent relationship between...
Disordered sleep impairs neurocognitive performance, and is now recognized to cause metabolic ill-health. This review assesses the nascent relationship between insufficient, misaligned, and disrupted sleep with andrological health. High-quality cohort studies show a reduced sperm count in men with sleep disturbances. Well-designed interventional studies show a reduction in testosterone with sleep restriction. Studies of long-term shift workers show no effect of misaligned sleep on mean testosterone concentrations. Men with obstructive sleep apnea (OSA) and more severe hypoxemia have lower testosterone levels, although it is unknown if this relationship is entirely explained by concomitant obesity, or is reversible. Nevertheless, erectile dysfunction, which is common in men with OSA, is clinically improved when OSA is properly treated. Few studies manipulating sleep have been performed in older men, in whom the accumulation of sleep disturbances over decades of life may contribute to age-related illnesses. Improving sleep could ameliorate the development of these disorders.
PubMed: 33937581
DOI: 10.1016/j.coemr.2021.03.002 -
Therapeutic Advances in Drug Safety Aug 2018Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous... (Review)
Review
Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective-destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.
PubMed: 30364888
DOI: 10.1177/2042098618773318 -
Annals of Medicine and Surgery (2012) Jul 2023A common health problem known as polycystic ovarian syndrome (PCOS), is characterized by irregular periods, an excess of androgen production, and polycystic ovaries. It...
A common health problem known as polycystic ovarian syndrome (PCOS), is characterized by irregular periods, an excess of androgen production, and polycystic ovaries. It is one of the most prevalent endocrine disorders in women of reproductive age, affecting 4-20% of women worldwide. Numerous studies have found a connection between the onset and symptoms of PCOS and Vitamin D insufficiency. Vitamin D insufficiency causes calcium dysregulation and follicular arrest in women with PCOS, which is connected to menstrual irregularities and fertility issues. Studies have connected PCOS metabolic alterations to VDR polymorphisms such as iApa-I, Taq-I, Cdx2, and Fok-I. Insulin resistance is directly related to Vitamin D, is one of the most distinctive characteristics of the PCOS phenotype. Thus, it is suggested that Vitamin D therapy may help PCOS patients with their insulin sensitivity. In addition to insulin resistance, cardiovascular issues are a second metabolic disturbance that PCOS patients with low Vitamin D levels experience. Dyslipidemia is not linked to an increased risk of cardiovascular disease in PCOS-affected women. Vitamin D dramatically improves glucose metabolism by increasing insulin production, insulin receptor expression and reducing pro-inflammatory cytokines. The effect of Vitamin D on the metabolic and reproductive dysfunctions associated with PCOS may be mediated by an overall impact on insulin resistance. Vitamin D supplementation improved menstrual periods, increased folliculogenesis, and decreased blood testosterone levels in PCOS patients, all of which had a significant impact on the ability to procreate. As a result, it might be a cutting-edge therapeutic strategy for treating PCOS concurrently.
PubMed: 37427232
DOI: 10.1097/MS9.0000000000000879 -
The American Journal of Pathology Dec 2023Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodeling. The mechanisms underlying this association are still...
Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodeling. The mechanisms underlying this association are still unclear. It is also unclear whether hyperandrogenism and insulin resistance, the two common manifestations of polycystic ovary syndrome, affect uterine SpA remodeling. We verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher fetal mortality. Exposure to DHT and INS dysregulated the expression of angiogenesis-related genes in the uterus and placenta and also decreased expression of endothelial nitric oxide synthase and matrix metallopeptidases 2 and 9, increased fibrotic collagen deposits in the uterus, and reduced expression of marker genes for SpA-associated trophoblast giant cells. These changes were related to a greater proportion of unremodeled uterine SpAs and a smaller proportion of highly remodeled arteries in DHT + INS-exposed rats. Placentas from DHT + INS-exposed rats exhibited decreased basal and labyrinth zone regions, reduced maternal blood spaces, diminished labyrinth vascularity, and an imbalance in the abundance of vascular and smooth muscle proteins. Furthermore, placentas from DHT + INS-exposed rats showed expression of placental insufficiency markers and a significant increase in cell senescence-associated protein levels. Altogether, this work demonstrates that increased pregnancy complications in polycystic ovary syndrome may be mediated by problems with uterine SpA remodeling, placental functionality, and placental senescence.
