DOCSLIB.ORG

Sex Hormones, Obesity and Type 2 Diabetes: Is There a Link?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

ID: 18-0450 8 1 A Gambineri and C Pelusi Testosterone, obesity and 8:1 R1–R9 diabetes REVIEW Sex hormones, obesity and type 2 diabetes: is there a link? Alessandra Gambineri and Carla Pelusi Endocrinology Unit, Department of Medical and Surgical Sciences, St Orsola-Malpighi Hospital, Alma Mater University of Bologna, Bologna, Italy Correspondence should be addressed to A Gambineri: [email protected] Abstract An imbalance in sex hormones has an important impact on type 2 diabetes (T2DM) Key Words mainly through the involvement of visceral adipose tissue. Androgens have an f androgens interesting sex-dimorphic association with T2DM, since hyperandrogenism in females f estrogens and hypogonadism in males are risk factors for T2DM. Thus, treatments aimed at f sex correcting hyperandrogenism in females and hypogonadism in males may prevent the f obesity development of T2DM or help in its treatment. f diabetes Endocrine Connections (2019) 8, R1–R9 Role of sex and gender on the development Sex hormone differences between the sexes of type 2 diabetes Males and females produce the same steroid hormones in There is increasing evidence that sex and gender differences a similar way. Regarding androgens, in both sexes, there influence the epidemiology, pathophysiology, treatment are different synthesis pathways; a classic pathway where and outcomes of many diseases, including type 2 diabetes testosterone is synthesized directly in testicular Leydig (T2DM) (1). The term sex is used to primarily indicate cells in men and ovarian theca cells in women. Androgens biological differences and the term gender predominantly are parallel produced from Δ5- and Δ4-precursors, and describes the psychosocial differences between sexes. Sex therefore, converted into peripheral target tissues to differences between women and men include differences in the more potent androgen 5α-dihydrotestosterone sex hormones and their effects on organ systems. Gender (DHT) by 5α-reductase enzyme (3). However, it is also differences arise from sociocultural processes and include possible that testosterone is locally synthesized at the different forms of nutrition, life styles or stress or attitudes level of peripheral organs. For example, at the level of toward treatments and prevention of diseases. Sex and gender the adipose tissue, androstenedione (A4) is converted differences are equally important in terms of development, to testosterone by 17β-hydroxysteroid dehydrogenase awareness, presentation, diagnosis and therapy, as well as type 5 (17β-HSD5) and testosterone may be further the prevention of T2DM, influencing each other, above all activated to DHT by the type 1 isoform of 5α-reductase. through the impact on obesity. There is a general agreement In addition, there are several alternative pathways to DHT that obesity is the major risk factor for T2DM in both sexes, synthesis, the backdoor pathway and alternate 5α-dione as supported by the data of the prevalence patterns of T2DM pathway, which directly synthesize DHT from circulating across regions which resemble those of obesity (2). androgen precursors in peripheral tissues bypassing This review focuses on the link between sex hormones the conventional intermediate testosterone (3). There and T2DM through the impact that a sex hormone is also an 11-oxygenated adrenal androgen pathway imbalance has on metabolic tissues, particularly on which converts A4 to 11β-hydroxyandrostenedione adipose tissue. The sexual dimorphism of androgens in (11OHA4) and testosterone to 11-keto-testosterone the pathophysiology of T2DM is emphasized. (11KT) and 11-keto-dihydrotestosterone (11KDHT) by https://ec.bioscientifica.com © 2019 The authors This work is licensed under a Creative Commons https://doi.org/10.1530/EC-18-0450 Published by Bioscientifica Ltd Attribution-NonCommercial-NoDerivatives 4.0 InternationalDownloaded License. from Bioscientifica.com at 09/23/2021 08:05:29PM via free access -18-0450 PB–R10 A Gambineri and C Pelusi Testosterone, obesity and 8:1 R2 diabetes adrenal 11β-hydroxylase (CYP11B1) activity. These are of E2 and distinct between sexes. In addition, in females, active 11-oxygenated androgens (3). In particular, 11KT the amount of testosterone that is bound to SHBG is and 11KDHT are able to activate the human androgen significantly higher than that in males (77 vs 53%). receptor (AR) with the same potency as testosterone Therefore, changes in the level of SHBG have a greater effect and DHT. A4 and testosterone can be converted to the on the free testosterone level (and thus on its biological estrogens estrone (E1) and estradiol (E2), respectively, expression) than on the corresponding free E2 level, and by aromatase (CYP19A1), which has been found in the this is particularly evident in the free testosterone level of ovary and testis as well as in many extragonadal tissues, females with respect to males. Thus, the serum transport including the brain, prostate gland, breast, bone, muscle, of androgens and estrogens contributes to sex-based liver and adipose tissue. differences by