Follicle-stimulating Hormone Measurements Research Articles

O-013 Population pharmacokinetics of follitropin delta during ovarian stimulation

Abstract Study question Which patient characteristics affect serum follicle stimulating hormone (FSH) concentrations in women undergoing ovarian stimulation (OS) with follitropin delta, a human cell line derived FSH? Summary answer Body weight is the main determinant of serum FSH concentrations during OS. Renal function, race, ethnicity, hepatic function and age have at most small influence. What is known already The pharmacokinetics of FSH have been studied in dedicated studies with serial blood sampling, typically conducted in healthy subjects. Such studies are designed to provide detailed pharmacokinetic profile information but lack the statistical power for identifying individual patient characteristics affecting FSH exposure. Population pharmacokinetic modelling enables evaluating the influence of patient characteristics based on few FSH measurements per patient if data from many patients are available. Study design, size, duration Serum FSH concentrations were assessed by immunoassay in seven randomized, controlled, blinded, multicentre trials of follitropin delta in women undergoing an assisted reproductive technology program. The trials were conducted in the United States, Canada, Europe, Brazil, and Asia. In all, 2,721 women treated with follitropin delta contributed to the evaluation with 6,952 FSH measurements. Participants/materials, setting, methods FSH concentrations were described with a pre-specified one-compartment population pharmacokinetic model. The key model parameters were the apparent total clearance (CL/F) of follitropin delta, the interindividual variability in CL/F and the effects of baseline values of body weight, age, race, ethnicity, renal and hepatic function on CL/F. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and hepatic function by alanine transaminase (ALT) and bilirubin levels. Main results and the role of chance Area under the FSH concentration-time curve during a dosing interval (AUC) was derived from dose and CL/F. Body weight had the most pronounced effect on AUC, both in terms of effect magnitude and statistical significance. AUC was 1.28-fold higher (90% confidence limits: 1.25; 1.30) in women with a body weight of 47 kg (5th percentile) compared to women with a median body weight of 62 kg. The effect estimates of eGFR, Asian race and Black race on CL/F were within the bioequivalence limits of 0.80 and 1.25, but with 90% confidence limits not including a value of 1. The effect of Black race was estimated to be a 1.19 fold (90% confidence limits: 1.12; 1.26) higher AUC, as compared to White race. Despite this, the individual estimates of AUC were close to identical comparing these patient populations (mean (SD) relative to a typical study participant: 1.00 (0.25) and 0.97 (0.23), respectively). This is likely due to the mean body weight being higher in Black trial participants compared to White trial participants (78.3 kg compared to 68.2 kg). The effects of age, ethnicity and the hepatic function markers ALT and bilirubin were well within the bioequivalence range of 0.80 – 1.25. Limitations, reasons for caution Potential effects of subject characteristics on PK parameters such as subcutaneous absorption rate or volume of distribution could not be evaluated due to the number of serum FSH concentration measurements available per patient. Wider implications of the findings After follitropin delta administration, serum FSH concentrations are inversely related to body weight; this may be helpful for determining whether there is a need to consider body weight when selecting dose. Trial registration number NCT01426386, NCT02309671, NCT01956110, NCT03228680, NCT03296527, NCT03740737, NCT03738618, NCT03809429

P-697 The effect of smoking and vaping on hormonal ovarian reserve markers in women of reproductive age in the United Kingdom

