Prevalence and risk factors associated with diabetes mellitus among middle-aged women in southern Brazil: a population-based study.

OBJECTIVES: To investigate prevalence and clinical factors associated with diabetes among middle-aged women. METHODS: In this cross-sectional population-based study, clinical and laboratory examinations were collected from 298 women. Participants wore a digital pedometer for 7 days to assess habitual physical activity. Abdominal computed tomography scans were performed to measure total fat area and visceral fat area. RESULTS: Mean age was 57.1 years (SD, 5.4 y); 78.7% of women were postmenopausal. The prevalence of diabetes was 17.1%. Women with diabetes were older (P = 0.02); worked fewer hours per week in the past month (P = 0.04); had an earlier age at menarche (P = 0.03); were more frequently inactive (P = 0.01); had higher body mass index (P = 0.01), higher waist circumference (P < 0.01), higher visceral (P < 0.01), and higher total fat (P < 0.01) but not subcutaneous fat (P = 0.14); and had higher systolic blood pressure (BP) (P < 0.01). There was a prevalence of 19.5% of current smoking, 32.5% of alcohol use, and 16.1% of current hormone therapy use, prevalence similar among the groups of women. There was a higher prevalence of metabolic syndrome (P < 0.01) and statin use (P < 0.01) in women with diabetes. A higher prevalence ratio of diabetes was associated with physical inactivity (prevalence ratio, 2.137; 95% CI, 1.056-4.325; P < 0.03). The odds of having diabetes increased by 12% for each year of earlier menarche and by 1.4% for each millimeter of mercury increase in systolic BP. CONCLUSION: The prevalence of diabetes was 17.1%. Age, physical inactivity, early age at menarche, and systolic BP were independently associated with higher prevalence of diabetes in this unselected population of middle-aged women.

Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline. DESIGN: Systematic review and meta-analysis of the literature. PATIENTS: Women with PCOS and treatment with insulin sensitisers. MEASUREMENTS: Hormonal and clinical outcomes, as well as side effects. RESULTS: Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m2 ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations. CONCLUSIONS: Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.

Potassium levels in women with polycystic ovary syndrome using spironolactone for long-term.

OBJECTIVE: Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term. DESIGN: Single-centre retrospective study. PATIENTS: Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time. MEASUREMENTS: Clinical and hormonal profiles before and during SPL treatment. RESULTS: Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L). CONCLUSIONS: The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.

Estradiol Replacement as a Potential Enhancer of Working Memory and Neuroplasticity in Hypogonadal Trans Women.

INTRODUCTION: The cognitive effects of cross-sex hormone therapy (CSHT) are not well understood. In cisgender individuals, sex hormone therapy can impact neurotransmitter levels and structural anatomy. Similarly, in gender-diverse persons, CSHT has been associated with neural adaptations, such as growth in brain structures resembling those observed in cisgender individuals of the same sex. Hormone-related changes in learning and memory, as seen in menopause, are associated with physiological hypogonadism or a decline in hormones, such as estradiol. The present study examined the effect of estradiol administration in humans on glutamate concentration in brain regions involved in semantic and working memory (i.e., the dorsolateral prefrontal cortex [DLPFC], the posterior hippocampus, and the pregenual anterior cingulate cortex) and its relationship with memory. METHODS: Eighteen trans women (male biological sex assigned at birth) ceased CSHT for 30 days for a washout phase (t1) upon study enrollment to reach a hypogonadal state. Working and semantic memory, cognition, hormonal assays, and brain imaging were assessed. Participants resumed CSHT for 60 days for a replacement phase (t2), after which the same evaluations from t1 were repeated. RESULTS: Estradiol increased among trans women after 60 days of resumed CSHT with significant improvements in semantic memory compared to the hypogonadal phase. Working memory recall was significantly and positively correlated to glutamate in the DLPFC during the reinstatement phase, although the relationship was not moderated by levels of estradiol. DISCUSSION: These results may have clinical implications for the therapeutic effects of estradiol replacement, serving as a protective factor against cognitive decline and impairment for trans women post-gonadectomy.

