Elevated Sex Hormone-binding Globulin Research Articles

Genetic and observational evidence supports a causal role of sex hormones on the development of asthma

IntroductionMales have a higher prevalence of asthma in childhood, whereas females have a higher prevalence in adolescence and adulthood. The ‘adolescent switch’ observed between sexes during puberty has been hypothesised...

Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance.

Hepatitis C virus (HCV) and hepatic dysfunction are associated with low total and free testosterone (TT and FT) and high sex hormone-binding globulin (SHBG). However, little is known about changes in testosterone following successful HCV treatment. We evaluated testosterone levels and the prevalence of low testosterone in a cohort of 327 men with chronic HCV infection (human immunodeficiency virus [HIV] coinfection = 150) and in a subset of 85 men with testosterone levels obtained pre-HCV treatment and after sustained virologic response (SVR). Median follow-up was 36 months. Participants with active HCV at baseline had higher TT (P < .0001) and SHBG (P < .0001) compared with participants who had achieved SVR, whereas FT did not differ. Low TT (<10.4 nmol/L) was more prevalent in participants with SVR compared with active HCV (P = .002); however, low FT (<0.1735 nmol/L) was common (50% active HCV, 43% SVR) and did not different between groups. For participants with longitudinal determinations, TT and SHBG decreased significantly (P < .0001) while FT remained unchanged post-SVR. Low FT persisted after SVR (pre-treatment 58%, post-SVR 54%, P = .72). HIV status and change in aspartate aminotrasferase-to-platelet ratio were significant independent predictors of change in FT following SVR. During active HCV infection, testosterone deficiency may be masked due to elevated SHBG. Despite improvements in SHBG following SVR, low FT was common and persisted after HCV clearance, indicating the need for enhanced awareness and screening using estimates of FT following successful treatment of chronic HCV. NCT01350648.

Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS)

Semen quality may be adversely affected by exposure to environmental chemicals such as polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances (PFASs) that are persistent and may act as endocrine disrupting compounds. The aim of this study was to explore whether PCBs or PFASs exposure were associated with abnormalities in semen quality or reproductive hormones in Faroese men. This population based cross-sectional study includes 263 Faroese men (24–26 years) who delivered a semen sample for assessment of sperm concentration, total sperm count, semen volume, morphology and motility. A blood sample was drawn and analyzed for reproductive hormones, PCBs and PFASs. Exposure to ∑PCBs and perfluorooctane sulfonate (PFOS) was positively associated with sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). In addition, total testosterone (T) was positively associated with ∑PCB. Both PCBs and PFOS appear to lead to increased SHBG, perhaps mediated via the liver. The higher total T associated with PCB may represent a compensatory adaption to elevated SHBG levels to maintain an unchanged free testosterone concentration. The positive association to LH for both PCBs and PFOS may indicate a direct adverse effect on the testosterone producing Leydig cells.

Are the estrogenic hormonal effects of environmental toxins affecting small intestinal bacterial and microfilaria overgrowth?

The important role of microfilaria (worms) in human and animal disease remains an area of key disagreement between the naturopathic and allopathic physicians. While microfilaria infections are rampart in undeveloped countries, they rarely rise to identification as a cause of disease in Western countries. New research studies in the diagnosis and treatment of SIBO (Small Intestinal Bacterial Overgrowth) and (IBD) Inflammatory Bowel Diseases of ulcerative colitis, Crohn’s Disease and microcytic colitis may make both sides equally correct. A study of rifaximin failures in SIBO positive individuals finds biomarkers of decreased Free Androgen Index (FAI), high incidence of autoimmune disease and elevated Sex Hormone Binding Globulin (SHBG). The author hypothesizes that the underlying pathophysiology is increased exposure to Endocrine Disrupting Chemicals (EDCs) which hormonally act as xeno-estrogens. These xeno-estrogens increase the host production of SHBG, reduce pituitary stimulation of androgen product and result in a shift to estrogen dominance. Estrogen dominance is associated with autoimmune diseases and catabolic states. Treatment with a mixture of anabolic steroids that raises the FAI and lowers SHBG results in dramatic improvement in the signs and symptoms and recovery of the vast percentage of severe SIBO sufferers the author has treated. Similar results have been seen in severe pre-surgical cases of IBD whom fail all pharmaceutical interventions. Based on the recent recognition of the biological importance of Wolbachia in the occurrence of major diseases in the underdeveloped countries such as onchocerciasis, and the sexual nature of Wolbachia’s role in helminths reproduction, the author hypothesizes that the EDCs are shifting the host’s hormonal milieu in a more estrogenic direction and increasing reproduction of helminths changing the gastrointestinal microbiota. Present allopathic treatment of onchocerciasis utilizes albendazole and avermectin as therapy against the microfilaria larvae and doxycycline as bactericidal for Wolbachia. The allopathic treatments are unacceptable for pregnancy and children. Both naturopathic and allopathic treatments share a common focus on the suppression of the underlying bacterium Wolbachia infestation. The author hypothesizes that treatment of these two very different gastrointestinal diseases involves first establishing a normal, anabolic hormonal milieu and concurrently controlling an underlying yet unrecognized microfilaria overgrowth through naturopathic and allopathic treatments prescribed to the host. A case report of one such critically ill individual is noted. A thorough case controlled observation of symptoms matched with biological culture colony count and concentration of microfilaria in disease before and after the aforementioned anabolic treatment may answer the hypothesis.