regulating the relative free hormone levels The fact that both sexes make the same steroid available to target tissues. Main sex hormone differences hormones in a similar way means that physiological between the sexes are summarized in Table 1. differences are necessarily quantitative in terms of (i) how much androgen is made, and (ii) what percentage of that quantity is converted into estrogen. If we focus on Sex-dimorphic association between testosterone and E2, the two most potent representatives androgens and type 2 diabetes results from of their classes and the principal hormones synthesized clinical studies in the gonads, two dramatic differences are evident. The testis makes approximately 7000 μg of testosterone per The sex-dimorphic association between testosterone and day and converts one quarter of 1% into E2, whereas T2DM, which is consistently observed across racial and the ovary makes only 300 μg of testosterone per day, but ethnic groups, is particularly evident in clinical studies fully converts half of it into E2. Thus, men make at least (6). There are many cross-sectional population-based 20 times as much testosterone as women do; however, studies that demonstrate that lower levels of testosterone the percentage of testosterone that is converted into E2 in men and higher levels of testosterone in women are in a woman is 200 times that in a man. In both sexes associated with T2DM, while lower levels of SHBG are testosterone induces the estrogen sulfotransferase (EST), associated with T2DM particularly in females (7). Some which inactivates E2 in E2 sulfate (E2-S); therefore, prospective population-based studies thus indicate that the higher the levels of testosterone, the higher the endogenous testosterone may differentially influence the inactivation of E2 in E2 sulfate, thus contributing to risk of T2DM in men and women. Reduced testosterone the quantitative differences in sex steroids between the levels (both total and free) in men are in fact associated sexes (4). with a higher risk of T2DM, whereas higher testosterone However, there is also a qualitative difference between levels (both total and free) as well as lower levels of SHBG the sexes that depends on the production site of E2. In in females are associated with a higher risk of T2DM (8). healthy premenopausal women, E2 is mainly produced by Interestingly, prospective studies performed on the ovaries and functions as a circulating hormone that men demonstrate that the inverse relationship between acts on distant target tissues. In men and postmenopausal testosterone and the risk of diabetes mainly depend on the women, E2 does not function as a circulating hormone; abdominal obesity phenotype. In fact, after adjustment rather, it is synthesized mainly in extragonadal sites and for waist circumference, this relationship drastically acts as a paracrine and intracrine factor (4). attenuates (9). In females, the risk of T2DM increases with Part of the sex hormone differences between the the aggravation of hyperandrogenism (10) and becomes sexes also depends on the sex hormone-binding globulin particularly evident in hyperandrogenic disorders, such as (SHBG), which regulates the biological effect of sex polycystic ovary syndrome (PCOS). steroids (5). Androgens and estrogens are transported in PCOS is the most common hyperandrogenic disorder the blood by proteins, particularly SHBG and albumin in women with a prevalence in European women in the which regulate the access of steroid hormones to their fertile age of around 6–8% (11). Observational cross- target cells. These proteins have different ligand affinities: sectional studies performed on PCOS and included by albumin binds the sex hormones indistinctly and with a Moran et al. in a meta-analysis estimate that the odds low affinity, whereas SHBG binds the sex hormones with of T2DM are four times as high for women with PCOS a high affinity but the affinity to testosterone is twice that compared with controls (12). A subgroup matched https://ec.bioscientifica.com © 2019 The authors This work is licensed under a Creative Commons https://doi.org/10.1530/EC-18-0450 Published by Bioscientifica Ltd Attribution-NonCommercial-NoDerivatives 4.0 InternationalDownloaded License. from Bioscientifica.com at 09/23/2021 08:05:29PM via free access A Gambineri and C Pelusi Testosterone, obesity and 8:1 R3 diabetes Table 1 Main sex hormone differences between the sexes. Sex differences References Testosterone Men make 20 times as much testosterone as women do per day (3) Estradiol (E2) Men convert testosterone into E2 in a percentage that is 200 times (3, 4) lower than a women E2 in men is synthesized in extragonadal sites and functions as a paracrine and intracrine factor E2 in women is mainly synthesized in the ovaries and functions as a circulating hormone Estrogen sulfotransferase (EST) EST is more active in men than in women (4) Sex hormone-binding globulin (SHBG) Testosterone bound to SHBG is lower in men than in women (5) (53% vs 77%) for BMI confirmed that the odds of T2DM were more development of T2DM in PCOS (17).
Recommended publications
  • (12) United States Patent (10) Patent No.: US 7,074,961 B2 Wang Et Al

