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Endocrine Journal Oct 2023Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the... (Review)
Review
Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the needs of the individual patient. Insufficient glucocorticoid treatment will cause adrenal insufficiency, including life-threatening adrenal crisis, while excess of androgen could cause precocious pubertal growth in children, virilization in female patients, and infertility in male and female adult patients. Meanwhile, overtreatment with glucocorticoids causes iatrogenic Cushing's syndrome which could result in growth impairment, obesity, osteoporosis, and hypertension. The dilemma of 21OHD treatment is that glucocorticoid supplementation therapy at physiological dosage does not sufficiently suppress ACTH, consequently leading to adrenal androgen excess. Accordingly, the window for the appropriate glucocorticoid treatment would have to be substantially narrower than that of other types of adrenal insufficiency without androgen excess, such as adrenal hypoplasia. For the appropriate management of classic 21OHD, the physician has to be well versed in the physiology of the adrenal cortex, growth, and reproductive function. Comprehensive understanding of patients' requirements according to their life stage and sex is essential. Furthermore, female patients with 46,XX need to be cared for as differences in sex development (DSD) with careful psychological management. In this review, we aimed to comprehensively summarize the current status of classic 21OHD treatment, including the initial treatment during the neonatal period, management of adrenal insufficiency, maintenance therapy of each life stage, and the importance of clinical management as DSD for 46,XX female patients. The recently developed agents, Chronocort, and Crinecerfont, are also discussed.
Topics: Adult; Child; Infant, Newborn; Humans; Male; Female; Glucocorticoids; Androgens; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Steroid 21-Hydroxylase
PubMed: 37380491
DOI: 10.1507/endocrj.EJ23-0075 -
Fertility and Sterility Apr 2002To evaluate the evidence for and against androgen insufficiency as a cause of sexual and other health-related problems in women and to make recommendations regarding... (Review)
Review
OBJECTIVE
To evaluate the evidence for and against androgen insufficiency as a cause of sexual and other health-related problems in women and to make recommendations regarding definition, diagnosis, and assessment of androgen deficiency states in women.
DESIGN
Evaluation of peer-review literature and consensus conference of international experts.
SETTING
Multinational conference in the United States.
PATIENT(S)
Premenopausal and postmenopausal women with androgen deficiency.
INTERVENTION(S)
Evaluation of peer-review literature and development of consensus panel guidelines.
RESULT(S)
The term "female androgen insufficiency" was defined as consisting of a pattern of clinical symptoms in the presence of decreased bioavailable T and normal estrogen status. Currently available assays were found to be lacking in sensitivity and reliability at the lower ranges, and the need for an equilibrium dialysis measure was strongly emphasized. Causes of androgen insufficiency in women were classified as ovarian, adrenal, hypothalamic-pituitary, drug-related, and idiopathic. A simplified management algorithm and clinical guidelines were proposed to assist clinicians in diagnosis and assessment. Androgen replacement is currently available in several forms, although none has been approved for treatment of sexual dysfunction or other common symptoms of female androgen insufficiency. Potential risks associated with treatment were identified, and the need for informed consent and careful monitoring was noted. Finally, the panel identified key goals and priorities for future research.
CONCLUSION(S)
A new definition of androgen insufficiency in women has been proposed along with consensus-based guidelines for clinical assessment and diagnosis. A simplified management algorithm for women with low androgen in the presence of clinical symptoms and normal estrogen status has also been proposed.
Topics: Androgens; Dehydroepiandrosterone Sulfate; Diagnosis, Differential; Female; Health Priorities; Hormone Replacement Therapy; Humans; Research; Sex Hormone-Binding Globulin; Testosterone; Women's Health
PubMed: 11937111
DOI: 10.1016/s0015-0282(02)02969-2 -
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 -
Molecular and Cellular Endocrinology May 2021The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation.... (Review)
Review
The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation. It consists of three histologically distinct and functionally specialized zones. The fetal adrenal forms from mesodermal material and produces predominantly adrenal C steroids from its fetal zone, which involutes after birth. Transition to the adult cortex occurs immediately after birth for the formation of the zona glomerulosa and fasciculata for aldosterone and cortisol production and continues through infancy until the zona reticularis for adrenal androgen production is formed with adrenarche. The development of this indispensable organ is complex and not fully understood. This article gives an overview of recent knowledge gained of adrenal biology from two perspectives: one, from basic science studying adrenal development, zonation and homeostasis; and two, from adrenal disorders identified in persons manifesting with various isolated or syndromic forms of primary adrenal insufficiency.
Topics: Adrenal Insufficiency; Aldosterone; Androgens; Animals; Humans; Hydrocortisone; Zona Glomerulosa; Zona Reticularis
PubMed: 33607267
DOI: 10.1016/j.mce.2021.111206 -
World Journal of Gastroenterology May 2015Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence... (Review)
Review
Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.
Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Animals; Antineoplastic Agents, Hormonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Molecular Targeted Therapy; Neoplasms, Hormone-Dependent; Receptors, Androgen; Risk Factors; Sex Factors; Signal Transduction
PubMed: 26034350
DOI: 10.3748/wjg.v21.i20.6146 -
Andrology Feb 2023Low testosterone levels are frequently present in men with obesity and insulin resistance. Currently available treatment options (testosterone replacement therapy or... (Review)
Review
BACKGROUND
Low testosterone levels are frequently present in men with obesity and insulin resistance. Currently available treatment options (testosterone replacement therapy or lifestyle changes) hold possible risks or are insufficient. Since low testosterone levels are closely related to obesity and type 2 diabetes, treatment modalities for these conditions could result into improvement of testosterone levels.