Sex difference determined the role of sex hormone-binding globulin in obese children during short-term weight reduction program.

The relationship between hyperinsulinemia and decreased sex hormone-binding globulin (SHBG) levels has been observed in obese adults and children. Weight reduction not only increased insulin sensitivity but also elevated serum SHBG levels in obese adults and children. However, the correlation between the changes in insulin resistance indices and serum SHBG concentration during weight reduction program (WRP) is not fully understood, particularly in obese children. This study is to evaluate whether SHBG level is a potential biomarker that can be used to assess insulin resistance in obese children during a short-term WRP. Forty-eight obese Taiwanese children (11.7 ± 2.2 years; 25 boys and 23 girls) participating in 8-week WRP were studied. Anthropometric measurements, lipid profiles, insulin resistance indices, and serum SHBG concentration were recorded at baseline and at the end of the WRP. The results showed body weight (BW), body mass index (BMI), body fat percentage (BF%), body fat weight (BFW), and insulin resistance indices such as fasting insulin, fasting insulin to glucose ratio, homeostasis model assessment (HOMA) of insulin resistance, log (HOMA) all significantly decreased after the 8-week WRP. With respect to lipid profiles, only high-density lipoprotein cholesterol (HDL-C) levels increased in both sexes. At baseline, insulin resistance indices were inversely correlated with SHBG concentrations in girls, but not in boys. The difference in SHBG after WRP was 2.58 nmol/L (95% confidence interval [CI]: −3.51, 8.66) in boys and 0.58 nmol/L (95% CI: −5.23, 6.39) in girls. There was a trend toward increased serum SHBG levels in boys (P = .39) and girls (P = .84) after weight loss, but a significantly negative correlation between the change in SHBG and in each of the insulin resistance indices only in the girls after adjusting age and ΔBFW during WRP.In conclusion, short-term WRP has the potential effects of decreased BW, BMI, BF%, and BFW, as well as increased serum HDL-C levels and insulin sensitivity in obese Taiwanese children. Although serum SHBG levels moderately increased in both sexes during short-term WRP, measuring the change in SHBG concentrations might be a potential biomarker to evaluate improvement in insulin resistance in girls only, and not in boys.

5-alpha Reductase Deficiency in Two Siblings: A Case Report

A deficiency of 5-alpha reductase is a rare genetic disorder that affects 46,XY patients. The lack of enzyme causes inadequate differentiation of the gonads, leading to ambiguous genitalia or complete feminization of the external genitalia. Two sisters presented to their endocrinologist complaining of primary amenorrhea. Molecular studies revealed the SRD5A2 His231Arg gene mutation and karyotype showed 46,XY genotype. The diagnosis was supported by their high testosterone/dihydrotestosterone (DHT) ratio, response to the hCG stimulation test and their elevated sex hormone binding globulin (SHBG) levels. The siblings continued to identify as the female gender and were placed on oral premarin to develop secondary female sexual characteristics. In conclusion, any individual presenting with ambiguous genitalia, primary amenorrhea or virilization should be investigated for 5-alpha reductase deficiency by conducting a karyotype and full hormone profile. J Med Cases. 2016;7(7):263-265 doi: http://dx.doi.org/10.14740/jmc2482w