    (12) United States Patent (10) Patent No.: US 7,074,961 B2 Wang Et Al

    US007074961B2 (12) United States Patent (10) Patent No.: US 7,074,961 B2 Wang et al. (45) Date of Patent: Jul. 11, 2006 (54) ANTIDEPRESSANTS AND THEIR 6.211,171 B1 4/2001 Sawynok et al. ANALOGUES AS LONG-ACTING LOCAL 6,545,057 B1 4/2003 Wang et al. ANESTHETCS AND ANALGESCS 2001/0036943 A1 11/2001 Coe et al. (75) Inventors: Ging Kuo Wang, Westwood, MA (US); FOREIGN PATENT DOCUMENTS Peter Gerner, Weston, MA (US); Donald K. Verrecchia, Winchester, MA CH 534124 A 2, 1973 (US) WO WO95/17903 A1 7, 1995 WO WO95/1818.6 A1 7, 1995 (73) Assignee: The Brigham and Women's Hospital, WO WO 99.59.598 A1 11, 1999 Inc., Boston, MA (US) WO WO O2/060870 A2 8, 2002 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U.S.C. 154(b) by 451 days. Luo et al., Xenobiotica, vol. 25, No. 3, pp. 291-301, 1995.* (21) Appl. No.: 10/117,708 Ehlert et al., The Interaction of Amitriptyline, Doxepin, Imipramine and Their N-Methyl Quaternary Ammonium (22) Filed: Apr. 4, 2002 Derivatives with Subtypes of Muscarinic Receptors in Brain (65) Prior Publication Data and Heart, The Journal of Pharmacology and Experimental Therapeutics, Apr. 1990, vol. 253, No. 1, pp. 13–19. US 2003/00968.05 A1 May 22, 2003 Gerner, P., et al., Anesthesiology (2002) 96:1435–42. Related U.S. Application Dat e pplication Uata Khan, M.A., et al., Anesthesiology (2002) 96:109–16. (63) stripps'965,138, filed on Sep.
  • Sex Hormones Related Ocular Dryness in Breast Cancer Women

    Sex Hormones Related Ocular Dryness in Breast Cancer Women

    Journal of Clinical Medicine Review Sex Hormones Related Ocular Dryness in Breast Cancer Women Antonella Grasso 1, Antonio Di Zazzo 2,* , Giuseppe Giannaccare 3 , Jaemyoung Sung 4 , Takenori Inomata 4 , Kendrick Co Shih 5 , Alessandra Micera 6, Daniele Gaudenzi 2, Sara Spelta 2 , Maria Angela Romeo 7, Paolo Orsaria 1, Marco Coassin 2 and Vittorio Altomare 1 1 Breast Unit, University Campus Bio-Medico, 00128 Rome, Italy; [email protected] (A.G.); [email protected] (P.O.); [email protected] (V.A.) 2 Ophthalmology Operative Complex Unit, University Campus Bio-Medico, 00128 Rome, Italy; [email protected] (D.G.); [email protected] (S.S.); [email protected] (M.C.) 3 Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; [email protected] 4 Department of Ophthalmology, School of Medicine, Juntendo University, 1130033 Tokyo, Japan; [email protected] (J.S.); [email protected] (T.I.) 5 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; [email protected] 6 Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS–Fondazione Bietti, 00198 Rome, Italy; [email protected] 7 School of Medicine, Humanitas University, 20089 Milan, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-06225418893; Fax: +39-9622541456 Abstract: Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hor- mones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical Citation: Grasso, A.; Di Zazzo, A.; manifestation as dry eye disease.
  • Background Briefing Document from the Consortium of Sponsors for The

