Postnatal Assessment of Minipuberty in Indian Preterm and Full-term Male Infants.

OBJECTIVES: To study the differences in the timing and magnitude of postnatal urinary gonadotropins and testosterone secretion during minipuberty in Indian preterm (PT) and full-term (FT) male infants. METHODS: This prospective observational study included 30 PT and 60 FT male infants. Urinary luteinizing hormone (LH), follicular stimulating hormone (FSH), and testosterone, and stretched penile length (SPL) and testicular volume (TV) were measured on day 7, first month, second month, fourth month and at six months of age. RESULTS: The highest elevation of mean (SD) urinary LH was observed in PT infants in comparison to FT infants [12.6 (1.4) vs 4.9 (0.6) µIU/mg, respectively; P < 0.001] in the first month. FSH levels were lower in PT than FT infants on day 7 (P < 0.001). Testosterone was significantly elevated in PT than FT infants [70.8 (5.6) vs 44.6 (3.2) ng/mg; P < 0.001] with a greater mean percentage increase in SPL (P < 0.001) and TV (P < 0.001) by the first month. CONCLUSIONS: Indian PT male infants showed a greater increase in urinary LH and testosterone, with a faster increase in SPL and TV.

Quantifying the variability in the assessment of reproductive hormone levels.

OBJECTIVE: To quantify how representative a single measure of reproductive hormone level is of the daily hormonal profile using data from detailed hormonal sampling in the saline placebo-treated arm conducted over several hours. DESIGN: Retrospective analysis of data from previous interventional research studies evaluating reproductive hormones. SETTING: Clinical Research Facility at a tertiary reproductive endocrinology centre at Imperial College Hospital NHS Foundation Trust. PATIENTS: Overall, 266 individuals, including healthy men and women (n = 142) and those with reproductive disorders and states (n = 124 [11 with functional hypothalamic amenorrhoea, 6 with polycystic ovary syndrome, 62 women and 32 men with hypoactive sexual desire disorder, and 13 postmenopausal women]), were included in the analysis. INTERVENTIONS: Data from 266 individuals who had undergone detailed hormonal sampling in the saline placebo-treated arms of previous research studies was used to quantify the variability in reproductive hormones because of pulsatile secretion, diurnal variation, and feeding using coefficient of variation (CV) and entropy. MAIN OUTCOME MEASURES: The ability of a single measure of reproductive hormone level to quantify the variability in reproductive hormone levels because of pulsatile secretion, diurnal variation, and nutrient intake. RESULTS: The initial morning value of reproductive hormone levels was typically higher than the mean value throughout the day (percentage decrease from initial morning measure to daily mean: luteinizing hormone level 18.4%, follicle-stimulating hormone level 9.7%, testosterone level 9.2%, and estradiol level 2.1%). Luteinizing hormone level was the most variable (CV 28%), followed by sex-steroid hormone levels (testosterone level 12% and estradiol level 13%), whereas follicle-stimulating hormone level was the least variable reproductive hormone (CV 8%). In healthy men, testosterone levels fell between 9:00 am and 5:00 pm by 14.9% (95% confidence interval 4.2, 25.5%), although morning levels correlated with (and could be predicted from) late afternoon levels in the same individual (r2 = 0.53, P<.0001). Testosterone levels were reduced more after a mixed meal (by 34.3%) than during ad libitum feeding (9.5%), after an oral glucose load (6.0%), or an intravenous glucose load (7.4%). CONCLUSION: Quantification of the variability of a single measure of reproductive hormone levels informs the reliability of reproductive hormone assessment.

Progesterone-primed cycles result in slower embryos without compromising implantation potential and with the advantages of oral administration and potential cost reduction.

OBJECTIVE: To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles. DESIGN: Cohort study. SETTING: Private university-affiliated in vitro fertilization center. PATIENT(S): This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups. INTERVENTION(S): The kinetic recorded markers were time to pronuclear appearance and fading, time to 2-8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups. MAIN OUTCOME MEASURE(S): Embryo morphokinetics and clinical outcomes. RESULTS: Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively. CONCLUSIONS: Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.

Assessment of the In Vivo Reprotoxicity of Isotretinoin in Sprague-Dawley Male Rat.