5-α Reductase Deficiency in Two Siblings: A Case Report

A deficiency of 5-alpha reductase is a rare genetic disorder that affects 46,XY patients. The lack of enzyme causes inadequate differentiation of the gonads, leading to ambiguous genitalia or complete feminization of the external genitalia. Two sisters presented to their endocrinologist complaining of primary amenorrhea. Molecular studies revealed the SRD5A2 His231Arg gene mutation and karyotype showed 46,XY genotype. The diagnosis was supported by their high testosterone/dihydrotestosterone (DHT) ratio, response to the hCG stimulation test and their elevated sex hormone binding globulin (SHBG) levels. The siblings continued to identify as the female gender and were placed on oral premarin to develop secondary female sexual characteristics. In conclusion, any individual presenting with ambiguous genitalia, primary amenorrhea or virilization should be investigated for 5-alpha reductase deficiency by conducting a karyotype and full hormone profile. J Med Cases. 2016;7(7):263-265 doi: http://dx.doi.org/10.14740/jmc2482w

Exposure to bisphenol-A and reproductive hormones among male adults

BackgroundBisphenol A (BPA) is a suspected human endocrine disruptor which is widely used. MethodsIn order to determine whether urine BPA level is associated with serum reproductive hormone levels among male adults, we carried out a cross-sectional study in China. We recruited 592 male workers and collected their urine samples for BPA measurement. We also collected blood samples and examined serum reproductive hormones. We used multiple linear regression and log-binomial model to examine associations between urine BPA level and hormone levels after controlling for age and smoking status. ResultsAn increased urine BPA level was associated with increased prolactin (p<0.001), estradiol (p<0.001), sex hormone-binding globulin level (p=0.001), and a reduced androstenedione (p<0.001) and free androgen index level (p=0.021). Males, whose urine BPA level was in the 2nd, 3rd and highest quartiles, had respectively 1.58, 1.33 and 3.09-fold increased prevalence of having a high prolactin level (>P75 level). The highest quartile of BPA level was associated with 1.63 and 1.50-fold increased prevalence of having a high estradiol and elevated sex hormone-binding globulin level. Males with higher quartile of BPA level had a lower inhibin B level. ConclusionHigh BPA exposure is associated with increased prolactin, estradiol and sex hormone-binding globulin level in males, and may contribute to male infertility.

Erectile dysfunction with elevated serum testosterone

Symptoms of testosterone deficiency with elevated testosterone levels are rare and could occur with elevated sex hormone binding globulin (SHBG) levels. Here, we report a 59 year old patient presenting with erectile dysfunction (ED) with diminished libido for 4 months. He developed these symptoms 6 months after starting anti tuberculosis treatment (AAT). He had elevated total testosterone concentration along with raised SHBG. However, his free testosterone was normal. Repeated total testosterone level 2 months after completion of ATT was normal indicating normalization of SHBG levels.

The gonadotrophic response of Royal Marines during an operational deployment in Afghanistan.

Military training has been associated with changes in the hypothalamic-pituitary-gonadal axis consistent with central hypogonadism. Often such changes have been associated with body mass loss, though sleep deprivation and other psychological stress may also contribute. The effects of deployment in a combat zone on the hypothalamic-pituitary-gonadal axis in military personnel are not known. The objective was to investigate the hypothalamic-pituitary-gonadal axis in male military personnel deployed in Afghanistan. Eighty-nine Royal Marines were investigated pre-deployment, following 3 months in Afghanistan and following 2 weeks mid-tour leave. Testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinising hormone (LH), 17-hydroxyprogesterone, androstenedione (AD) and insulin were assayed and body mass recorded. The results showed that body mass (kg) dropped from 83.2 ± 9.2 to 79.2 ± 8.2 kg during the first 3 months of deployment (p < 0.001). Total testosterone did not change, but SHBG increased (30.7 ± 9.7 vs. 42.3 ± 14.1 nmol/L, p < 0.001), resulting in a significant (p < 0.001) fall in calculated free testosterone (435.2 ± 138 vs. 375.1 ± 98 pmol/L). Luteinising hormone and FSH increased by 14.3% (p < 0.001) and 4.9% (p = 0.003) respectively. Free testosterone, SHBG, LH and FSH returned to baseline following 2 weeks of mid-tour leave. Androstenedione (AD) decreased by 14.5% (p = 0.024), and insulin decreased by 26% (p = 0.039), over the course of deployment. In this study of lean Royal Marines, free testosterone decreased during operational deployment to Afghanistan. There was no evidence to suggest major stress-induced central hypogonadism. We postulate that reduced body mass, accompanied by a decrease in insulin and AD synthesis, may have contributed to an elevated SHBG, leading to a decrease in free testosterone.