    Background Briefing Document from the Consortium of Sponsors for The

    BRIEFING BOOK FOR Pediatric Advisory Committee (PAC) Prepared by Alan Rogol, M.D., Ph.D. Prepared for Consortium of Sponsors Meeting Date: April 8th, 2019 TABLE OF CONTENTS LIST OF FIGURES ................................................... ERROR! BOOKMARK NOT DEFINED. LIST OF TABLES ...........................................................................................................................4 1. INTRODUCTION AND BACKGROUND FOR THE MEETING .............................6 1.1. INDICATION AND USAGE .......................................................................................6 2. SPONSOR CONSORTIUM PARTICIPANTS ............................................................6 2.1. TIMELINE FOR SPONSOR ENGAGEMENT FOR PEDIATRIC ADVISORY COMMITTEE (PAC): ............................................................................6 3. BACKGROUND AND RATIONALE .........................................................................7 3.1. INTRODUCTION ........................................................................................................7 3.2. PHYSICAL CHANGES OF PUBERTY ......................................................................7 3.2.1. Boys ..............................................................................................................................7 3.2.2. Growth and Pubertal Development ..............................................................................8 3.3. AGE AT ONSET OF PUBERTY.................................................................................9 3.4.
  • Curriculum Vitae: Daniel J

    Curriculum Vitae: Daniel J

    CURRICULUM VITAE: DANIEL J. WALLACE, M.D., F.A.C.P., M.A.C.R. Up to date as of January 1, 2019 Personal: Address: 8750 Wilshire Blvd, Suite 350 Beverly Hills, CA 90211 Phone: (310) 652-0010 FAX: (310) 360-6219 E mail: [email protected] Education: University of Southern California, 2/67-6/70, BA Medicine, 1971. University of Southern California, 9/70-6/74, M.D, 1974. Postgraduate Training: 7/74-6/75 Medical Intern, Rhode Island (Brown University) Hospital, Providence, RI. 7/75-6/77 Medical Resident, Cedars-Sinai Medical Center, Los Angeles, CA. 7/77-6/79 Rheumatology Fellow, UCLA School of Medicine, Los Angeles, CA. Medical Boards and Licensure: Diplomate, National Board of Medical Examiners, 1975. Board Certified, American Board of Internal Medicine, 1978. Board Certified, Rheumatology subspecialty, 1982. California License: #G-30533. Present Appointments: Medical Director, Wallace Rheumatic Study Center Attune Health Affiliate, Beverly Hills, CA 90211 Attending Physician, Cedars-Sinai Medical Center, Los Angeles, 1979- Clinical Professor of Medicine, David Geffen School of Medicine at UCLA, 1995- Professor of Medicine, Cedars-Sinai Medical Center, 2012- Expert Reviewer, Medical Board of California, 2007- Associate Director, Rheumatology Fellowship Program, Cedars-Sinai Medical Center, 2010- Board of Governors, Cedars-Sinai Medical Center, 2016- Member, Medical Policy Committee, United Rheumatology, 2017- Honorary Appointments: Fellow, American College of Physicians (FACP) Fellow, American College of Rheumatology (FACR)
  • EAU Pocket Guidelines on Male Hypogonadism 2013