OBJECTIVES
To summarize the available evidence on the effects of traditional and recent treatment modalities for diabetes mellitus on testosterone levels and androgen-deficiency-related signs and symptoms.
MATERIALS AND METHODS
PubMed was searched from the year 2000 till present using MESH terms: "hypogonadism," "testosterone," "testosterone deficiency," "functional hypogonadism," and the different classes of medications. Studies with observational and experimental designs on humans that evaluated the effect of antidiabetic medications on gonadotropins and testosterone were eligible for inclusion.
RESULTS
Current available data show no or only limited improvement on testosterone levels with the classic antidiabetic drugs. Studies with GLP1-receptor analogues show beneficial effects on both body weight and testosterone levels in men with low testosterone levels and obesity with or without type 2 diabetes. However, data are limited to small and heterogeneous study groups and only few studies report data about impact on androgen-deficiency-related signs and symptoms.
DISCUSSION AND CONCLUSION
With the recent advances in the knowledge of the pathophysiological pathways in obesity, there is an enormous progress in the development of medications for obesity and type 2 diabetes. Newer incretin-based agents have a great potential for the treatment of functional hypogonadism due to obesity since they show promising weight reducing results. However, before the use of GLP1-receptor analogues can be suggested to treat functional hypogonadism, further studies are needed.
Topics: Humans; Male; Androgens; Diabetes Mellitus, Type 2; Eunuchism; Hypoglycemic Agents; Hypogonadism; Obesity; Testosterone
PubMed: 36251281
DOI: 10.1111/andr.13318 -
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 -
Fertility and Sterility Aug 2004Review of literature with regard to androgen replacement therapy in women. (Review)
Review
OBJECTIVE
Review of literature with regard to androgen replacement therapy in women.
DESIGN
Review of the MEDLINE database and references from articles.
CONCLUSIONS
Androgens affect sexual function, bone health, muscle mass, body composition, mood, energy, and the sense of well-being. Androgen insufficiency clearly has been demonstrated in patients with hypopituitarism, adrenalectomy, oophorectomy, and in some women placed on oral estrogen therapy which increases sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable forms of T. Symptoms of androgen insufficiency in women may include a diminished sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder with decreased libido, or decreased sexual receptivity and pleasure that causes a great deal of personal distress. The preponderance of evidence from clinical trials supports the correlation of decreased endogenous androgen levels with these symptoms and alleviation of many of the symptoms with the administration of T or, in some cases, DHEA. There are no Food and Drug Administration-approved androgen preparations on the market for treating androgen insufficiency in women. The safety profile of androgens in doses used for the treatment of hypoactive sexual desire disorder has been excellent with only mild acne and hirsutism being noted in a minority of patients.
Topics: Androgens; Clinical Trials as Topic; Dehydroepiandrosterone; Female; Hormone Replacement Therapy; Humans; MEDLINE; Sexuality
PubMed: 15302268
DOI: 10.1016/j.fertnstert.2003.11.062 -
Endocrine Connections Mar 2018Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders. (Review)
Review
BACKGROUND
Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders.
AIM
The aim of this review was to provide an overview on the effects of vitamin D on polycystic ovary syndrome (PCOS) in women and androgen metabolism in men.
METHODS
We performed a systematic literature search in PubMed for relevant English language publications published from January 2012 until September 2017.
RESULTS AND DISCUSSION
The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues of women and men. In women, vitamin D status has been associated with several features of PCOS. In detail, cross-sectional data suggest a regulatory role of vitamin D in PCOS-related aspects such as ovulatory dysfunction, insulin resistance as well as hyperandrogenism. Moreover, results from randomized controlled trials (RCTs) suggest that vitamin D supplementation may be beneficial for metabolic, endocrine and fertility aspects in PCOS. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels.
CONCLUSION
In summary, vitamin D deficiency is associated with adverse fertility outcomes including PCOS and hypogonadism, but the evidence is insufficient to establish causality. High-quality RCTs are needed to further evaluate the effects of vitamin D supplementation in PCOS women as well as on androgen levels in men.
PubMed: 29449314
DOI: 10.1530/EC-18-0009 -
Fertility and Sterility Apr 2002Critical issues concerning the role of androgens in the physical, sexual, and emotional health of women include the following:1. Which androgens best reflect the... (Review)
Review
Critical issues concerning the role of androgens in the physical, sexual, and emotional health of women include the following:1. Which androgens best reflect the androgen status of women? 2. What form of T should be measured and how? 3. Do T levels fall after menopause? 4. What effect does oophorectomy have on T levels? 5. What is the relationship between T and sexual dysfunction? 6. What constitutes androgen insufficiency syndrome? 7. What conditions are associated with androgen insufficiency? 8. How should a patient with suspected androgen insufficiency be evaluated? 9. Does androgen replacement therapy improve sexual dysfunction? 10. Do androgens enhance the quality of life? 11. Is estrogen and androgen therapy superior to estrogen therapy alone for low bone mineral density? 12. What are the indications for androgen replacement therapy? 13. What is the best means for delivery of androgen therapy? 14. How should androgen replacement therapy be monitored? Based on our current knowledge, it is clear that some women develop symptomatic androgen insufficiency and that androgen replacement therapy has a beneficial effect on libido, sexual satisfaction, quality of life, and bone mineralization. Androgen replacement therapy should be given the same consideration that we give estrogen replacement therapy.
Topics: Androgens; Female; Hormone Replacement Therapy; Humans; Menopause; Osteoporosis; Ovariectomy; Sexual Dysfunction, Physiological; Testosterone
PubMed: 12007911
DOI: 10.1016/s0015-0282(02)02962-x