Topics: Humans; Rats; Pregnancy; Female; Animals; Placenta; Polycystic Ovary Syndrome; Hyperandrogenism; Uterus; Arteries; Dihydrotestosterone; Insulin; Uterine Artery
PubMed: 37689383
DOI: 10.1016/j.ajpath.2023.08.008 -
Maturitas Oct 2021This narrative review discusses the current understanding, knowledge gaps and challenges in expanding our knowledge of the association between menopause and the... (Review)
Review
This narrative review discusses the current understanding, knowledge gaps and challenges in expanding our knowledge of the association between menopause and the reproductive aging process and cardiometabolic disease (CMD) in women, with a focus on type 2 diabetes and cardiovascular disease. The physiological changes that occur at different stages of the reproductive life span, as well as type of menopause and timing, are factors widely associated with CMD risk; however, the underlying mechanisms remain either unclear or insufficiently studied. Decreased ovarian estrogen production and relative androgen excess around menopause onset are the most studied factors linking menopause and cardiometabolic health; nevertheless, the evidence is not persuasive and other hypotheses might explain the changes in CMD risk during menopausal transition. In this context, hormone therapy has been widely adopted in the treatment and prevention of CMD, although uncertainty regarding its cardiometabolic effects has raised the need to optimize therapeutic modalities. Mechanisms such as the "iron overload theory" and new "omics" platforms could provide new insights into potential pathways underlying the association between menopause and cardiometabolic health, such as the DNA damage response. Although it has been widely reported that environmental and lifestyle factors affect both menopause and cardiometabolic health, there is little evidence on the role of these exposures in menopause-associated CMD risk.
Topics: Aging; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Menopause; Reproduction; Women's Health
PubMed: 34674807
DOI: 10.1016/j.maturitas.2021.06.013 -
Frontiers in Endocrinology 2023Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies.
BACKGROUND
Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies.
METHODS
We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates.
RESULTS
The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031).
CONCLUSION
Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.
Topics: Female; Humans; Endometrial Neoplasms; Endometriosis; Genital Diseases, Female; Genome-Wide Association Study; Mendelian Randomization Analysis; Menopause, Premature; Ovarian Neoplasms; Polycystic Ovary Syndrome; Primary Ovarian Insufficiency; Testosterone
PubMed: 38075074
DOI: 10.3389/fendo.2023.1161356 -
Women's Health (London, England) Mar 2015Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Unfortunately, there are many deficiencies in... (Review)
Review
Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound physical and psychological consequences. Unfortunately, there are many deficiencies in our understanding of the condition as the underlying etiology and optimum management strategies are poorly understood. Improved awareness of POI and its long-term implications has led to increased research interest in recent years. Current research has allowed a greater understanding of the changing epidemiology in POI, genetic factors in its etiology and randomized controlled trials of hormone therapy are underway to provide evidence for treatment. This article reviews the latest literature on POI to summarize current understanding and future directions.
Topics: Age Factors; Androgens; Body Image; Chromosomes, Human, X; Diagnosis, Differential; Female; Hormone Replacement Therapy; Humans; Infections; Infertility, Female; Mental Health; Ovarian Reserve; Primary Ovarian Insufficiency; Quality of Life; Sexual Dysfunction, Physiological; Women's Health
PubMed: 25776291
DOI: 10.2217/whe.14.82 -
Nutrients Aug 2022(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism...
(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism on conservative and hemodialysis treatment. (Methods) The studied population consisted of 38 men on hemodialysis (HD), 46 men with CKD stages II-IV (predialysis group, PreD) and 35 men without kidney disease who were similar in age to others (control group). Serum total testosterone level (TT) was measured, and free testosterone level (fT) was calculated. Hypogonadism criteria according to the EAU definition were fulfilled by 26 men on HD (68.4%) and by 24 men from the PreD group (52%). Testosterone replacement therapy (TRT) with testosterone enanthate in intramuscular injections every 3 weeks was applied in 15 men from HD and in 14 men from PreD. The safety of TRT was monitored by measuring PSA and overhydration. (Results) A significant rise of TT and fT was observed after 3 months of TRT, but no significant changes were observed after 6 and 12 months in the HD and PreD group. An intensity of clinical symptoms of hypogonadism measured by ADAM (androgen deficiency in the ageing male) questionnaire gradually decreased, and the intensity of erectile dysfunction measured by the IIEF-5 (international index of erectile functioning) questionnaire also decreased after 3, 6 and 12 months of TRT in the HD and PreD group. (Conclusions) The applied model of TRT is effective in the correction of clinical signs of hypogonadism without a significant risk of overhydration or PSA changes.
Topics: Hormone Replacement Therapy; Humans; Hypogonadism; Male; Prostate-Specific Antigen; Renal Insufficiency, Chronic; Testosterone
PubMed: 36014950
DOI: 10.3390/nu14163444 -
Endocrinology and Metabolism Clinics of... Jun 2015Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of... (Review)
Review
Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids (primarily aldosterone), glucocorticoids (primarily cortisol), and adrenal androgens (primarily dehydroepiandrosterone and its sulfate) occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal-recessive enzymatic defects in cortisol biosynthesis. 21-Hydroxylase (21OHD) deficiency accounts for more than 90% of CAH cases and, when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases.
Topics: Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocortical Adenoma; Aldosterone; Androgens; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Mineralocorticoids; Myelolipoma; Risk Factors
PubMed: 26038201
DOI: 10.1016/j.ecl.2015.02.002