Impact of vascular liver disease on the menstrual cycle and metabolic status in premenopausal women.

BACKGROUND: Vascular liver disease (VLD) are rare liver diseases, which affect women at reproductive ages. Main complications are bleeding (portal hypertension, thrombopenia or anticoagulation related) and thromboembolism. Failure of liver function can occur. Thus endocrine abnormalities management and contraception are challenging. PURPOSE: to evaluate the impact on the menstrual cycles and related endocrine abnormalities in women with VLD and respective roles of liver function and portal hypertension. STUDY DESIGN: This was a single-center observational cohort study. Forty-seven premenopausal women with vascular liver disease were included for endocrine and gynecological assessments. Endocrine evaluation was performed at inclusion. Tolerance of contraception was followed up and assessed at 3 and 12 months. PARTICIPANTS, SETTING, METHODS: Forty-seven women (aged 16-50) followed in a Reference Center for Liver Vascular Disease between February 2009 and November 2016 were included and addressed for gynecological and endocrinological management. Twenty-five women had extrahepatic portal vein obstruction, 17 had Budd Chiari Syndrome and five had a porto-sinusoidal vascular disease. We explored gonadotropin at baseline and after GnRH, testosterone, sex hormone binding globulin (SHBG), androstenedione, GH axis and glucose metabolism. All women underwent pelvic ultrasonography. RESULTS: Vascular liver disease was associated with abnormal menstrual cycles in 53% of the women and clinical and/or biological hyperandrogenism and/or a polycystic ovary morphology was identified in 38%. Portal hypertension was correlated to higher testosterone levels (P = 0.04), whereas higher elevated levels SHBG in 28%, correlated with liver failure (P = 0.01). Sixteen had glucose intolerance profile or diabetes. IGF-1 levels were highly correlated with hepatic failure. Abnormal uterine bleeding occurred in 21% of women, 87% of which were due to gynecological pathologies revealed by anticoagulant treatment. Progestin contraception was well tolerated and helped to control bleeding. CONCLUSION AND IMPLICATIONS: endocrine abnormalities, prior described in association with cirrhosis, are also identified in patients with vascular liver disease, and require specific management. Glucose intolerance profile is frequent, further studies are needed to assess significant consequences on cardio-vascular system.

Metformin use is associated with a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity. REDLINC IX study.

Metformin may decrease cell senescence, including bone; hence we aimed at evaluating the association between metformin use and osteoporosis. This was a cross-sectional study carried out in 1259 Latin American adult women aged 40 or more who were not on anti-osteoporotic drugs, were on metformin and had a bone densitometry performed. Of the whole sample, 40.3% reported being on metformin (at least 1 year), 30.2% had type 2 diabetes mellitus and 22.6% had osteoporosis. Median (interquartile range) body mass index (BMI) for the whole cohort was 27.7 (4.6) kg/m2 and 30.2% had type 2 diabetes mellitus. Current use of hormone therapy, calcium, and vitamin D corresponded respectively to 10.7%, 47.7%, and 43.1% of all surveyed women. A logistic regression model was used to analyze the association of osteoporosis with various covariates incorporated into the model such as age (OR: 1.07, 95% CI: 1.05-1.09), BMI (OR: 0.92, 95% CI: 0.89-0.96) and metformin use (OR: 0.44, 95% CI: 0.32-0.59). Metformin use, regardless of the presence of type 2 diabetes or obesity, was associated with a lower risk of osteoporosis in adult women. We propose that one explanation for this observation could be the effect of the drug over cellular senescence.

The Link between Estradiol and Neuroplasticity in Transgender Women after Gender-Affirming Surgery: A Bimodal Hypothesis.

For transgender individuals, gender-affirming surgery (GAS) and cross-sex hormone therapy (CSHT) are part of the gender transition process. Scientific evidence supporting the maintenance of CSHT after GAS-related gonadectomy is accumulating. However, few data are available on the impact of CSHT on the brain structure following hypogonadism. Thus, we aimed to investigate links between estradiol and brain cortical thickness (CTh) and cognition in 18 post-gonadectomy transgender women using a longitudinal design. For this purpose, the participants underwent a voluntary period of CSHT washout of at least 30 days, followed by estradiol re-institution for 60 days. High-resolution T1-weighted brain images, hormonal measures, working and verbal memory were collected at 2 time points: on the last day of the washout (t1) and on the last day of the 2-month CSHT period (t2). Between these 2 time points, CTh increased within the left precentral gyrus and right precuneus but decreased within the right lateral occipital cortex. However, these findings did not survive corrections of multiple comparisons. Nevertheless, there was a significant negative correlation between changes in estradiol levels and changes in CTh. This effect was evident in the left superior frontal gyrus, the left middle temporal gyrus, the right precuneus, the right superior temporal gyrus, and the right pars opercularis. Although there was an improvement in verbal memory following hypogonadism correction, we did not observe a significant relationship between changes in memory scores and CTh. Altogether, these findings suggest that there is a link between estradiol and CTh.

Effects of Estradiol Therapy on Resting-State Functional Connectivity of Transgender Women After Gender-Affirming Related Gonadectomy.

An extreme incongruence between sex and gender identity leads individuals with gender dysphoria (GD) to seek cross-sex hormone therapy (CSHT), and gender-affirming surgery (GAS). Although few studies have investigated the effects of CSHT on the brain prior to GAS, no studies in the extant literature have evaluated its impact during hypogonadism in post-GAS individuals. Here, we aimed to evaluate the effects of estradiol on resting-state functional connectivity (rs-FC) of the sensorimotor cortex (SMC) and basal ganglia following surgical hypogonadism. Eighteen post-GAS (male-to-female) participants underwent functional magnetic resonance imaging (fMRI) and neuropsychiatric and hormonal assessment at two time points (t1, hormonal washout; t2, CSHT reintroduction). Based on the literature, the thalamus was selected as a seed, while the SMC and the dorsolateral striatum were targets for seed-based functional connectivity (sbFC). A second sbFC investigation consisted of a whole-brain voxel exploratory analysis again using the thalamus as a seed. A final complementary data-driven approach using multivoxel pattern analysis (MVPA) was conducted to identify a potential seed for further sbFC analyses. An increase in the rs-FC between the left thalamus and the left SCM/putamen followed CSHT. MVPA identified a cluster within the subcallosal cortex (SubCalC) representing the highest variation in peak activation between time points. Setting the SubCalC as a seed, whole-brain analysis showed a decoupling between the SubCalC and the medial frontal cortex during CSHT. These results indicate that CSHT with estradiol post-GAS, modulates rs-FC in regions engaged in cognitive, emotional, and sensorimotor processes.

Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression.

Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has been proposed for these individuals as a reversible treatment for postponing the pubertal development and attenuating psychological suffering. Recently, increased interest has been observed on the impact of this treatment on brain maturation, cognition and psychological performance. Objectives: The aim of this clinical report is to review the effects of puberty suppression on the brain white matter (WM) during adolescence. WM Fractional anisotropy, voice and cognitive functions were assessed before and during the treatment. MRI scans were acquired before, and after 22 and 28 months of hormonal suppression. Methods: We performed a longitudinal evaluation of a pubertal transgender girl undergoing hormonal treatment with GnRH analog. Three longitudinal magnetic resonance imaging (MRI) scans were performed for diffusion tensor imaging (DTI), regarding Fractional Anisotropy (FA) for regions of interest analysis. In parallel, voice samples for acoustic analysis as well as executive functioning with the Wechsler Intelligence Scale (WISC-IV) were performed. Results: During the follow-up, white matter fractional anisotropy did not increase, compared to normal male puberty effects on the brain. After 22 months of pubertal suppression, operational memory dropped 9 points and remained stable after 28 months of follow-up. The fundamental frequency of voice varied during the first year; however, it remained in the female range. Conclusion: Brain white matter fractional anisotropy remained unchanged in the GD girl during pubertal suppression with GnRHa for 28 months, which may be related to the reduced serum testosterone levels and/or to the patient's baseline low average cognitive performance.Global performance on the Weschler scale was slightly lower during pubertal suppression compared to baseline, predominantly due to a reduction in operational memory. Either a baseline of low average cognition or the hormonal status could play a role in cognitive performance during pubertal suppression. The voice pattern during the follow-up seemed to reflect testosterone levels under suppression by GnRHa treatment.

Skeletal muscle mass is associated with higher dietary protein intake and lower body fat in postmenopausal women: a cross-sectional study.

OBJECTIVE: We investigated the association between skeletal muscle mass and dietary protein intake, habitual physical activity, body composition, and metabolic variables. METHODS: One hundred three healthy postmenopausal women from southern Brazil (age 55.2 ±â€Š4.9 y, body mass index 27.2 ±â€Š4.6 kg/m) were enrolled. Bone mineral density, %body fat, %trunk fat mass, and appendicular lean mass were assessed by dual-energy x-ray absorptiometry, resting metabolic rate by indirect calorimetry, and habitual physical activity by pedometer. Skeletal muscle mass index (SMI) was expressed as appendicular lean mass standardized to body mass index. The cutoff for low lean mass was <0.512. Protein intake was measured by a validated food frequency questionnaire and categorized into tertiles: ≤0.93 g/kg body weight (BW), 0.94 to 1.29 g/kg BW, and ≥1.3 g protein/kg BW. RESULTS: The prevalence of low lean mass (SMI <0.512) was 7%. Waist circumference, %body fat, trunk fat mass, and diastolic blood pressure were higher, whereas SMI and mean daily steps were lower in women with protein intake ≤0.93 g/kg BW. SMI was positively correlated with physical activity (r = 0.205, P = 0.038) and protein intake (r = 0.334, P = 0.001), and negatively correlated with waist circumference (r = -0.505, P < 0.001) and %body fat (r = 0.808, P < 0.001). Linear regression analysis adjusted for age, time since menopause, previous smoking behavior, and energy intake showed an independent, positive contribution of protein intake (mean difference 0.007, 95% CI, 0.001-0.014, P = 0.044) and an independent, negative contribution of %body fat (mean difference -0.010, 95%CI, -0.011 to -0.008, P < 0.001) to SMI. CONCLUSIONS: In our healthy postmenopausal women, SMI was positively associated with protein intake and negatively associated with %body fat.

Associations between body composition and lifestyle factors with bone mineral density according to time since menopause in women from Southern Brazil: a cross-sectional study.

BACKGROUND: The aim of this study was to investigate whether body composition, dietary pattern and habitual physical activity are associated with BMD according to time since menopause in women from Southern Brazil with no clinical evidence of disease. METHODS: 99 participants were enrolled and anthropometry, body composition and BMD by dual energy x-ray absorptiometry, rest metabolic rate by indirect calorimetry, dietary pattern by semi quantitative food frequency questionnaire and habitual physical activity by pedometer were performed. RESULTS: Mean age was 55.2 ± 4.9 years and mean time since menopause was 6.8 ± 1.0 years. Weight, BMI, lean and fat mass and RMR were higher in women with less than 5 years since menopause with normal versus low bone mass. No differences were found in the studied variables between participants with normal or low bone mass and more than 5 years of menopause. Women with > 5 years since menopause had higher prevalence of osteoporosis, as well as lower BMD in all sites when compared to those with less time since menopause. Calories, carbohydrate, protein, fat and micronutrients intake were similar between groups. When the sample was adjusted for time since menopause, the odds ratio (OR) for low bone mass was 5.21 (95% CI 1.57-17.25, P = 0.004) for BMI <25 kg/m(2), for lean mass <37.5 Kg an OR of 4.4 (95% CI 1.64-11.80, P = 0.004, for fat mass <26.0 Kg an OR of 3.39 (95% CI 1.29-8.85, P = 0.010) and for the intake of vitamin A < 700 mcg/day an OR of 3.00 (95% CI 1.13-7.94, P = 0.012). Low meat and eggs intake or low protein intake did not influence the odds ratio for low bone mass. CONCLUSION: In this cross-sectional study with postmenopausal women with no clinical evidence of disease, time since menopause, low lean and fat mass were associated with low bone mass. Calories and macronutrients intake as well as habitual physical activity did not interfere with BMD, but participants were mostly sedentary. Further studies are needed in order to determine whether the adequate intake of specific food groups and the type of physical activity could attenuate the time since menopause impact on BMD.

Healthier dietary pattern and lower risk of metabolic syndrome in physically active postmenopausal women.

OBJECTIVES: To investigate the relationship between habitual physical activity and dietary intake, body composition, metabolic and hormonal variables, and cardiovascular risk factors in postmenopausal women with no evidence of cardiovascular disease. METHODS: In this cross-sectional study, 105 women (mean age: 55.2 ± 4.9 years) consulting for climacteric symptoms underwent anthropometric and hormonal assessment. Usual dietary intake was assessed with a food frequency questionnaire and habitual physical activity was assessed with a digital pedometer. Participants were classified as physically inactive (<6000 steps daily) or physically active (≥6000 steps daily). RESULTS: Compared to the inactive group, active women had higher protein, total fat, cholesterol, iron, calcium, and the antioxidant micronutrients zinc and selenium intake as well as differences on food groups: higher meat, egg, and whole-dairy intake and lower intake of chips. Active participants also presented lower diastolic blood pressure (p = 0.012), ultrasensitive C-reactive protein (us-CRP; p = 0.011), fasting glucose (p = 0.003), fasting insulin (p = 0.019), and homeostasis model assessment index (p = 0.017). After adjustment for age and time since menopause, the risk for metabolic syndrome increased with physical inactivity (odds ratio [OR] = 3.55, 95% confidence interval [CI], 1.08-11.66), us-CRP (OR = 6.57, 95% CI, 2.20-19.56), and percentage body fat (OR = 5.65, 95% CI, 1.19-28.89). CONCLUSION: Both physical activity and dietary choices may have contributed toward a more favorable cardiovascular profile and lower risk of metabolic syndrome in postmenopausal women.

Circulating levels and subcutaneous adipose tissue gene expression of pigment epithelium-derived factor in polycystic ovary syndrome and normal women: a case control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has been recognized as a metabolic disorder, manifested by abdominal obesity, insulin resistance, dyslipidemia and hypertension. Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor family, is a pleiotropic protein known for its antiangiogenic, antioxidant, and neuroprotective properties and has been shown to induce insulin resistance and play a role in glucose metabolism. Recent studies investigating circulating PEDF levels show elevated serum PEDF in association with insulin resistance in normal-weight women with PCOS, but not in obese PCOS patients. The aims of this study were 1) to assess PEDF gene expression in subcutaneous adipose tissue (scAT) from women with PCOS and nonhirsute, ovulatory controls, and 2) to determine the circulating levels of PEDF in these groups. METHODS: Total RNA was extracted from adipose tissue biopsy samples and reverse-transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels. RESULTS: The 22 women with PCOS and 14 non-PCOS controls included in the study had similar age, BMI, and fasting glucose, triglycerides, and HDL-cholesterol levels. Participants with PCOS exhibited higher 2 h oral glucose tolerance test levels (p = 0.006), total (p = 0.026) and LDL-cholesterol (p = 0.036), Ferriman-Gallwey score (p = 0.003) and total testosterone (p = 0.001) as compared to controls. BMI-adjusted PEDF serum levels and scAT gene expression were similar in the PCOS and control groups (p = 0.622 and p = 0.509, respectively). Circulating PEDF levels were not associated with scAT PEDF gene expression. Multiple regression analysis revealed that, in women with PCOS, insulin contributed positively and significantly to serum PEDF (p = 0.027), independently of testosterone. CONCLUSION: Serum PEDF levels and scAT gene expression were associated with metabolic risk factors, but did not differ between women with PCOS and age- and BMI-matched controls. Circulating levels and scAT gene expression of PEDF were not associated in the study subjects, suggesting additional sources for PEDF in addition to or instead of fat tissue.

Fat mass and obesity-associated gene polymorphisms do not affect metabolic response to hormone therapy in healthy postmenopausal women.

OBJECTIVE: To determine whether fat mass and obesity-associated gene polymorphisms rs9939609 T>A and rs8050136 A>C or their haplotypes influence anthropometric and metabolic variables in recently postmenopausal women receiving hormone therapy. STUDY DESIGN: In this randomized crossover study carried out in a university clinic, 86 postmenopausal women consulting for symptoms of estrogen deficiency were genotyped by real-time polymerase chain reaction for single nucleotide polymorphisms rs9939609 T>A and rs8050136 A>C of the fat mass and obesity-associated gene. Haplotypes were constructed from the combination of polymorphisms rs9939609 and rs8050136, and their frequencies were inferred using the PHASE 2.1.1 program. Participants were clinically evaluated before and after 6 months of hormone therapy to determine body mass index (current kg/m(2)) and waist circumference, blood pressure, lipid profile (total cholesterol, HDL cholesterol and triglycerides) plasma glucose (oral glucose tolerance test), and insulin. Blood samples were also drawn for ultra sensitive C reactive protein. The lipid accumulation product index was calculated as (waist [cm] - 58) × triglyceride concentration (mmol/L). Non-normally distributed parameters were log10 transformed before statistical analysis. Measurements at baseline and at follow-up were compared with ANOVA for repeated measures. Data were considered significant at P<0.05. RESULTS: In women with the homozygous polymorphic AA genotype of the single nucleotide polymorphisms rs9939609 and the wild AA genotype of the single nucleotide polymorphisms rs8050136, lipid accumulation product index and ultra sensitive C reactive protein were higher before hormone therapy in comparison with women with other genotypes from the same single nucleotide polymorphisms group. There was no worsening of any of the anthropometric or metabolic variables, and lipid accumulation product index improved slightly after hormone therapy in SNP rs9939609 (P=0.03) and haplotype AAAA. No changes were observed after hormone therapy in SNP rs8050136. CONCLUSIONS: The presence of fat mass and obesity-associated gene risk variants in healthy early postmenopausal women does not adversely affect their response to hormone therapy.

17-Hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) and treatment with oral contraceptive pills in PCOS women without metabolic comorbidities.

We studied (1) the effects of oral contraceptive pills (OCPs) on hirsutism, hormonal and metabolic variables in 49 polycystic ovary syndrome patients without metabolic comorbidities and (2) the effect of 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) on the response to OCP treatment. Mean age was 21.9 ± 6.5 years. Patients received monophasic OCP (20 µg ethinyl estradiol plus 75 µg gestodene), 21/28 days per cycle, during 6 months; 32 patients with severe hirsutism also received spironolactone 100 mg. The frequencies of HSD17B5 genotypes were: AA = 0.49 (55.1%), AG = 0.42 (30.6%) and GG = 0.09 (14.3%). After 6 months, body mass index and waist circumference remained unchanged regardless of the presence of allele G. A slight reduction (p < 0.05) was noted in systolic blood pressure (p < 0.05) and luteinizing hormone levels, whereas a slight increase (p < 0.05) was noted in lipids. Total testosterone and hirsutism score declined, while sex hormone binding globulin increased after OCP treatment (p < 0.05). None of these changes were associated with genotype. Insulin and homeostasis model assessment remained unchanged after treatment and did not vary according to the presence of allele G. OCP seems to ameliorate androgenic symptoms without compromising metabolic parameters. The -71A/G SNP of HSD17B5 gene did not contribute to the improvements observed.

CYP19 gene expression in subcutaneous adipose tissue is associated with blood pressure in women with polycystic ovary syndrome.

In polycystic ovary syndrome (PCOS), hypertension has been linked to androgen excess and insulin resistance. Aromatase, an enzyme encoded by the CYP19 gene, affects androgen metabolism and estrogen synthesis, influencing the androgen to estrogen balance. We characterized CYP19 gene expression in subcutaneous adipose tissue of women with PCOS and normal controls and evaluated the association between subcutaneous fat CYP19 mRNA, circulating hormone levels, and blood pressure. This case-control study was carried out with 31 PCOS patients and 27 BMI-matched normotensive non-hirsute women with regular cycles. Participants underwent anthropometric measurements, collection of blood samples, and adipose tissue biopsy (28 PCOS and 19 controls). Hypertension was defined as systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg. PCOS patients were divided into normotensive and hypertensive. Main outcome measures were serum estrogen and androgen levels, estrogen-to-androgen ratio, and CYP19 gene expression in subcutaneous fat. Subcutaneous CYP19 mRNA was higher in hypertensive PCOS than in control and normotensive PCOS women (p = 0.014). Estrogen-to-androgen ratio was lower in hypertensive PCOS than controls (p < 0.003). Estrogen-to-androgen ratio ≤ 0.06 (median for the three groups) was observed in 91% of hypertensive PCOS women, vs. 37% and 61% in the control and normotensive PCOS groups (p = 0.011). CYP19 gene expression in subcutaneous fat of PCOS patient correlated positively with systolic (p = 0.006) and diastolic blood pressure (p = 0.009). Androgen excess and hyperinsulinemia may play a role in the molecular mechanisms that activate aromatase mRNA transcription in abdominal fat tissue.

Expression of 17beta-hydroxysteroid dehydrogenase type 2 in pelvic endometriosis.

Lack of expression or a deficiency of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2), a key enzyme in estradiol inactivation, could be involved in the pathophysiology of endometriosis. The aim of the present study was to evaluate expression of the gene (17beta-Hsd2) encoding 17beta-HSD2 in eutopic and ectopic endometrial tissues of women with endometriosis. Thirty-four infertile women were divided into a control group, without any clinical or laparoscopic evidence of endometriosis (n = 19), and a group with pelvic endometriosis (n = 15). Diagnosis was confirmed by histological examination of the endometriotic lesions. 17beta-Hsd2 mRNA expression was detected by reverse transcription-polymerase chain reaction in the control group (54% of the samples), in the eutopic endometrium of patients with endometriosis (83% of the specimens analyzed) and in all endometriotic lesions. The semi-quantitative analysis of 17beta-Hsd2 mRNA showed a significantly higher gene expression in the endometriotic implants compared with the intrauterine endometrium of the control group (p < 0.05). 17beta-HSD2 protein was localized to the glandular epithelium of both eutopic endometrium and endometriotic implants. The present results refute the hypothesis of lower or absent 17beta-HSD2 expression in pelvic endometriosis; therefore further studies are needed to assess other potential mechanisms leading to increased estrogenic activity within endometriotic implants.

Expression of prolactin-releasing peptide and its receptor in the human decidua.

Human decidua and decidualized endometrial cells produce prolactin (PRL). Several growth factors and cytokines have been shown to regulate decidual PRL release, but a specific PRL-releasing substance remains to be characterized. Prolactin-releasing peptide (PrRP) is a peptide isolated from the brain and distinguished by its potent and specific stimulation of PRL release by cultured pituitary cells. Here, we demonstrate that human decidua expresses immunoreactive PrRP as well as the mRNAs encoding PrRP and its receptor. First trimester deciduas were obtained from women undergoing elective termination of pregnancy. Tissue specimens were stained by immunohistochemistry using a rabbit anti-human PrRP-31 antibody, and PrRP was localized in both epithelial cells of the decidual glands and in stromal cells, with diffuse distribution and no special relation with the neighbourhood of blood vessels. In primary cultures of decidual stromal cells, PrRP and PrRP receptor gene expression were detected using RT-PCR, and the identity of the PCR products was further confirmed by restriction enzyme digestion. The effect of PrRP on decidual PRL release was also evaluated, and there was a significant increase in PRL production (135 +/- 4% of control levels, P < 0.05) after incubation of decidual stromal cells with synthetic PrRP. The expression of PrRP and PrRP receptor in human decidual cells and the ability of PrRP to induce PRL secretion by cultured decidual cells suggests that this peptide may be a novel local modulator of decidual PRL release.