BACKGROUND: Isotretinoin (ISO) belongs to a family of drugs called retinoids. It is the most effective drug prescribed by dermatologists for the treatment of the inflammatory disease, acne vulgaris. A significant barrier to the use of ISO has worries regarding its adverse effect profile. Despite the well-recognized reproductive toxicity and teratogenicity in females, there is no warning related to the use by male patients in the medication prospectus. Current data on the effects on human male fertility is contradictory and inconclusive. OBJECTIVES: This study was undertaken to investigate the potential effects of ISO oral doses in the Sprague-Dawley male rat germ cells using the sperm morphology assay. Also, the serum levels of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured. METHODS: The rat groups were given varying ISO doses via gastric gavage for seven consecutive days. The epididymis sperm specimens were microscopically examined for the following reproductive toxicity parameters: sperm concentration, examined viability, motility, and morphology. The serum FSH, LH, and testosterone levels were measured by using the corresponding enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed statistically by one-way analysis of variance (ANOVA) followed by the Tukey test at P ≤ 0.05 significance level. RESULTS: The results indicated that the drug did not significantly increase the sex hormone levels but notably affected both the sperm quantity and quality. CONCLUSION: These observations suggest that ISO was reprotoxic, and future therapies should be further reassessed.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes.

OBJECTIVES: Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR). METHODS: This cross-sectional study included 399 children and youth aged 6-23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging. RESULTS: Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects. CONCLUSIONS: The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control.

A Quadruplex Ultrasensitive Immunoassay for Simultaneous Assessment of Human Reproductive Hormone Proteins in Multiple Biofluid Samples.

Reproductive hormones play vital roles in reproductive health and can be used to assess a woman's ovarian function and diagnose diseases associated with reproductive endocrine disorders. As these hormones are important biomarkers for reproductive health monitoring and diagnosis, a rapid, high-throughput, and low-invasive detection and simultaneous assessment of the levels of multiple reproductive hormones has important clinical applications. In this work, a quadruplex ultrasensitive immunoassay was developed for simultaneous assessment of 4 human reproductive hormone proteins (follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and anti-Müllerian hormone (AMH)) in a variety of human biofluid samples. This assay takes advantage of single-molecule imaging of microwell arrays and capture antibody beads as a reaction interface to construct multiplex bead array immunoassays. The analyte-bound beads can easily be parsed to individual wells and detected via fluorophores, emitting distinct wavelengths associated to the beads. As a result, this proposed quadruplex immunoassay exhibits four good 4-parameter logistic calibration curves ranging from 2.7 to 2000, 1.6 to 1200, 1.8 to 1300, and 0.3 to 220 pg/mL with limits of detection of 0.32, 0.28, 0.14, and 0.02 pg/mL for FSH, LH, PRL, and AMH, respectively. Furthermore, the developed quadruplex immunoassay was used to test clinical venous serum samples where it showed remarkable consistency with clinical test results in methodological comparison and the diagnosis of polycystic ovary syndrome. In addition, we successfully applied the ultrasensitive capability of this assay to the simultaneous testing and evaluation of four proteins in fingertip blood as well as urine samples, in which the urinary AMH level (1.42-156 pg/mL) was measured and assessed quantitatively for the first time.

Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial.

INTRODUCTION: This phase 3, randomized, open-label, active-controlled, multicenter study investigated the efficacy of triptorelin pamoate prolonged-release (PR) 3-month in Chinese patients with endometriosis by demonstrating the noninferiority of the 3-month formulation to the standard of care, triptorelin acetate PR 1-month. METHODS: The trial was conducted in 24 clinical centers in China, and included 300 Chinese women (18-45 years) with endometriosis and regular menstrual cycles who required treatment with a gonadotropin-releasing hormone agonist for 6 months. One group of patients (n = 150) was treated with triptorelin pamoate PR 3-month (15 mg per injection, once every 12 weeks), and the other (n = 150) with triptorelin acetate PR 1-month (3.75 mg per injection, once every 4 weeks). The primary outcome measure was the proportion of patients with estradiol (E2) concentrations suppressed to castration levels (≤ 184 pmol/L, or 50 pg/mL) after 12 weeks of treatment. RESULTS: Triptorelin pamoate PR 3-month was noninferior to triptorelin acetate PR 1-month for the treatment of endometriosis: over 98% of patients in both groups were chemically castrated at week 12. Both formulations were also equally efficacious in reducing endometriosis-associated pelvic pain, and reducing serum concentrations of E2, luteinizing hormone, and follicle-stimulating hormone over time. No new safety concerns were identified. CONCLUSION: Triptorelin pamoate PR 3-month is a valid alternative to triptorelin acetate PR 1-month for the treatment of Chinese women with endometriosis, with fewer injections and a potentially lower burden of care. TRIAL REGISTRATION: NCT03232281.

Vitamin D status and parathyroid hormone assessment in girls with central precocious puberty.

PURPOSE: The objective of this study was to analyze vitamin D status and PTH concentrations in 6- to 8-year-old girls with central precocious puberty. METHODS: A cross-sectional clinical and blood testing study (calcium, phosphorus, 25(OH)D and PTH) was carried out in 78 girls with central precocious puberty (CPP group), aged 6.1-7.9 years. A control group was recruited (137 prepubertal girls, aged 6.1-8.2 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. RESULTS: There were no significant differences in vitamin D status between both groups. There were no significant differences in 25(OH)D concentrations between CPP (25.4 ± 8.6 ng/mL) and control groups (28.2 ± 7.4 ng/mL). In contrast, PHT concentrations in CPP group (44.8 ± 16.3 pg/mL) were higher (p < 0.05) with respect to control group (31.0 ± 11.9 ng/mL). In CPP group, there was a positive correlation (p < 0.05) between PTH concentrations and growth rate, bone age, and basal estradiol, basal FSH, basal LH and LH peak concentrations. CONCLUSION: Vitamin D status in 6- to 8-year-old girls with CPP is similar to that in prepubertal girls. PTH concentrations were significantly higher in girls with CPP, and this could be considered as a physiological characteristic of puberty and, in this case, of pubertal precocity.

Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome.

OBJECTIVE: To study whether artificial intelligence (AI) technology can be used to discern quantitative differences in endometrial immune cells between cycle phases and between samples from women with polycystic ovary syndrome (PCOS) and non-PCOS controls. Only a few studies have analyzed endometrial histology using AI technology, and especially, studies of the PCOS endometrium are lacking, partly because of the technically challenging analysis and unavailability of well-phenotyped samples. Novel AI technologies can overcome this problem. DESIGN: Case-control study. SETTING: University hospital-based research laboratory. PATIENT(S): Forty-eight women with PCOS and 43 controls. Proliferative phase samples (26 control and 23 PCOS) and luteinizing hormone (LH) surge timed LH+ 7-9 (10 control and 16 PCOS) and LH+ 10-12 (7 control and 9 PCOS) secretory endometrial samples were collected during 2014-2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometrial samples were stained with antibodies for CD8+ T cells, CD56+ uterine natural killer cells, CD68+ macrophages, and proliferation marker Ki67. Scanned whole slide images were analyzed with an AI deep learning model. Cycle phase differences in leukocyte counts, proliferation rate, and endometrial thickness were measured within the study populations and between the PCOS and control samples. A subanalysis of anovulatory PCOS samples (n = 11) vs. proliferative phase controls (n = 18) was also performed. RESULT(S): Automated cell counting with a deep learning model performs well for the human endometrium. The leukocyte numbers and proliferation in the endometrium fluctuate with the menstrual cycle. Differences in leukocyte counts were not observed between the whole PCOS population and controls. However, anovulatory women with PCOS presented with a higher number of CD68+ cells in the epithelium (controls vs. PCOS, median [interquartile range], 0.92 [0.75-1.51] vs. 1.97 [1.12-2.68]) and fewer leukocytes in the stroma (CD8%, 3.72 [2.18-4.20] vs. 1.44 [0.77-3.03]; CD56%, 6.36 [4.43-7.43] vs. 2.07 [0.65-4.99]; CD68%, 4.57 [3.92-5.70] vs. 3.07 [1.73-4.59], respectively) compared with the controls. The endometrial thickness and proliferation rate were comparable between the PCOS and control groups in all cycle phases. CONCLUSION(S): Artificial intelligence technology provides a powerful tool for endometrial research because it is objective and can efficiently analyze endometrial compartments separately. Ovulatory endometrium from women with PCOS did not differ remarkably from the controls, which may indicate that gaining ovulatory cycles normalizes the PCOS endometrium and enables normalization of leukocyte environment before implantation. Deviant endometrial leukocyte populations observed in anovulatory women with PCOS could be interrelated with the altered endometrial function observed in these women.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

PURPOSE: This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. METHODS: PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. RESULTS: Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. CONCLUSION: Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Assessment of Ferula hermonis Boiss fertility effects in immature female rats supported by quantification of ferutinin via HPLC and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula hermonis is a small shrub renowned for its aphrodisiac abilities. Middle East herbalists have utilized Ferula hermonis seed and root as an aphrodisiac folk medicine to treat women's frigidity and male erectile and sexual dysfunction. AIM OF THE STUDY: Assessment of follicle-stimulating hormone-like (FSH), luteinizing hormone-like (LH), and estrogenic activities of the methanolic extract (ME) of the roots of Ferula hermonis on female reproductive function. MATERIALS AND METHODS: The methanolic extract was prepared from the root of F. hermonis and studied at dose level 6 mg/kg in immature female rats for FSH-like, LH-like, and estrogenic activities. These activities were determined by analyzing gross anatomical features, relative organ weight, and serum level of FSH, LH, progesterone and estrogen hormones, and histopathological characteristics. Quantification of the main phytoestrogenic component ferutinin carried out by HPLC. In addition, molecular docking for the binding affinity of ferutinin inside active sites of both estrogen receptor alpha (ERα) and FSH receptor (FSHR) was performed to predict the potential role of ferutinin in regulating the female reproductive process. RESULTS: Ferula hermonis (ME) showed potent FSH-like, LH-like activities and moderate estrogenic effect at the dose of 6 mg/kg. The content of ferutinin in F. hermonis was estimated to be 92 ± 1.33 mg/g of the methanolic extract. Molecular docking of ferutinin with ERα and FSHR displayed strong interaction with target proteins. CONCLUSIONS: Based on results, it can be concluded that Ferula hermonis can be considered as a suitable female fertility improving agent.

Replicability of leptin associations with testosterone, estradiol, follicle-stimulating hormone, and luteinizing hormone in healthy Ache men of Paraguay: A multiple daily assessment.

OBJECTIVE: Associations between leptin and male reproductive hormone levels have been reported in men. However, few of these investigations have focused on associations in healthy men without obesity or overweight or nonindustrial societies. METHODS: We test hypotheses that leptin is associated with testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) within healthy Ache men, an indigenous nonindustrialized South American community using archived data. RESULTS: Archived data of serum FSH, LH, leptin, and salivary testosterone and estradiol levels collected from healthy Ache men (n = 17, mean age = 37.1 ± 14.2) on two separate days revealed leptin was correlated with FSH (D1 p = .07, D2 p = .009) and PM testosterone (TsalPM, D1 p = .05, D2 p = .05). However, controlling for age, associations with FSH were not significant. Mean comparisons and linear regression of values over 2 days resulted in leptin (t = 0.08, p = .94, r2  = .58, p = .0009), LH (t = 1.16, p = .26, r2  = .11, p = .27), FSH (U = 131.5, p = .88, r2  = .63, p = .0002), AM testosterone (TsalAM, t = 4.0, p = .001, r2  = .02, p = 0.75), and TsalPM (t = 2.99, p = .01, r2  = .56, p = .01). CONCLUSION: We conclude (a) FSH, TsalPM, and leptin levels within individual men are relatively invariant over a span of days; (b) despite small sample sizes, results suggest ecological and lifestyle variation can contribute to variation in leptin associations with male reproductive hormones.

Assessment of Gonadotropin Concentrations Stimulated by Gonadotropin-Releasing Hormone Analog by Electrochemiluminescence in Girls with Precocious Puberty and Premature Thelarche.

OBJECTIVE: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic-pituitary-gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. METHODS: A total of 49 girls underwent the stimulation test with an intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. RESULTS: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). The LH peak was found at 60 min after stimulation. CONCLUSIONS: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

The power of modelling pulsatile profiles.

The quantitative description of individual observations in non-linear mixed effects models over time is complicated when the studied biomarker has a pulsatile release (e.g. insulin, growth hormone, luteinizing hormone). Unfortunately, standard non-linear mixed effects population pharmacodynamic models such as turnover and precursor response models (with or without a cosinor component) are unable to quantify these complex secretion profiles over time. In this study, the statistical power of standard statistical methodology such as 6 post-dose measurements or the area under the curve from 0 to 12 h post-dose on simulated dense concentration-time profiles of growth hormone was compared to a deconvolution-analysis-informed modelling approach in different simulated scenarios. The statistical power of the deconvolution-analysis-informed approach was determined with a Monte-Carlo Mapped Power analysis. Due to the high level of intra- and inter-individual variability in growth hormone concentrations over time, regardless of the simulated effect size, only the deconvolution-analysis informed approach reached a statistical power of more than 80% with a sample size of less than 200 subjects per cohort. Furthermore, the use of this deconvolution-analysis-informed modelling approach improved the description of the observations on an individual level and enabled the quantification of a drug effect to be used for subsequent clinical trial simulations.

Assessment of sexual hormones in foundry workers exposed to heat stress and electromagnetic fields.

The presence of hazardous agents in workplaces has raised concerns regarding their possible impacts on male reproductive system. The present study investigated the individual and combined effects of exposure to heat stress and electromagnetic fields with low-frequency characteristics on the levels of sex hormones in two foundry sections (Aluminum and Cast Iron) of an automobile parts manufacturing plant. The level of workers' exposure (n = 110) to each of the mentioned stressors, was measured through standard methods and for each person and the time-weighted average (TWA) of exposure was calculated. The participants of each sections were classified into separate exposure groups based on the 33rd and 66th percentile of the level of to heat stress and electromagnetic fields exposure. In order to determine serum sex hormones, blood samples were taken from all participants between 7-9 am and then the blood samples were analyzed by ELISA method. In total of two sections, the lowest mean testosterone levels was observed in the third exposure group of the electromagnetic fields (magnetic field>1.40 µT; electric field >0.42 V/m), however, the mean difference in testosterone levels between the three different groups of exposure wasn't statistically significant (P > 0.05). According to the results of Logistic Regression, the electric field had the greatest effect on testosterone levels as the main male hormone. Drawing a definitive conclusion regarding the effects of each harmful physical hazards is difficult due to the existence of psychological stressors and other environmental stressors such as chemical pollution, ergonomic hazards and other physical stressors.

Assessment of sexual functions in male patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea is characterized by repetitive cessation of breathing during sleep. It affects different aspects of sexuality. We aimed to assess male sexual function & risk factors in obstructive sleep apnea patients. METHODS: This case control study included 2 groups, 45 healthy volunteers as control group and 45 patients with confirmed diagnosis of obstructive sleep apnea. All the participants were subjected to measurement of Body Mass Index, Full night polysomnography (only for patients group) and serum total testosterone, FSH and LH. The International Index of Erectile Function-5 and Hamilton Depression Scale questionnaires were filed out for all participants. RESULTS: The mean scores for all sexual domains were significantly lower among the patients group compared to the control group (p<0.01). The Hamilton score was significantly higher among the patients group compared to the control group (p<0.0001). The mean levels of Testosterone and LH were significantly lower among the patients group compared to controls (p<0.0001), There were significant correlations between disease severity and age (r=0.48, p=0.001), Body mass index (r=0.48, p=0.001), Hamilton score (r=0.34, p=0.014) International Index of Erectile Function 5 domain score (r= -0.29, p=0.045)Testosterone level (r= -0.29, p=0.046) and LH levels (r= -0.104, p=0.049). CONCLUSION: We found that all domains of sexual function have been affected in patients group than controls. Their score was inversely related to the disease severity; which in turn has a complex interaction with other factors like age, obesity, hormones and psychological status. So when evaluating those patients, sexual dysfunction should be considered and assessed along with these factors.

A Novel Fertility Indicator Equation Using Estradiol Levels for Assessment of Phase of the Menstrual Cycle.

Background and Objectives: Urinary hormone home monitoring assays are now available for fertility awareness methods (FAMs) of family planning, but lack sensitivity and precision in establishing the start of the fertile phase. We hypothesized that with a suitable algorithm, daily serum or blood estradiol (E2) levels could serve as a better analyte to determine the phase of the ovulatory cycle and the fertile start day (FSD). Materials and Methods: Published day-specific serum E2 levels, indexed to the serum luteinizing hormone (LH) peak, were analyzed from three independent laboratories for a threshold for a FSD. A fertility indicator quation (FIE) was discovered and tested with these data and a FSD was determined using the mean or median and variance ranges of the day-specific E2 data. Results: The considerable variance of day-specific serum E2 levels made an absolute serum E2 indicator for phase of cycle problematic. However, a FIE was discovered which maps the day-specific E2 levels of the ovulatory cycle enabling the fertile phase and transition to the luteal phase to be signaled. In this equation, FIE(D) is the value of FIE on day, D, of the cycle and has both a magnitude and sign. The magnitude of FIE(D) is the product of the normalized change in day-specific E2 levels over two consecutive intervals, (D-2, D-1) and (D-1, D), multiplied by 100, and is formulated as: (E2 (on D-1) - E2 (on D-2))/E2 (on D-2) × (E2(on D) - E2 (on D-1))/E2 (on D-1) × 100. The sign of FIE(D) is either + or - or ind (indeterminate) and is assigned on the basis of the direction of this product. Using a FIE threshold of ≥2.5 as the start of the fertile phase, the FSDs were Day -5 or Day -6, with FSD Day -4 for an outlier set of E2 levels. The maximum FIE value ranged 9.5-27.8 and occurred most often on Day -2. An inflection point with a large change in FIE magnitude and change in sign from + to - always occurred at Day 0 for all sets of day-specific E2 data signaling transition to the luteal phase. Conclusions: The fertility indicator equation, a product of two sequential normalized changes in serum E2 levels with a sign indicating confidence in direction of change, is powerful in identifying the fertile phase and subsequent transition to the postovulatory phase and may serve as a useful algorithm for FAMs of family planning.