    EAU Pocket Guidelines on Male Hypogonadism 2013

    GUIDELINES ON MALE HYPOGONADISM G.R. Dohle (chair), S. Arver, C. Bettocchi, S. Kliesch, M. Punab, W. de Ronde Introduction Male hypogonadism is a clinical syndrome caused by andro- gen deficiency. It may adversely affect multiple organ func- tions and quality of life. Androgens play a crucial role in the development and maintenance of male reproductive and sexual functions. Low levels of circulating androgens can cause disturbances in male sexual development, resulting in congenital abnormalities of the male reproductive tract. Later in life, this may cause reduced fertility, sexual dysfunc- tion, decreased muscle formation and bone mineralisation, disturbances of fat metabolism, and cognitive dysfunction. Testosterone levels decrease as a process of ageing: signs and symptoms caused by this decline can be considered a normal part of ageing. However, low testosterone levels are also associated with several chronic diseases, and sympto- matic patients may benefit from testosterone treatment. Androgen deficiency increases with age; an annual decline in circulating testosterone of 0.4-2.0% has been reported. In middle-aged men, the incidence was found to be 6%. It is more prevalent in older men, in men with obesity, those with co-morbidities, and in men with a poor health status. Aetiology and forms Male hypogonadism can be classified in 4 forms: 1. Primary forms caused by testicular insufficiency. 2. Secondary forms caused by hypothalamic-pituitary dysfunction. 164 Male Hypogonadism 3. Late onset hypogonadism. 4. Male hypogonadism due to androgen receptor insensitivity. The main causes of these different forms of hypogonadism are highlighted in Table 1. The type of hypogonadism has to be differentiated, as this has implications for patient evaluation and treatment and enables identification of patients with associated health problems.
  • Diverse Pathomechanisms Leading to the Breakdown of Cellular Estrogen Surveillance and Breast Cancer Development: New Therapeutic Strategies

    Diverse Pathomechanisms Leading to the Breakdown of Cellular Estrogen Surveillance and Breast Cancer Development: New Therapeutic Strategies

    Journal name: Drug Design, Development and Therapy Article Designation: Review Year: 2014 Volume: 8 Drug Design, Development and Therapy Dovepress Running head verso: Suba Running head recto: Diverse pathomechanisms leading to breast cancer development open access to scientific and medical research DOI: http://dx.doi.org/10.2147/DDDT.S70570 Open Access Full Text Article REVIEW Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies Zsuzsanna Suba Abstract: Recognition of the two main pathologic mechanisms equally leading to breast cancer National Institute of Oncology, development may provide explanations for the apparently controversial results obtained by sexual Budapest, Hungary hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperandrogenism and estrogen deficiency, but during these ongoing pathologic processes, ER defect also develops. Conversely, when estrogen resistance is the onset of hormonal and metabolic disturbances, initial counteraction is For personal use only. hyperestrogenism. Compensatory mechanisms improve the damaged reactivity of ERs; however, their failure leads to secondary insulin resistance. The final stage of both pathologic pathways is the breakdown of estrogen surveillance, leading to breast cancer development. Among pre- menopausal breast cancer cases, insulin resistance is the preponderant initiator of alterations with hyperandrogenism, which is reflected by the majority of studies suggesting a causal role of hyperandrogenism in breast cancer development. In the majority of postmenopausal cases, tumor development may also be initiated by insulin resistance, while hyperandrogenism is typi- cally coupled with elevated estrogen levels within the low postmenopausal hormone range.
  • Testosterone, Myocardial Function, and Mortality