Abstract Study question What impact do smoking and vaping have on ovarian reserve markers Anti-Mullerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH)? Summary answer Smoking and vaping negatively affect AMH and FSH levels in women, with significant age-related differences in ovarian reserve markers observed. What is known already Previous studies have established a link between smoking and accelerated ovarian follicular depletion, evidenced by lower serum AMH levels and reduced antral follicle count (AFC). Smoking is known to increase FSH levels indirectly by affecting pituitary function. However, the impact of vaping, a growing trend especially among younger individuals, on ovarian reserve markers like AMH and FSH remains under-researched and requires comprehensive investigation to understand its full implications on reproductive health. Study design, size, duration This cross-sectional study analysed medical history and serum AMH and FSH concentrations from capillary blood samples of 8,340 women aged 21-45. Participants were stratified by 5-year age intervals and excluded if they had reproductive health conditions or used hormonal contraception. Samples were analysed from individuals using an at-home hormone testing service, with statistical analysis including unpaired t-tests and Cohen’s d for effect size, focusing on smokers/vapers versus non-smokers/non-vapers. Participants/materials, setting, methods The study included UK women aged 21-45 providing capillary blood samples for serum AMH and FSH measurement using an at-home testing service. Exclusions applied to those with reproductive conditions or on hormonal contraception. Smoking and vaping status were self-reported through an online health assessment. AMH and FSH concentration differences were analysed via unpaired t-test; a p-value of < 0.05 was considered statistically significant and mean values±SD were reported. Main results and the role of chance Among 8,340 participants, 312 smoked and 653 vaped. Lower serum AMH values were observed in smokers and vapers in all age groups, with significant differences at ages 31-35 for smokers (20.73±16.23 vs 25.37±19.80 pmol/L in smokers and non-smokers respectively; p = 0.003) and 36-40 for vapers (13.65±13.34 vs 16.88±14.32 pmol/L in vapers and non-vapers respectively; p = 0.01). No significant differences in serum FSH concentration were found among vapers, however, FSH levels were higher in smokers across all ages. This was significant in individuals aged 21-25 (8.01±2.52 vs 6.87±3.33 IU/L in smokers and non-smokers respectively; p = 0.02) and 31-35 (8.33±3.31 vs 7.70±3.51 IU/L smokers and in non-smokers respectively; p = 0.04). These results suggest a detrimental effect of smoking and vaping on ovarian reserve markers, with statistical significance indicating the role of chance is minimal in the observed differences. Limitations, reasons for caution Self-reported smoking/vaping status may introduce bias. The study does not report the duration or frequency of participants’ smoking and vaping habits. The study’s cross-sectional design limits causality inference, however it provides a valuable insight for future longitudinal research to explore these relationships over time and explore underlying mechanisms. Wider implications of the findings These findings highlight the potential risks of smoking and vaping on women’s reproductive health, emphasising the need for awareness and preventive measures, especially among younger populations and the increased use of vaping. Trial registration number not applicable

P-733 Discrepancies between self-perceived and diagnosed cases of perimenopause - analysis of health data from 13,932 UK-based women

Abstract Study question Do individuals who self-reported “suspected perimenopause” in health assessments meet the diagnostic criteria for perimenopause, menopause or premature ovarian insufficiency (POI) based on clinical guidance? Summary answer Users were likely to experience more mood symptoms, compared to vasomotor symptoms or cycle irregularities and only 5.5% met the NICE perimenopause diagnostic criteria. What is known already An estimated 13 million individuals are currently experiencing perimenopause or menopause in the United Kingdom. The recent surge in media attention, while helpful in fostering awareness, may also carry the unintended consequence of leading individuals to self-identify with perimenopause without a clear understanding, due to the historical gap in comprehensive education on the subject. This study aims to investigate the prevalent symptoms reported by individuals who self-reported suspected perimenopause in a health assessment and assess whether these individuals meet diagnostic criteria for perimenopause, menopause or premature ovarian insufficiency (POI) based on clinical guidance. Study design, size, duration In this retrospective observational study, data was analysed from 13,932 users approaching women’s health testing services, citing “I think I am perimenopausal” as their reason for using the service between August 2022 and January 2024. We analysed data on age, menstrual cycle characteristics and symptoms self-reported via an online health assessment. A sub group analysis, done on 891 users aged 21-58, also analysed serum follicle-stimulating hormone (FSH) measured via immunoassay using a capillary blood sample. Participants/materials, setting, methods Among the 13,932 users, 8,101 (58.1%) were <40 years old, 4,947 (35.5%) were aged 40-45 and 884 (6.3%) were >45 years old. The dataset was compared with NICE criteria, stating that perimenopause/menopause is diagnosed in women >45 experiencing cycle irregularities and vasomotor symptoms, with the addition of two FSH measurements >30 IU/L to diagnose perimenopause/menopause or POI in those <45 or < 40 respectively. Main results and the role of chance The most frequently reported symptoms were fatigue 10,434 (74.9%), anxiety 8,526 (61.2%), irritability 8,361 (60.0%), depression 8,280 (59.4%), brain fog 7,898 (56.7%), headaches 6,483 (46.5%), hot flushes 5,289 (38.0%), hair thinning/loss 5,224 (37.5%), feeling cold often 4,999 (35.9%), night sweats 4,939 (35.5%), vaginal dryness 3,595 (25.8%) and pain during intercourse 3,525 (25.3%). In terms of menstrual cycle regularity, 7,515 (53.9%) had regular periods, 4243 (30.5%) selected irregular periods, 956 (6.9%) selected ‘I’m not currently/no longer getting periods’, 1195 (8.6%) selected ‘I don’t get periods because of contraception/HRT’. The subgroup analysis found that among users <40 years old, 1.2% (n = 6/524) would potentially fit the POI diagnostic criteria based on a single FSH measurement >30 IU/L, vasomotor symptoms and cycle regularity. Based on the same criteria, 2.9% (n = 8/279) of users aged 40-45 would be diagnosed with perimenopause/menopause and 39.8%(n = 35/88 ) of users >45 years old met the perimenopause/menopause criteria. However, of the total, only 5.5% (n = 49/891) of individuals who self-identified as perimenopausal met the NICE diagnostic criteria. Limitations, reasons for caution The online health assessment collects self-reported data, potentially influencing results. Subgroup analysis included individuals with at least 1 FSH test, however, guidelines advise 2 consecutive high FSH levels for perimenopause diagnosis, possibly reducing the number eligible for a potential perimenopause diagnosis. Wider implications of the findings Our data suggests users are most likely to experience mood symptoms, compared to vasomotor symptoms or cycle irregularities, which are required for a diagnosis. This spotlights the importance of including patient voices in clinical guidelines and the need for improved public awareness regarding perimenopause to promote healthcare-seeking behaviour for symptoms. Trial registration number NA