Free Testosterone for Hypogonadism Assessment in HIV-Infected Men

To the Editor—We read with interest the updated human immunodeficiency virus (HIV) primary care guidelines by Aberg et al in Clinical Infectious Diseases on 1 January 2014 [1] and would like to bring an additional comment to readers' attention. We agree with the authors that the preferred initial assay for hypogonadism diagnosis in HIV-infected men has not been definitively established, although experts in the field have advocated using morning free testosterone (FT) as the initial assay in HIV-infected men for 10 years [2]. HIV-infected men have elevated sex hormone binding globulin levels, which can make total testosterone (TT) appear normal even in the setting of inadequate testosterone production [3]. Clinical data supporting the use of morning FT for initial diagnosis of hypogonadism in HIV-infected men have been sparse. Therefore, we recently performed an analysis using data from the Multicenter AIDS Cohort Study [4]. Data were analyzed from >500 HIV-infected and -uninfected men not on testosterone replacement therapy in whom morning TT and FT levels were available. Biochemical hypogonadism (FT <50 pg/mL or TT <300 ng/dL) was present in 7.2% of HIV-uninfected men and 9.3% of HIV-infected men. Of the men with biochemical hypogonadism (n = 46), 11 of 34 of the HIV-infected men had normal TT but low FT. In contrast, all of the HIV-uninfected men had both low TT and low FT. The implication of our finding is that if morning TT alone were used as the initial diagnostic test for hypogonadism in HIV-infected men, one-third of the men would be missed. We also examined characteristics of the HIV-infected men who had normal TT but low FT compared with those who had both low TT and low FT. Hepatitis C virus (HCV) infection was significantly associated with having normal TT but low FT. Therefore, HIV/HCV-coinfected patients may be particularly likely to be missed if TT is used. For these reasons, we suggest using morning FT as the initial diagnostic test for hypogonadism in HIV-infected men to improve diagnostic sensitivity.

Oleic acid increases hepatic sex hormone binding globulin production in men

Low circulating sex hormone-binding globulin (SHBG) is an independent risk factor for cardiovascular disease. Mediterranean diet has been associated with a decreased risk of cardiovascular disease. We aimed to test the hypothesis that the increase of circulating MUFA associated with olive oil consumption (primary fat source in Mediterranean diet) increases SHBG serum levels. A total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003). In the multiple regression analysis, MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance. In vitro studies revealed that oleoyl-CoA increases SHBG production by downregulating PPAR-γ levels in HepG2 cells. Olive oil consumption is associated with elevated SHBG serum levels. PPAR-γ downregulation induced by oleoyl-CoA is an important underlying mechanism of such regulation.

Sex hormone‐binding globulin levels are not causally related to venous thrombosis risk in women not using hormonal contraceptives

Oral contraceptive use increases the risk of venous thrombosis as well as sex hormone-binding globulin (SHBG) levels. Furthermore, increased SHBG levels are positively associated with activated protein C (APC) resistance and thrombotic risk in oral contraceptive users. To determine whether increased SHBG levels are causally related to venous thrombosis in women not using hormonal contraceptives. Premenopausal women were selected from a case-control study on venous thrombosis, the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study (23 patients; 258 controls). Women using hormonal contraceptives were excluded. First, the risk of venous thrombosis with SHBG levels above the normal reference range (70 nm) was determined. Second, because multiple regulatory factors affect SHBG levels and residual confounding may remain, we determined six single-nucleotide polymorphisms (SNPs) in the SHBG gene and assessed the risk of venous thrombosis in a different case-control study, the Leiden Thrombophilia Study (LETS) (20 patients; 74 controls), and in the MEGA study. Finally, the association between SHBG levels and the normalized activated partial thromboplastin time-based APC resistance (an intermediate endpoint for venous thrombosis) was determined. Elevated SHBG levels (> 70.0 nm) were associated with venous thrombosis (odds ratio 1.92; 95% confidence interval [CI] 0.74-5.00). However, this finding can be explained by residual confounding. Two SNPs in the SHBG gene affected SHBG levels, but not venous thrombosis risk. Furthermore, SHBG levels in controls were not associated with APC resistance (SHBG level, > 70.0 vs. ≤ 70.0 nm: mean difference in normalized APC sensitivity ratio, 0.03; 95% CI -0.05 to 0.10). Exclusion of women with FV Leiden did not materially change these results. Increased SHBG levels are not causally related to the risk of venous thrombosis.

Variants in CYP17 and CYP19 Cytochrome P450 Genes are Associated with Onset of Alzheimer's Disease in Women with Down Syndrome

CYP17 and CYP19 are involved in the peripheral synthesis of estrogens, and polymorphisms in CYP17 and CYP19 have been associated with increased risk of estrogen-related disorders. Women with Down syndrome (DS) have early onset and high risk for Alzheimer's disease (AD). We conducted a prospective community-based cohort study to examine the relationship between SNPs in CYP17 and CYP19 and cumulative incidence of AD, hormone levels and sex hormone binding globulin in women with DS. Two hundred and thirty-five women with DS, 31 to 67 years of age and nondemented at initial examination, were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health status at 14-20 month intervals over five assessment cycles. We genotyped these individuals for single-nucleotide polymorphisms (SNPs) in CYP17 and CYP19. Four SNPs in CYP17 were associated with a two and one half-fold increased risk of AD, independent of APOE genotype. Four SNPs in CYP19 were associated with a two-fold increased risk of AD, although three were significant only in those without an APOE ε4 allele. Further, carrying high risk alleles in both CYP17 and CYP19 was associated with an almost four-fold increased risk of AD (OR = 3.8, 95% CI, 1.6-9.5) and elevated sex hormone binding globulin in postmenopausal women. The main effect of the CYP17 and CYP19 variants was to decrease the age at onset. These findings suggest that genes contributing to estrogen bioavailability influence risk of AD in women with DS.

An Old Problem with a New Cause-5 Alpha Reductase Inhibitors and Persistent Sexual Dysfunction

This again? Iatrogenic sexual dysfunction I find myself repeating messages because they need to be restated. Perhaps if we all say this loud enough and often enough, others will hear us and learn. How often has someone in The Journal of Sexual Medicine (JSM) written about iatrogenic sexual health problems? How can we ensure that patients will eventually be provided what is needed to make informed decisions about medications or procedures? Despite peer reviewed published reports, the non‐sexual medicine healthcare community often ignores this message. How do we go about ensuring that sexual health will not be dismissed even if the bothersome, frustrating, and embarrassing iatrogenic sexual health problem persists after the treatment is stopped? We in the sexual medicine field, readers of the JSM, know that a hysterectomy can result in better sexual function for some women but with worsened persistent and life‐long sexual dysfunction in others [1,2]. We in the sexual medicine field are aware that hormonal contraception use can result in improved sexual function for some women based on the freedom from contraceptive concerns and control of menstruation. For others, however, hormonal contraception use can precipitate worsening sexual function [3,4] in association with elevated sex hormone binding globulin levels and lowered calculated free testosterone values. In many such women, discontinuation of the hormonal contraception does not result in discontinuation of the sexual health problem. Instead, the biochemical and hormonal problems appear to be long acting and persistent [5].

Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis

To assess the relation between moderate iron overload on sex hormone binding globulin (SHBG) levels and gonadotroph function in men with dysmetabolic iron overload syndrome and the effects of phlebotomy. The relationship between magnetic resonance imaging assessed liver iron concentration (LIC) and plasma ferritin levels with total testosterone, bioavailable testosterone (BT), SHBG and LH levels, were studied in 50 men with moderate dysmetabolic iron excess, in the absence of genetic haemochromatosis, who were randomised to phlebotomy therapy or to normal care. Four patients (8%) had low total testosterone (<10.4 nmol/l) and 13 patients (26%) had low BT (<2.5 nmol/l). In the entire population, those with LIC above the median (90 μmol/l) had a higher mean SHBG (P=0.028), lower LH (P=0.039) than those with LIC below the median. In multivariable analysis (adjusted for age, and fasting insulin) LIC was significantly associated with SHBG (positively) and LH (negatively). Patients in the highest quartile of SHBG had higher LIC (P=0.010) and higher ferritinaemia (P=0.012) than those in the three other quartiles. Iron depletion by venesection did not significantly improve any hormonal levels. Hypogonadism is not infrequent in men with dysmetabolic iron overload syndrome. Liver iron excess is associated with increased plasma SHBG and moderate hypogonadotrophic hypogonadism. Phlebotomy therapy needs further investigation in symptomatic hypogonadal men with dysmetabolic iron excess.