    Testosterone, Myocardial Function, and Mortality

    Heart Failure Reviews https://doi.org/10.1007/s10741-018-9721-0 Testosterone, myocardial function, and mortality Vittorio Emanuele Bianchi1 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The cardiovascular system is particularly sensitive to androgens, but some controversies exist regarding the effect of testosterone on the heart. While among anabolic abusers, cases of sudden cardiac death have been described, recently it was reported that low serum level of testosterone was correlated with increased risk of cardiovascular diseases (CVD) and mortality rate. This review aims to evaluate the effect of testosterone on myocardial tissue function, coronary artery disease (CAD), and death. Low testosterone level is associated with increased incidence of CAD and mortality. Testosterone administration in hypogonadal elderly men and women has a positive effect on cardiovascular function and improved clinical outcomes and survival time. Although at supraphysiologic doses, androgen may have a toxic effect, and at physiological levels, testosterone is safe and exerts a beneficial effect on myocardial function including mechanisms at cellular and mitochondrial level. The interaction with free testosterone and estradiol should be considered. Further studies are necessary to better understand the interaction mechanisms for an optimal androgen therapy in CVD. Keywords Testosterone . Coronary artery disease . Heart failure . Cardiovascular disease . Cardiomyocytes . Cardiac mitochondria . Cardiovascular mortality Introduction essential role [20]. Asymptomatic hypogonadism is observed in men 30–79 years old with an incidence of about 5.6% [21] The effects of testosterone on myocardial function have gen- and is more relevant in aging subjects. In recent years, pre- erated a great deal of discussion in the literature but remain scriptions for testosterone replacement therapy have increased controversial.
  • Hypogonadism in Adolescence 173:1 R15–R24 Review

    Hypogonadism in Adolescence 173:1 R15–R24 Review

    A A Dwyer and others Hypogonadism in adolescence 173:1 R15–R24 Review TRANSITION IN ENDOCRINOLOGY Hypogonadism in adolescence Andrew A Dwyer1,2, Franziska Phan-Hug1,3, Michael Hauschild1,3, Eglantine Elowe-Gruau1,3 and Nelly Pitteloud1,2,3,4 1Center for Endocrinology and Metabolism in Young Adults (CEMjA), 2Endocrinology, Diabetes and Metabolism Correspondence Service and 3Division of Pediatric Endocrinology Diabetology and Obesity, Department of Pediatric Medicine and should be addressed Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland and to N Pitteloud 4Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 7, Email 1005 Lausanne, Switzerland [email protected] Abstract Puberty is a remarkable developmental process with the activation of the hypothalamic–pituitary–gonadal axis culminating in reproductive capacity. It is accompanied by cognitive, psychological, emotional, and sociocultural changes. There is wide variation in the timing of pubertal onset, and this process is affected by genetic and environmental influences. Disrupted puberty (delayed or absent) leading to hypogonadism may be caused by congenital or acquired etiologies and can have significant impact on both physical and psychosocial well-being. While adolescence is a time of growing autonomy and independence, it is also a time of vulnerability and thus, the impact of hypogonadism can have lasting effects. This review highlights the various forms of hypogonadism in adolescence and the clinical challenges in differentiating normal variants of puberty from pathological states. In addition, hormonal treatment, concerns regarding fertility, emotional support, and effective transition to adult care are discussed. European Journal of Endocrinology (2015) 173, R15–R24 European Journal of Endocrinology Introduction Adolescence is generally defined as the transitional phase (FSH)) (1, 2).
  • The Mechanism of Androgen Actions in PCOS Etiology

    The Mechanism of Androgen Actions in PCOS Etiology

    medical sciences Review The Mechanism of Androgen Actions in PCOS Etiology Valentina Rodriguez Paris 1 and Michael J. Bertoldo 1,2,* 1 Fertility and Research Centre, School of Women’s and Children’s Health, University of New South Wales Sydney, NSW 2052, Australia 2 School of Medical Sciences, University of New South Wales Sydney, NSW 2052, Australia * Correspondence: [email protected] Received: 15 June 2019; Accepted: 20 August 2019; Published: 28 August 2019 Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS.
  • Androgen Deficiency Diagnosis and Management