Development of external genitalia during mini-puberty: is it related to somatic growth or reproductive hormones?

Although hypothalamo-pituitary-gonadal axis is active during mini-puberty, its relationship with somatic growth and the role on the development of external genitalia has not been fully elucidated. We aimed to evaluate the effects of somatic growth and reproductive hormones on the development of external genitalia during mini-puberty. Anthropometric data, pubertal assesment, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), sex-hormone binding globulin (SHBG), estradiol (E2) and inhibin-B, testosterone (T), and anti-Mullerian Hormone (AMH) of healthy infants aged 1-4months were evaluated. Free sex hormone index was calculated as T/SHBG for boys and E2/SHBG for girls. The mean age of 148 (74 female) infants included in the study was 2.31 ± 0.76months. Tanner stage 2-3 sex steroid and gonadotropin levels were observed. A statistically significant difference was found between the weight, height, BMI, weight gain and serum FSH, LH, and A4 measurements of girls and boys (p < 0.05). Penile length was associated with weight (r = 0.24, p = 0.03), height (r = 0.25, p = 0.02), and AMH (r = 0.3, p = 0.01), but not with testosterone (p = 0.56 respectively). A negative correlation was found between weight and serum LH (r = - 0.26, p = 0.2) and T/SHBG levels in males (r = - 0.38, p = 0.015 respectively). Weight-SDS was negatively correlated with testosterone in males (r = - 0.25, p = 0.02). Testicular size and breast stage did not correlate with any of the hormonal and anthropometric parameters. Conclusions: External genitalia in males during mini-puberty is related more to somatic growth rather than reproductive hormones. Similar to pubertal developmental stages, both total and free testosterone are negatively associated with higher weight during mini-puberty. What is Known: • Mini-puberty allows early assessment of HPG axis function in infancy. • There is an inverse relationship between the amount of adipose tissue and circulating testosterone levels in males during puberty and adulthood. • The potential effect of somatic growth and reproductive hormones on external genital development during mini-puberty remains unclear. What is New: • During mini-puberty, males' external genitalia is more related to somatic growth than to reproductive hormones, but this relationship is not observed in girls. • Both total and free testosterone are negatively associated with higher weight during mini-puberty, similar to the pubertal developmental stages.

Concordance of hemoglobin A1c and reproductive hormone levels in menstrual and venous blood

ObjectiveTo explore whether menstrual blood collected via a modified menstrual pad is a surrogate for venous blood draw in analyzing HbA1c and fertility-associated hormones DesignCross-sectional study SubjectsStudy included 152 female participants who have regular menses, aged 19-50 years old. InterventionsParticipants collected menstrual effluent using a menstrual pad, modified with a removable dried blood spot (DBS) strip. Peripheral blood samples were collected by venipuncture within 60 hours of menstrual pad use. Main Outcome MeasuresMenstrual pad and venous blood draw samples were analyzed for levels of HbA1c, thyroid stimulating hormone (TSH), Follicle Stimulating Hormone (FSH), anti-Mullerian hormone (AMH), and Luteinizing hormone (LH). Correlation between menstrual pad and venipuncture samples was performed by Deming linear regression, and r coefficients were measured using Pearson correlation. ResultsInter-assay variability of menstrual pad DBS sample measurements was <6%. Menstrual HbA1c values were stabilized in the DBS strips through 53 days, and menstrual hormone levels remained stable through 15 days. Menstrual HbA1c levels were highly correlated with venipuncture samples (r=0.96). TSH (r=0.94), AMH (r=0.94), FSH (r=0.91), and LH (r=0.91) also showed high correlation between menstrual strip and venipuncture samples. ConclusionsHbA1c, TSH, AMH, FSH, and LH measurements in menstrual effluent showed high correlation to venous blood samples, supporting use of menstrual effluent as a surrogate sample for hormone testing.

Socioeconomic status is related to pubertal development in a German cohort

INTRODUCTION Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. OBJECTIVE The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. METHODS 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. RESULTS Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys' age at mutation. No significant differences in boys' and girls' serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. CONCLUSION Puberty onset/duration and boys' age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.

Antioxidant activity of purslane (portulaca oleracea l.) Leaf extract on ovarian oxidative stress levels and reproductive hormone levels of female white rats (rattus norvegicus) exposed to cigarette smoke

Purslane (Portulaca oleracea L.) is a wild plant that grows in Indonesia and is considered a weed, but the highest antioxidant activity was found in the leaves and stems. Cigarette smoke is one of the exogenous free radicals that can enter the blood circulation, so that it can interfere with all cells and tissues in the body, including the reproductive organs. The research that will be conducted is about the antioxidant effect of purslane leaf extract on oxidative stress levels, namely ovarian malondialdehyde levels and reproductive hormone levels, namely Follicle Stimulating Hormone (FSH) and 17ß-estradiol levels in female white rats exposed to cigarette smoke. This study is an experimental study with Randomized Post Test Only Control Group Design, using 24 female white rats aged 3 months weighing 200-250 g divided into 4 groups, namely the control group (K), the cigarette smoke group (P1), the purslane leaf extract group. (P2) and the group of cigarette smoke accompanied by purslane leaf extract (P3). Ovarian MDA measurement is a measurement of MDA levels as an indicator of oxidative stress in the ovaries determined by the spectrophotometry method. Measurement of FSH and 17ß-estradiol levels in blood taken intracardially through the right ventricle of the heart as measured by the ELISA method. The results showed that purslane leaf extract at a dose of 200mg/KgBW reduced ovarian MDA levels of female white rats exposed to cigarette smoke significantly with p-value &lt;0.05. However, there has been no significant change in FSH and 17ß-estradiol. Keywords: purslane leaf extract, cigarette smoke, Follicle Stimulating Hormone, 17ß-estradiol, malondialdehyde, health risk

Retrospective Monocentric Clinical Study on Male Infertility: Comparison between Two Different Therapeutic Schemes Using Follicle-Stimulating Hormone.

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs.

Comparative characteristics of endocrine profile in males with infertility as well as in adolescents with varicocele

Introduction. Male infertility poses a pressing issue due to escalating prevalence of males with reproductive system diseases, the most common among which is varicocele being diagnosed in childhood and adolescence. Measuring level of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol is the key element while assessing the reproductive male potential.Aim: to compare the parameters of hormonal status in adolescents with varicocele as well as males with diagnosed infertility and identify predictors of hypogonadism in pubertal period.Materials and Methods. Males with diagnosed infertility as well fertile males underwent a single measurement of serum FSH, LH, testosterone and estradiol levels. Adolescents with/without varicocele were measured the serum hormones noted above in dynamics annually between studies for the period within the 14 to 17 years of age. The data obtained were compared in infertile and fertile males, adolescents with/without varicocele, as well as assessed hormone status between different age groups in both cohorts and adolescents aged 17 years.Results. Our study allowed to identify significant differences in hormone level in male patients with infertility and varicocele lacking reproductive pathology. Infertile males had significantly higher levels of LH and estradiol (for both: p &lt; 0.001). The LH level in infertile vs. fertile males was 5.01 ± 2.69 IU/L vs. 3.40 ± 1.17 IU/L, respectively, whereas estradiol level was 136.51 ± 92.79 pmol/l and 82.49 ± 48.33 pmol/l, respectively that might indicate at lowered testosterone level. Fifteenand sixteen-year-old-adolescents with varicocele had significantly lower LH level: 15 years old – 3.72 ± 1.92 IU/L vs. 2.71 ± 1.65 IU/L (p &lt; 0.0123) in subjects without vs. with varicocele; 16 years old – 3.42 ± 1.16 IU/L vs. 2.81 ± 1.66 IU/L (p &lt; 0.0381) in subjects without vs. with varicocele. It may account for decreased testosterone level. Active puberty in adolescents is accompanied by dynamically increased testosterone levels. Starting from the age of 15 years, adolescents with varicocele had significantly increased testosterone level in each subsequent age group. Thus, at 14 and 15 years of age, testosterone level in adolescents with varicocele was 10.61 ± 4.70 nmol/l and 13.60 ± 5.64 nmol/l (p &lt; 0.0001), respectively, whereas at 16 and 17 years of age it continued to rise reaching 16.65 ± 6.44 nmol/l (p &lt; 0.001) and 19.22 ± 7.36 nmol/l (p &lt; 0.0160), respectively. In contrast, age-matched adolescents without varicocele had significantly elevated testosterone level solely at age of 15 vs. 14 years. Whereas at 14 years of age testosterone level in comparison group was 15.73 ± 7.2 nmol/l, at 15 years of age it was significantly increased up to 21.45 ± 9.51 nmol/l (p &lt; 0.0113). In the subsequent age categories of this group, no significant difference in testosterone level was found. While comparing such parameter between the main and control adolescent groups, testosterone level was significantly higher in adolescents lacking varicocele at the age of 14, 15 and 16 years compared with age-matched subjects with varicocele. At 14 years of age, testosterone level in adolescents without/with varicocele was 15.73 ± 7.2 nmol/l vs. 10.61 ± 4.7 nmol/l (p &lt; 0.0007), respectively, at 15 years of age – 21.45 ± 9.57 nmol/l vs. 13.60 ± 5.64 nmol/l (p &lt; 0.0001), respectively, at 16 years of age – 20.02 ± 5.84 nmol/l vs. 16.65 ± 6.44 nmol/l (p &lt; 0.0268), respectively. The FSH level in infertile males and adolescents with varicocele was 5.16 ± 2.67 IU/L and 4.1 ±2.63 IU/L (p &lt; 0.0081), whereas LH level was 5.01 ± 2.69 IU/L and 2.76 ± 1.65 IU/L (p &lt; 0.04), respectively. In adolescents with varicocele and infertile males, estradiol level was 177.45 ± 70.63 pmol/l and 136.51 ± 92.79 pmol/l (p &lt; 0.001), respectively. While comparing hormone levels in fertile males and adolescents lacking varicocele, a significantly higher estradiol level was found in adolescents 181,87 ± 27.14 pmol/l vs. 82.49 ± 48.33 pmol/l (p &lt; 0.001).Conclusion. A study of the hormonal status in infertile vs. fertile males revealed decreased testosterone production accompanied with higher levels of LH and estradiol. Due to profound changes in LH and testosterone levels detected in adolescents with varicocele as well as in infertile males, it is plausible that such hormones may serve as predictors of hypogonadism in the pubertal period. Adolescents with varicocele taking into consideration progressive course of the disease and verified lower testosterone level require further monitoring of hormone level to prevent endocrine infertility.

Socioeconomic Status Is Related to Pubertal Development in a German Cohort

Introduction: Current health literature suggests that there has been a decline in the age of pubertal onset and that pubertal onset/duration of puberty may, besides weight status, be influenced by socioeconomic context. Objective: The goal of this study was to determine whether pubertal onset/duration and puberty-triggering hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) vary according to socioeconomic status (SES). Moreover, we aimed to propose cutoff values of serum LH and FSH for predicting gonadarche in boys. Methods: 2,657 apparently healthy children and adolescents between 5.5 and 18 years from the area of Leipzig were recruited from the LIFE Child study. Age at pubertal onset/end of puberty was given in 738/573 children, respectively. Anthropometric parameters of puberty, blood measurements of LH and FSH, and questionnaires assessing SES were evaluated. Results: Lower SES was associated with earlier thelarche and longer duration of puberty in overweight/obese girls, whereas age of menarche was not affected. In boys with low SES, a trend versus earlier puberty onset can be seen. Lower SES was significantly associated with boys’ age at mutation. No significant differences in boys’ and girls’ serum levels of LH and FSH during puberty according to SES were observed. Serum LH levels of 0.56 IU/L and serum FSH levels of 1.74 IU/L showed the best prediction of gonadarche in boys. Conclusion: Puberty onset/duration and boys’ age at mutation is affected by SES. The proposed cutoff levels for serum LH and FSH could provide a serological tool to determine gonadarche in boys.

Proposed age-stratified reference intervals of FSH derived from normozoospermic men

Objective: To demonstrate that serum follicle-stimulating hormone (FSH) in men rises with age, and to explore FSH reference intervals of age-related partitioning.Methods: Men aged 20-50 years (n=1 190) underwent semen analysis according to World Health Organization (2010) methods. Serum was frozen prior to measurement of FSH by using the Siemens ADVIA Centaur® XP immunoassay system. FSH central 95% intervals after logarithmic transformation based on age were derived from 1 037 normozoospermic men. These were then applied to oligozoospermic and azoospermic men. Men producing azoospermic semen samples were further classified as having non-obstructive azoospermia by clinical diagnostic criteria, including genetic analysis and surgical exploration.Results: Serum FSH in normozoospermic men increased with age (P<0.05), and reference intervals were determined with 10-year brackets: 21-30 years [(1.0-8.2) IU/L], 31-40 years [(1.4-9.5) IU/L], 41-50 years [(1.9-12.0) IU/L]. The proportion of oligozoospermic men with normal FSH concentrations was less than the normozoospermic men, which in turn was lower among azoospermic men (both P<0.01). The azoospermic men were further broken down according to the nature of the azoospermia as either obstructive or non-obstructive azoospermia, and 86.4% (38/44) men with non-obstructive azoospermia had elevated serum FSH concentrations whereas only 6.7% (1/15) men with obstructive azoospermia had high FSH levels, and this was significantly different (P<0.01).Conclusions: FSH concentrations increase in men between 20-50 years, and clinical interpretation of serum FSH results in men must be made by using age-based reference intervals.

Assessment of ovarian function in adolescents and young adults after childhood cancer treatment-How accurate are young adult/parent proxy-reported outcomes?

Providers often rely on self-reported ovarian function in adolescent and young adult (AYA)-aged childhood cancer survivors when making clinical decisions. This study described reported menstrual patterns and the agreement between respondent-reported and biochemical premature ovarian insufficiency (POI) in this population. This was a cross-sectional study of survivors (or their parent proxy) aged 13-21.9 years who received gonadotoxic therapy and were enrolled in a longitudinal health survey. Participants reported menstrual regularity, hormone-replacement therapy (HRT) use, and ovarian dysfunction. Respondent-reported POI was defined as the survivor taking HRT for ovarian failure or having been told she had ovarian failure. Biochemical POI was defined as follicle-stimulating hormone (FSH) level ≥40 mIU/mL. The agreement between respondent-reported and biochemical POI was determined using Cohen's kappa coefficient (κ) and analyzed by demographic and clinical factors. Among 182 AYA-aged survivors (72.5% non-Hispanic White, 46.7% leukemia survivors), 14.8% reported requiring HRT to have menses but 55.5% reported regular menses without HRT use. Among survivors with FSH measurements (n=130), 17.7% reported POI whereas 18.5% had FSH ≥40 mIU/mL (κ=0.66, sensitivity 70.8%, specificity 94.3%). The highest agreement between respondent-reported and biochemical POI was with young adult self-report (κ=0.78) and survivors with >5 survivor clinic (κ=0.83) and/or >5 endocrinologist (κ=1.00) visits. The majority of AYA-aged survivors reported having regular menses without HRT support. The accuracy of respondent-reported POI increased with repeated survivor clinic or endocrinologist visits, highlighting the importance of continued education. Survivors must be informed about their ovarian function to enable them to advocate for their reproductive health.

Estradiol and Follicle-Stimulating Hormone as Predictors of Onset of Menopause Transition-Related Bone Loss in Pre- and Perimenopausal Women.