Phenotype and metabolic profile of South Asian women with polycystic ovary syndrome (PCOS): results of a large database from a specialist Endocrine Clinic

Compared with other populations, South Asians have a greater propensity to insulin resistance and the metabolic syndrome (MetS). This is the first study to determine the distribution of phenotypes of polycystic ovary syndrome (PCOS) and their relationship to the MetS among indigenous South Asians. An evaluation of the phenotype and metabolic characteristics of PCOS was conducted by recruiting consecutive women diagnosed by Rotterdam consensus criteria from an Endocrine clinic in Colombo, Sri Lanka. Prevalence of MetS was determined, in relation to the phenotypic subgroup of PCOS and compared with ethnically matched, BMI- and age-adjusted controls (n =231). Acanthosis nigricans (AN) occurred in 64.6% of women with PCOS (n= 469). MetS occurred in 30.6% of the PCOS group compared with 6.34% of controls (P = 0.0001). Those with PCOS and MetS had significantly higher median BMI, blood pressure (BP), fasting plasma glucose, insulin and triglycerides and lower high-density lipoprotein and sex hormone-binding globulin (SHBG), but similar testosterone concentrations compared with those with PCOS alone. Prevalence of MetS was similar in the four PCOS phenotypes, although oligomenorrhoeic women were more obese compared with the normal cycling hyperandrogenic group. Multivariate logistic regression confirmed age ≥35 years, BMI ≥25 kg/m(2) and AN as significant predictors of MetS in PCOS. Case-control comparisons showed that the presence of PCOS results in higher odds of having the MetS, a high waist circumference, elevated diastolic BP, abnormal fasting lipids and high fasting insulin and plasma testosterone concentrations. Young indigenous South Asians with PCOS have greater odds of being centrally obese, with a third having the MetS that bears no relationship to the androgenic phenotype. Significant predictors for MetS within the PCOS cohort are advancing age, obesity determined by the Asian cut off (BMI >25 kg/m(2)) and AN, while family history of diabetes, hyperandrogenism and elevated SHBG have no predictive value.

Infertility in women with epilepsy

Studies suggest that women with epilepsy (WWE) have reduced fertility rates when compared to the general population. Wallace and colleagues,1 using the General Practice Research Database in the United Kingdom, reported that fertility rates among women with epilepsy were 33% lower than in women in the general population. Not all studies have demonstrated such findings, however. In their population-based study in Iceland, Olafsson and colleagues2 found no evidence of reduced fertility in WWE. All previously published studies assessing fertility rates in WWE are retrospective. Potential contributing factors to reduced fertility in WWE include lower marriage rates, reproductive endocrine dysfunction secondary to antiepileptic (AED) drug exposure and seizure type, fear of malformations secondary to AED exposure, concern of increased risk of epilepsy in offspring, and social stigmatization of epilepsy.1,3 AEDs may influence fertility. Enzyme-inducing AEDs are known to affect concentrations of sex steroid hormones and sex hormone binding globulin. Reduced sex steroid hormones and elevated sex hormone binding globulin together reduce the bioavailability of reproductive …

Metformin influence on hormone levels at birth, in PCOS mothers and their newborns

Polycystic ovary syndrome (PCOS) tends to run in families and excess intrauterine androgen exposure has been suggested as one possible cause of PCOS. We wanted to study the relationship between maternal and offspring sex hormone levels and the possible effects of metformin treatment in PCOS pregnancies. We performed a post hoc analysis of a trial in which 40 pregnant women with PCOS were randomized in the first trimester, to use either metformin 850 mg twice daily or placebo until delivery. Maternal venous blood and umbilical arterial and venous blood samples were collected at delivery. Outcome measures were levels of androgens, estrogens and sex hormone binding globulin (SHBG). (i) In newborns, SHBG levels were higher in the metformin group. All other hormones, both in mothers and offspring, were unaffected by metformin treatment. (ii) Mothers, who gave birth to boys, had higher estrone and estradiol levels compared with those who gave birth to girls. (iii) Male newborns had higher levels of testosterone, androstanediol glucuronide and estradiol compared with females. (iv) Positive correlations were found between maternal and newborn levels of androstenedione, dihydrotestosterone and estradiol. Intrauterine metformin exposure seems to result in elevated SHBG levels in newborns. However, at birth, maternal and newborn androgen and estrogen levels are unaffected by metformin use in pregnancy. Although androgen and estrogen levels are higher in male newborns compared with females, maternal and newborn androgen and estrogen levels are highly correlated at birth.

Elevated Sex Hormone Binding Globulin Levels May Contribute to Sexual Dysfunction in Men With Chronic Hepatitis C Virus Infection

Divisions of *Endocrinology ‡Gastroenterology, VA New York Harbor Healthcare System †NYU School of Medicine New York, NY The authors declare no conflict of interest. The authors confirm that there is no financial arrangement with Ballard Medical Products, USA; KeyMed, UK; or SPSS Inc, USA.