    Androgen Deficiency Diagnosis and Management

    4 Clinical Summary Guide Androgen Deficiency Diagnosis and management Androgen deficiency (AD) * Pituitary disease, thalassaemia, haemochromatosis. • Androgen deficiency is common, affecting 1 in 200 men under ** AD is an uncommon cause of ED. However, all men presenting 60 years with ED should be assessed for AD • The clinical presentation may be subtle and its diagnosis Examination and assessment of clinical features of AD overlooked unless actively considered Pre-pubertal onset – Infancy The GP’s role • Micropenis • GPs are typically the first point of contact for men with • Small testes symptoms of AD • The GP’s role in the management of AD includes clinical Peri-pubertal onset – Adolescence assessment, laboratory investigations, treatment, referral • Late/incomplete sexual and somatic maturation and follow-up • Small testes • Note that it in 2015 the PBS criteria for testosterone • Failure of enlargement of penis and skin of scrotum becoming prescribing changed; the patient must be referred for a thickened/pigmented consultation with an endocrinologist, urologist or member of • Failure of growth of the larynx the Australasian Chapter of Sexual Health Medicine to be eligible for PBS-subsidised testosterone prescriptions • Poor facial, body and pubic hair • Gynecomastia Androgen deficiency and the ageing male • Poor muscle development • Ageing may be associated with a 1% decline per year in serum Post-pubertal onset – Adult total testosterone starting in the late 30s • Regression of some features of virilisation • However, men who
  • Male Hypogonadism: Quick Reference for Residents

    Male Hypogonadism: Quick Reference for Residents

    Male hypogonadism: Quick Reference for Residents Soe Naing, MD, MRCP(UK), FACE Endocrinologist Associate Clinical Professor of Medicine Director of Division of Endocrinology Medical Director of Community Diabetes Care Center UCSF-Fresno Medical Education Program Version: SN/8-21-2017 Male hypogonadism From Harrison's Principles of Internal Medicine, 19e and Up-To-Date accessed on 8-21-2017 Testosterone is FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain that cause hypogonadism. Examples of these disorders include primary hypogonadism because of genetic problems, or damage from chemotherapy or infection (mump orchitis). However, FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging. Some studies reported an increased risk of heart attack, stroke, or death associated with testosterone treatment, while others did not. FDA cautions that prescription testosterone products are approved only for men who have low testosterone levels caused by a medical condition. http://www.fda.gov/Drugs/DrugSafety/ucm436259.htm 2 Hypothalamic-pituitary-testicular axis Schematic representation of the hypothalamic-pituitary- testicular axis. GnRH from the hypothalamus stimulates the gonadotroph cells of the pituitary to secrete LH and FSH. LH stimulates the Leydig cells of the testes to secrete testosterone. The high concentration of testosterone within the testes is essential for spermatogenesis within the seminiferous tubules. FSH stimulates the Sertoli cells within the seminiferous tubules to make inhibin B, which also stimulates spermatogenesis. Testosterone inhibits GnRH secretion, and inhibin B inhibits FSH secretion.
  • BDNF Genotype Modulates Resting Functional Connectivity in Children

    BDNF Genotype Modulates Resting Functional Connectivity in Children

    ORIGINAL RESEARCH ARTICLE published: 24 November 2009 HUMAN NEUROSCIENCE doi: 10.3389/neuro.09.055.2009 BDNF genotype modulates resting functional connectivity in children Moriah E. Thomason1*, Daniel J. Yoo1, Gary H. Glover 2 and Ian H. Gotlib1 1 Department of Psychology, Stanford University, Stanford, CA, USA 2 Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA Edited by: A specifi c polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated Elizabeth D. O’Hare, University of with alterations in brain anatomy and memory; its relevance to the functional connectivity of California at Berkeley, USA brain networks, however, is unclear. Given that altered hippocampal function and structure Reviewed by: Damien Fair, Oregon Health and has been found in adults who carry the methionine (met) allele of the BDNF gene and the Science University, USA molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we Naftali Raz, Wayne State University, examined the association between BDNF gene variants and neural resting connectivity in USA children and adolescents. We observed a reduction in hippocampal and parahippocampal to *Correspondence: cortical connectivity in met-allele carriers within both default-mode and executive networks. Moriah E. Thomason, Department of Psychology, Stanford University, Jordan In contrast, we observed increased connectivity to amygdala, insula and striatal regions in Hall, Bldg. 420, Stanford, met-carriers, within the paralimbic network. Because of the known association between the CA 94305-2130, USA. BDNF gene and neuropsychiatric disorder, this latter fi nding of greater connectivity in circuits e-mail: [email protected] important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest.