Serum Reproductive Hormone Concentrations Research Articles

Long-day photoperiods affect expression of OPN5 and the TSH-DIO2/DIO3 pathway in Magang goose ganders

This study sought to understand the regulation mechanism of OPN5 through the TSH-DIO2/DIO3 pathway mediated photoperiod on the breeding activity of short-day breeding birds. In this study, the reproductive activity of Magang goose was regulated by artificial light, and the reproductive activity of the ganders were determined according to the daily laying rate of female geese. The testicular development and the serum reproductive hormone concentrations of ganders were measured during the reproductive period (d 0), the reproductive degeneration period (d 13 and 27) and the resting period (d 45). The mRNA and protein expression patterns of OPN5, the HPG axis reproductive genes, and TSH-DIO2/DIO3 pathway related genes were examined. Results showed that the laying rate of geese and the gonadal indices (GSI) decreased gradually after the photoperiod increased. Histological observation found that the spermatogenic function of the testis was normal on d 0 and 13, while degeneration occurred by d 27 and 45. Serum testosterone, FSH, and LH concentration showed a slight increase on d 13, followed by a sharp decrease on d 27 and 45 (P < 0.01), while PRL concentrations were low on d 0 and 13, and increased rapidly on d 27 and 45 (P < 0.01).The expression pattern of GnRH, FSH, LH, and THRβ mRNA were similar, with high levels on d 0 and 13 and a decreasing trend on d 27 and 45 (P < 0.05 or P < 0.01); and GnRHR mRNA levels were higher on d 13 (P < 0.05), but then had decreased by d 27 and 45 (P < 0.01). The expression pattern of GnIH and GnIHR was similar, which was opposite to that of GnRHR. VIP, PRL, and PRLR increased gradually and peaked on d 45 (P < 0.01). The expression trend of TRH, TSHβ, and DIO2 was similar to that of GnRHR, and the expression abundance increased on d 13, and then decreased on d 27 and 45. GnRH protein expression was significantly higher than during the other 3 periods (P < 0.01) while the GnIH protein levels were extremely low on d 0, had gradually increased by d 13, and significantly increased by d 27 and 45 (P < 0.01). The protein expression trends of THR and DIO2 were similar to that of GNIH. DIO3 protein expression was low on d 0 and 13, and increased by d 27 and 45. These results suggest that when the photoperiod increased, the hypothalamus OPN5 gene and protein were upregulated and the pituitary TSHβ, TSHR, and hypothalamus THRβ, TRH, and DIO2 were downregulated, and thus the reproductive activity of geese was inhibited.

Associations Between Serum Reproductive Hormone Concentrations and Hormonal Receptor Status Among Postmenopausal Chinese Women With Breast Cancer: An Observational Study.

Background and ObjectivesReproductive hormones and receptors play crucial roles in breast cancer development and progression. The association between preoperative serum reproductive hormone levels and receptor status in postmenopausal women with breast cancer remains unclear. Therefore, this study investigated the relationship between serum reproductive hormone concentrations and patient characteristics and hormone receptor status among postmenopausal Chinese women with breast cancer.Materials and MethodsThe medical records of 352 postmenopausal breast cancer patients who underwent an operation between October 2007 and October 2010 at the Department of Breast Tumor Surgery of Zhejiang Cancer Hospital were retrospectively evaluated. Serum levels of reproductive hormones were measured before surgery by liquid-chromatography tandem mass spectrometry. Hormone receptor levels were measured by an immunohistochemical assay using a mouse monoclonal antibody. The associations between serum hormone concentrations and hormone receptors were investigated by analysis of covariance.ResultsIn this patient cohort, the serum level of luteinizing hormone (LH) declined with PMP duration. The median LH concentration was significantly higher in patients within 5 years of PMP than that in patients with PMP duration exceeding 5 years (23 vs. 18.32 mIU/ml, P <.0001). Significantly more patients with strong estrogen receptor (ER) or progesterone receptor (PR) expression had postmenopausal durations of less than 5 years compared to those with postmenopausal durations greater than 5 years (103 vs. 61 cases, P = .019; 93 vs. 46 cases, P = .0005). While most patients either lacked (97.1%) or co-expressed (84.3%) ER and PR, some patients expressed either ER or PR alone. ER and PR expression were negatively associated with receptor-tyrosine kinase erbB-2 (HER2) expression in postmenopausal patients with breast cancer. Meanwhile, increased ER and PR expression were associated with decreased serum levels of LH or follicle-stimulating hormone (FSH).ConclusionDecreased serum LH and FSH levels were associated with increased ER and PR expressions and decreased HER2 expression in postmenopausal patients with breast cancer.

Dynamic Changes of Reproductive Hormones in Male Minipuberty: Temporal Dissociation of Leydig and Sertoli Cell Activity.

The male hypothalamic-pituitary-gonadal (HPG) axis is transiently active during the first months of life with surging serum concentrations of reproductive hormones. This period, termed minipuberty, appears to be essential for priming testicular function. Despite the central role for male reproductive function, longitudinal data on HPG axis activation in infancy is sparse. To explore the dynamics of HPG hormone activity in healthy male infants, to assess the association of HPG axis activity and testicular volume, and to establish reference curves for serum levels of reproductive hormones. Prospective, longitudinal birth cohort (the COPENHAGEN Minipuberty Study, 2016-2018, 1-year follow-up). Population-based. Healthy, male, term, singleton newborns were followed from birth on with repeated clinical examinations including blood sampling during a 1-year follow-up. A total of 128 boys contributed to this study, while 119 participated in the postnatal follow-up. Serum reproductive hormone concentrations and testicular volume. Reproductive hormone concentrations showed marked dynamics during the first 6 months of age. Gonadotropins, total testosterone, and insulin-like factor 3 peaked at around 1 month of age. Inhibin B, anti-Müllerian hormone, and testicular volume peaked at around 4 to 5 months. Correlations largely recapitulated typical HPG axis pathways but also differed significantly from adult men. We demonstrate a temporal dissociation of Leydig and Sertoli cell activity during male minipuberty and provide reference curves for reproductive hormones.

Association between intake of soft drinks and testicular function in young men

Is intake of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) associated with testicular function in young men? Among young men unaware of their semen quality and reproductive hormone levels, intake of SSBs was associated with lower sperm concentration, lower total sperm count, and a lower ratio of serum inhibin-B/FSH. SSBs may adversely impact testicular function, but results are not consistent across studies. Moreover, the associations of ASB, energy-drinks or fruit juices with testicular function are unclear. Young healthy men and unselected for fertility status men enrolled in a cross-sectional study between 2008 and 2017. A total of 2935 young (median age: 19 years) men enrolled in the study. Intake of SSBs, ASBs, fruit juices, and energy-drinks was assessed with a validated food frequency questionnaire. Testicular function was assessed through conventional semen quality parameters (semen volume, sperm concentration, total count, motility and morphology), testicular volume assessed with ultrasound, and serum reproductive hormone concentrations (total testosterone, free testosterone, E2, inhibin-B, LH, FSH, sex hormone-binding globulin) were measured. In multivariable-adjusted analyses, men in the highest category of SSB intake (median: 1.1 servings (∼220 ml)/day) had a 13.2 million/ml lower median sperm concentration (95% CI: -21.0, -5.5) than non-consumers. A similar pattern was observed with total sperm count (-28 million (95% CI: -48, -9)), serum inhibin-B (-12 pg/ml (95% CI: -21, -4)), and inhibin-B/FSH ratio (-9 (95% CI: -18, 0)). The adjusted median difference in sperm concentration and inhibin-B associated with increasing SSB intake by 1 serving (∼200ml)/day at the expense of water was -3.4 million sperm/ml (95% CI: -5.8, -1.0) and -7 pg/ml (95% CI: -11, -3), respectively. Inferring causality is limited owing to the cross-sectional design. We adjusted for a number of potential confounders but cannot exclude that unmeasured lifestyle and behavior associated with soft drink intake is associated with testicular function in these young men. In the largest study to date, intake of SSBs was associated with lower sperm concentration, total sperm count, and serum inhibin-B/FSH ratio, consistent with a direct suppressive effect of SSB intake on testicular function among otherwise healthy men, potentially affecting fertility. However, the observed association between higher SSB intake and lower semen quality does not necessarily imply a decrease in fertility. Supported by research from the Danish Council for Strategic Research (2101-08-0058), Independent Research Fund Denmark (8020-00218B), European Union (212844), the Kirsten and Freddy Johansen's Foundation (95-103-72087), the Research Fund of the Capital Region of Denmark (A6176), and the NIH (P30DK046200). The authors report no conflict of interest. N/A.

Isomaltooligosaccharide and Bacillus regulate the duration of farrowing and weaning-estrous interval in sows during the perinatal period by changing the gut microbiota of sows.

This study investigated the effects of isomaltooligosaccharide (IMO) and Bacillus in perinatal diets on the duration of farrowing and post-weaning estrus, serum reproductive hormone concentrations, and gut microbiota and its metabolites of sows. Multiparous sows (n = 130) were fed diets without IMO (control, CON group), or diets containing only IMO (IMO group), IMO and Bacillus subtilis (IMOS group), IMO and Bacillus licheniformis (IMOL group), and IMO and B. subtilis and B. licheniformis (IMOSL group), respectively. The results indicate that the duration of farrowing and post-weaning estrus was shorter in sows in the IMOS, IMOL, and IMOSL groups, and the weaning-estrous interval was lower in sows in the IMOL greoup. In addition, the lowest fecal score was observed in the IMOL group during d 106 to 112 of gestation. Sows in most of the treatment groups had a higher concentration of serum prolactin and prostaglandin at farrowing, but a lower serum concentration of estradiol, oxytocin, and progesterone on d 18 of lactation than sows in the CON group. The treatment groups had a higher abundance of Candidatus Methanoplasma and Bacillus and a lower abundance of Escherichia-Shigella in their feces at farrowing. Furthermore, the treatment groups had higher concentrations of total short-chain fatty acids (SCFA) in feces at farrowing and a higher concentration of branched fatty acids in feces on d 18 of lactation. Furthermore, the abundance of Bacillus in feces was positively correlated with serum prostaglandin concentrations and fecal total SCFA of sows at farrowing, but was negatively correlated with the duration of farrowing. Overall, dietary IMO and Bacillus supplementation affected the concentration of serum reproductive hormones and the duration of farrowing and post-weaning estrus, and the gut microbiota is a key factor.

Assessment of Serum Reproductive Hormone Concentrations in Normal Pregnancy

Assessment of Serum Reproductive Hormone Concentrations in Normal Pregnancy

786-P: Serum Dehydroepiandrosterone Sulfate Concentration and Animal Protein Intakes Are Important Factors for Skeletal Muscle Mass in Japanese Patients with Type 2 Diabetes

The aim of this study was to examine the association between serum reproductive hormone concentrations, dietary intakes and skeletal muscle mass in patients with type 2 diabetes. This cross-sectional study investigated 54 Japanese patients with type 2 diabetes (32 males) during the period between 2014 to 2018. All patients completed measurements of serum dehydroepiandrosterone sulfate concentration (DHEA-S), skeletal muscle index (SMI) and dietary intakes at same period. Those who had adrenal tumor, thyroid cancer, and thyroid dysfunction were excluded. In the analysis, as a first-step, we conducted single regression analysis between age, DHEA-S, SMI, total energy and each macronutrient intakes. SMI was positively correlated with total energy and protein intakes. Interestingly, while protein intakes derived from animal foods were positively correlated with SMI, those from plant foods showed negative correlation. On the other hand, DHEA-S was positively correlated with SMI. Then, multiple regression analysis (MRS) was performed to examine the contributors to SMI (Table). MRS revealed the association of SMI with DHEA-S and protein intakes. Our data suggest that DHEA-S and protein intakes are the factors contribute to SMI in Japanese patients with type 2 diabetes. Disclosure S. Moyama: None. H. Kuwata: Research Support; Self; Eli Lilly and Company. Y. Hamamoto: Speaker's Bureau; Self; Novo Nordisk A/S. D. Yabe: Advisory Panel; Self; Abbott. Research Support; Self; Astellas Pharma Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Seino: Research Support; Self; Arkray, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation.

Ethanolic Seed Extract of Garcinia kola Reduces Epididymal Sperm Count and Some Serum Reproductive Hormone Concentrations in Adult Male Albino Wistar Rats

Ethanolic Seed Extract of Garcinia kola Reduces Epididymal Sperm Count and Some Serum Reproductive Hormone Concentrations in Adult Male Albino Wistar Rats

The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age.

Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated “free” serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20–22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at −80°C, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry. TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = −0.22) and sums of DEHP and DiNP metabolites (r = −0.24) and the sum of the metabolites of the high molecular weight phthalates (r = −0.21) were negatively correlated with TV (all p < 0.05). After adjustment for BMI adult serum total testosterone was positively associated with exposure to the following antenatal serum phthalate metabolites: mono-(2-ethylhexyl) phthalate (r = 0.26), MiNP (r = 0.18), the sum of metabolites for DEHP (r = 0.21) and DiNP (r = 0.18), and the sum of high molecular phthalates (r = 0.20) (p = 0.0005 to p = 0.02). Given sample size, storage duration and confounding through postnatal exposures, further studies are required.

Residential distance to major roadways and semen quality, sperm DNA integrity, chromosomal disomy, and serum reproductive hormones among men attending a fertility clinic.

We examined associations of residential distance to major roadways, as a proxy for traffic-related air pollution exposures, with sperm characteristics and male reproductive hormones. The cohort included 797 men recruited from Massachusetts General Hospital Fertility Center between 2000 and 2015 to participate in fertility research studies. Men reported their residential addresses at enrollment and provided 1-6 semen samples and a blood sample during follow-up. We estimated the Euclidean distance to major roadways (e.g. interstates and highways: limited access highways, multi-lane highways (not limited access), other numbered routes, and major roads) using information from the Massachusetts Department of Geographic Information Systems. Semen parameters (1238 semen samples), sperm DNA integrity (389 semen samples), chromosomal disomy (101 semen samples), and serum reproductive hormones (405 serum samples) were assessed following standard procedures. Men in this cohort were primarily Caucasian (86%), not current smokers (92%), with a college or higher education (88%), and had an average age of 36 years and BMI of 27.7 kg/m2. The median (interquartile range) residential distance to a major roadway was 111 (37, 248) meters. Residential proximity to major roadways was not associated with semen parameters, sperm DNA integrity, chromosomal disomy, or serum reproductive hormone concentrations. The adjusted percent change (95% CI) in semen quality parameters associated with a 500 m increase in residential distance to a major roadway was -1.0% (-6.3, 4.5) for semen volume, 4.3% (-5.8, 15.7) for sperm concentration, 3.1% (-7.2, 14.5) for sperm count, 1.1% (-1.2, 3.4) for % total motile sperm, and 0.1% (-0.3, 0.5) for % morphologically normal sperm. Results were consistent when we modeled the semen parameters dichotomized according to WHO 2010 reference values. Residential distance to major roadways, as a proxy for traffic-related air pollution exposure, was not related to sperm characteristics or serum reproductive hormones among men attending a fertility clinic in Massachusetts.

Postnatal Changes in Testicular Position Are Associated With IGF-I and Function of Sertoli and Leydig Cells.

Despite clinical guidelines calling for repetitive examination of testicular position during childhood, little is known of normal changes in testicular position during childhood, let alone factors that control it. To assess changes in and factors associated with testicular position during childhood. Testicular position (the distance from the pubic bone to the upper pole of the testes) at birth, 3 months, 18 months, 36 months, and 7 years and reproductive hormones at 3 months were measured. Prenatally recruited, prospective longitudinal birth cohort. A total of 2545 boys were recruited prenatally in a Danish-Finnish birth cohort and had a testicular position examination available. A subset of 680 Danish and 362 Finnish boys had serum reproductive hormone concentrations and insulin-like growth factor I (IGF-I) determined at 3 months. Testicular distance to pubic bone (TDP), serum reproductive hormone, and IGF-I concentrations. TDP increased from birth to 3 months and decreased thereafter. Length, gestational age, weight for gestational age, and penile length were positively associated with larger TDP and thus lower testicular position in a linear mixed-effect model. Furthermore, IGF-I concentration, inhibin B/follicle-stimulating hormone ratio, and testosterone/luteinizing hormone ratio were all independently and positively associated with longer TDP. We provide longitudinal data on postnatal changes in TDP. TDP is dynamic and associated with Leydig and Sertoli cell function as well as with IGF-I levels during the first months of life at mini-puberty of infancy. TDP may thus be a useful biomarker of postnatal testicular function.

The influence of maternal phthalate exposure upon adult male reproductive function

Phthalates are ubiquitous environmental chemicals suspected to possess anti-androgenic hormone disrupting properties. Some evidence exists of a possible negative impact of exposure on male reproductive development. The aim of this study was to determine the associations between antenatal phthalate exposure and testicular volume, semen parameters and serum reproductive hormone concentrations in adulthood.

Endemic fluorosis in Henan province, China: ERα gene polymorphisms and reproductive hormones among women.

The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence. A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride. In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05). Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.

Associations between oxidative stress biomarkers in different body fluids and reproductive parameters in male partners of subfertile couples

ObjectiveTo evaluate the relationships between oxidative stress (OS) biomarkers and total antioxidant capacity (TAC) in blood serum and seminal plasma, and their associations with semen quality and serum reproductive hormone concentrations in potential subfertile men. Material and methodA cross-sectional study was conducted on men (n=122) attending an infertility clinic in the Murcia Region (Southern Spain) between 2012 and 2013. Concentrations of malondialdehyde (MDA), nitric oxide (NO) and TAC were measured in blood and semen. Follicle-stimulating hormone, luteinising hormone, testosterone, prolactin and oestradiol concentrations were measured in serum. Semen analyses were performed according to World Health Organization criteria. Correlation analysis and multiple linear regression models were performed, controlling for important covariates. ResultsThere was a significant inverse association between serum MDA concentrations and all sperm parameters, except for seminal volume. Serum TAC concentrations were positively related to sperm count and motility. A positive association was observed between seminal plasma NO levels and the percentage of morphologically normal sperm. With regard to reproductive hormones, serum MDA concentrations were positively related to FSH and LH levels, and TAC inversely associated with FSH levels. ConclusionsOur results suggest that oxidative stress may be associated with semen parameters and reproductive hormone levels in male partners of couples seeking infertility treatment. However, further studies are needed to confirm and extend these findings, in particular, with regard to serum reproductive hormones.

Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis.

GnRH sterilization vaccines have been developed for various practical and clinical reasons. However, conjugation of GnRH peptide to carrier protein has many drawbacks, hampering the further commercialization of GnRH vaccines. In this study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK), emulsified in Specol adjuvant was investigated for its immunocastration efficacy in young male rats. Prepubertal male rats were randomly allocated into three groups (n = 12): control (no treatment), surgically castrated or immunized against 100 μg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (18 weeks of age). Compared to intact controls, active immunization against TDK reduced (P < 0.05) serum concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor, FSH receptor, inhibin α, βA and βB subunit in the testes were decreased in immunocastrated rats compared to intact controls (P < 0.05). These results demonstrate for the first time that GnRH-tandem-dimer peptide emulsified in Specol is a promising veterinary sterilization medicine.

Aqueous seed extract of Cola nitida rubra reduces serum reproductive hormone concentrations and sperm count in adult male albino Wistar rats.

Background:Following the high rate of consumption of Cola nitida (cola nut) among the male population in Nigeria, this study seeks to determine the effects of consumption of Cola nitida on serum reproductive hormones and sperm count, which are major determinants of male fertility.Materials and Methods:Thirty-two male albino wistar rats weighing 180-220 g were used for this study and were divided into 4 groups of eight animals each. Group 1 served as control, group 2 received 2 mg/kg Cola nitida extract (Test 1), group 3 received 6 mg/kg Cola nitida extract (Test 2) and group 4 received 10 mg/kg Cola nitida extract (Test 3). After 6 weeks of treatment, reproductive hormonal assay was carried out using the rat serum. Epididymal spermatozoa were collected and sperm count determined.Results:Serum concentrations of luteinizing hormone (LH) and testosterone were significantly (P < 0.05) reduced in test 2 and 3, compared with control. Sperm count was significantly lower in test group 1 (P < 0.05), 2 (P < 0.001) and 3 (P < 0.001) compared with control, with test 3 significantly (P < 0.05) lower compared with test 1. There was no significant difference in testicular and epididymis weight in the different experimental groups studied.Conclusion:Aqueous seed extract of Cola nitida rubra resulted in reduced serum reproductive hormone concentrations and sperm count in male wistar rats, and may therefore be detrimental to reproductive health, hence the need for regulation of its consumption.

On Using Summary Statistics From an External Calibration Sample to Correct for Covariate Measurement Error

Covariate measurement error is common in epidemiologic studies. Current methods for correcting measurement error with information from external calibration samples are insufficient to provide valid adjusted inferences. We consider the problem of estimating the regression of an outcome Y on covariates X and Z, where Y and Z are observed, X is unobserved, but a variable W that measures X with error is observed. Information about measurement error is provided in an external calibration sample where data on X and W (but not Y and Z) are recorded. We describe a method that uses summary statistics from the calibration sample to create multiple imputations of the missing values of X in the regression sample, so that the regression coefficients of Y on X and Z and associated standard errors can be estimated using simple multiple imputation combining rules, yielding valid statistical inferences under the assumption of a multivariate normal distribution. The proposed method is shown by simulation to provide better inferences than existing methods, namely the naive method, classical calibration, and regression calibration, particularly for correction for bias and achieving nominal confidence levels. We also illustrate our method with an example using linear regression to examine the relation between serum reproductive hormone concentrations and bone mineral density loss in midlife women in the Michigan Bone Health and Metabolism Study. Existing methods fail to adjust appropriately for bias due to measurement error in the regression setting, particularly when measurement error is substantial. The proposed method corrects this deficiency.

Long-Term Effects of Valproic Acid on Reproductive Endocrine Functions in Turkish Women with Epilepsy

The long-term effects of valproic acid (VPA) on reproductive endocrine functions in women with epilepsy (WWE) were studied. Serum reproductive hormone concentrations, clinical findings and ovarian morphology were analyzed in 71 WWE who had been receiving antiepileptic drugs (AED) for a minimum of 2 years. Of the 71 WWE, polycystic ovarian syndrome (PCOS) (p = 0.011) and menstrual irregularities (p = 0.009) were found to be more prevalent in women receiving VPA treatment when compared to women on non-VPA treatment. There was no statistically significant dose or duration-related rise of risk for patients who developed PCOS and menstrual irregularities and those who were not on long-term VPA therapy. The lack of a duration-related reproductive dysfunction in this patient population may support the hypothesis of early occurring VPA-associated metabolic and endocrine changes.

Sodium Valproate, Hyperandrogenism and Altered Ovarian Function in Indian Women with Epilepsy: A Prospective Study

To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy. Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy. Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p=0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r=0.66, p<0.0001), hirsutism (r=0.53, p=0.006) and PCO (r=0.51, p=0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards. Limitations include small sample size and a high dropout rate on follow-up. Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS.

Long-term reproductive endocrine health in young women with epilepsy during puberty.

To evaluate the outcome of epilepsy and later reproductive endocrine health in girls who had epilepsy during puberty, using a population-based controlled study. Sixty-nine patients (88%) and 51 control subjects (94%) of previously identified cohorts of 78 girls with epilepsy and 54 healthy control girls participated in this study (initial age 8 to 18.5 years, at follow-up 12.5 to 25.8 years). Thirty-five of the patients were initially taking valproate (VPA), 17 carbamazepine, and 17 oxcarbazepine as monotherapy. Most of the patients (61%) were off medication. All the subjects were examined clinically, the medical and menstrual histories were obtained, ovarian ultrasonography was examined, and serum reproductive hormone concentrations were analyzed. There were no significant differences in laboratory or clinical findings between the patients off medication and the control subjects. Postpubertal patients on medication had higher serum testosterone (1.9 nmol/L, SD 0.7 nmol/L) and androstenedione (18.8 nmol/L, SD 15.2 nmol/L) levels than patients off medication (1.4 nmol/L, SD 0.5 nmol/L, and 9.5 nmol/L, SD 2.6 nmol/L) or control subjects (1.4 nmol/L, SD 0.5 nmol/L, and 10.2 nmol/L, SD 3.2 nmol/L) (all comparisons p < 0.02). All patients still on VPA had elevated serum androstenedione levels. Polycystic ovary syndrome was more common in patients on medication (38%; in 63% on VPA, in 25% on other medication) than in patients off medication (6%) or in controls (11%) (p = 0.005). Epilepsy during pubertal maturation does not affect reproductive endocrine health in female subjects who discontinue the medication before adulthood. However, an increased prevalence of endocrine disorders is detected if the patients remain on antiepileptic drugs, especially VPA, until adulthood.