The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify pre- and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicle-stimulating hormone (FSH), measured in pre- and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a pre- or early perimenopausal baseline to 1 year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Women's Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (p < 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (p < 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiver-operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in pre- or early perimenopause than in late perimenopause. Tracking within-individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. © 2019 American Society for Bone and Mineral Research.

Association between vitamin D status and glycemic profile in postmenopausal women with type 2 diabetes

The aim of this study is to evaluate the association between vitamin D status and glycemic profile in postmenopausal women with type 2 diabetes. A cross-sectional study was carried out with 70 (59.47 ± 6.47 years; 1.56 ± 0.05 m; 73.56 ± 13.01 kg; 30.30 ± 5.00 BMI kg/m2) postmenopausal women with type 2 diabetes (T2D). The blood samples were collected after fasting for 12 h and the main outcome parameters were serum follicle-stimulating hormone (FSH), estradiol; 25-OH vitamin D; insulin; C-Reactive Protein; cholesterol total (CT), triglycerides (TG), high density lipoprotein (HDL-cholesterol), glucose; calcium, HDL-cholesterol. The average serum 25(OH)D level in this study was 28.45 ± 8.26 ng/mL. The prevalence of hypovitaminosis D was 60%. Table 1 displays mean and standard deviation values for participants’ characteristics. The postmenopause status of the women studied was confirmed by FSH and estradiol measurement. All the clinical and anthropometric characteristics did not show difference (p > 0.05) between the groups (Table 2). Triglycerides level was highest (p < 0.0391) in the hypovitaminosis D group. The other serum markers did not show statistical differences (p > 0.05) between the groups. In conclusion, our results suggest that only TG level shows a negative correlation with vitamin D status in postmenopausal women with type 2 diabetes.

Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial

SummaryBackgroundSperm selection strategies aimed at improving success rates of intracytoplasmic sperm injection (ICSI) include binding to hyaluronic acid (herein termed hyaluronan). Hyaluronan-selected sperm have reduced levels of DNA damage and aneuploidy. Use of hyaluronan-based sperm selection for ICSI (so-called physiological ICSI [PICSI]) is reported to reduce the proportion of pregnancies that end in miscarriage. However, the effect of PICSI on livebirth rates is uncertain. We aimed to investigate the efficacy of PICSI versus standard ICSI for improving livebirth rates among couples undergoing fertility treatment.MethodsThis parallel, two-group, randomised trial included couples undergoing an ICSI procedure with fresh embryo transfer at 16 assisted conception units in the UK. Eligible women (aged 18–43 years) had a body-mass index of 19–35 kg/m2 and a follicle-stimulating hormone (FSH) concentration of 3·0–20·0 mIU/mL or, if no FSH measurement was available, an anti-müllerian hormone concentration of at least 1·5 pmol/L. Eligible men (aged 18–55 years) had not had a vasovasostomy or been treated for cancer in the 24 months before recruitment and were able, after at least 3 days of sexual abstinence, to produce freshly ejaculated sperm for the treatment cycle. Couples were randomly assigned (1:1) with an online system to receive either PICSI or a standard ICSI procedure. The primary outcome was full-term (≥37 weeks' gestational age) livebirth, which was assessed in all eligible couples who completed follow-up. This trial is registered, number ISRCTN99214271.FindingsBetween Feb 1, 2014, and Aug 31, 2016, 2772 couples were randomly assigned to receive PICSI (n=1387) or ICSI (n=1385), of whom 2752 (1381 in the PICSI group and 1371 in the ICSI group) were included in the primary analysis. The term livebirth rate did not differ significantly between PICSI (27·4% [379/1381]) and ICSI (25·2% [346/1371]) groups (odds ratio 1·12, 95% CI 0·95–1·34; p=0·18). There were 56 serious adverse events in total, including 31 in the PICSI group and 25 in the ICSI group; most were congenital abnormalities and none were attributed to treatment.InterpretationCompared with ICSI, PICSI does not significantly improve term livebirth rates. The wider use of PICSI, therefore, is not recommended at present.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation Programme.

Revision de la técnica de la evaluación ultrasonografica de la reserva ovarica mediante el recuento de folículos antrales y el volumen ovarico promedio

La evaluación de la reserva ovárica es uno de los pilares fundamentales del diagnóstico de la pareja infértil. La medición de la hormona folículo estimulante (FSH) has sido considerada el gold stantard para dicha evaluación, sin embargo la evaluación ultrasonográfica (Recuento de folículos antrales y Volumen ovárico promedio) es una alternativa que tiene ventajas por su bajo costo y ser fácilmente reproducible desde el punto de vista técnico. El objetivo de este artículo es revisar y dar a conocer la técnica ultrasonográfica de la evaluación de la reserva ovárica con la finalidad de unificar criterios para su realización a nivel hospitalario.

Ultrasensitive Electrical Detection of Follicle-Stimulating Hormone Using a Functionalized Silicon Nanowire Transistor Chemosensor.

The follicle-stimulating hormone (FSH) is a hormone that belongs to a family of glycoprotein hormones. Determination of FSH can help in interpreting various factors that include physiology of the reproductive system, fertility maintenance, and identification or treatment of reproductive disorders. Sialic acids are derivatives of neuraminic acids with negative charges, present at the end of the sugar chains and further linked to the cell surfaces and glycoproteins. The direct measurement of FSH in a human body can be recorded by developing a sensor probe that responds particularly to sialic acids over the other hormones. However, existing diagnostic methods still suffer from many difficulties in terms of complicated handling techniques, expensive instrumentation, etc. Development of accurate, rapid, and low-cost FSH detection chemosensors is important to meet these demands. Herein, we utilized a novel sensing method for accurate and fast FSH detection using a metal-oxide semiconductor silicon nanowire field effect transistor (SiNW-FET) device. This is the first report to demonstrate the boronic acid-functionalized SiNW-FET device in FSH detection. FSH detection has been successfully determined using an assay buffer solution with 0.72 fM detection limit as well as using 20% serum with 1.1. fM detection limit. We also investigated the specificity with other gonadotropins/glycosylated serum proteins. The current measurements on FSH concentrations at different time intervals were also studied. The sensitive, cheap, and miniaturized SiNW-FET device can serve as an effective sensing approach for rapid screening of FSH and menopause diagnosis.

Evaluation of Sexual Function in Women with Hypogonadotropic Hypogonadism Using the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI).

BackgroundHypogonadotropic hypogonadism (HH), or secondary hypogonadism, results from reduced secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland, resulting in lack of production of sex steroids. The aim of this study was to evaluate self-reported sexual function in sexually active women with and without HH using two evaluation methods, the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI).Material/MethodsThe study recruited 88 women who attended an outpatient in vitro fertilization (IVF) clinic in Turkey for primary infertility, between August 2013 and August 2016. All patients were sexually active with an age that ranged from 20–41 years. Following an initial examination, including measurement of FSH and LH levels, all study participants were asked to complete the FSFI and BDI self-reporting questionnaires. Patients were divided into Group 1 (with HH) (N=42) and Group 2 (the control group) (N=46).ResultsAnalysis of the patient responses to questions regarding their sexual function in the FSFI and BDI showed that of the 42 patients in Group 1 (the HH group), 27 patients (64.28%) reported sexual dysfunction; of the 46 patients in Group 2 (the control group) 14 patients (30.34%) reported sexual dysfunction. Analysis of the FSFI lubrication scores and orgasm scores showed a statistically significant difference between the two groups (both, p<0.01).ConclusionsWomen with HH require both physical and psychological support to improve their sexual function, self-esteem, mental health, and quality of life.

Characterization of intra- and interpatient variability and trajectory of ovarian reserve measures in 121,737 women

Measures of ovarian reserve including basal antral follicle count (BAFC), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) are routinely utilized to counsel women undergoing fertility treatment or preservation. These measures also help in personalizing clinical protocols to minimize risks and optimize success rates, however, no large-scale study has been performed interrogating intra- or inter-individual variability in these metrics. To characterize variability and trajectory of ovarian reserve measures among a spectrum of women. We included 152,858 FSH, 330,266 BAFC, and 79,565 AMH measurements from 121,737 women at 13 fertility clinics (2000-2017). The mean number of FSH, BAFC, and AMH measurements per woman was 2.6, 3.1, and 1.3, respectively. Women were classified as UnknownFecundity if they used a sperm donor and had a female partner or no partner. Others were defined as FertilityTreatment or subgrouped based on diagnosis. We evaluated intra-individual variability of measurements within 3 months using the coefficient of variation (CV; standard deviation/mean) and used Kruskal-Wallis and Mann-Whitney Wilcoxon tests for difference of means between groups. We evaluated the relationship with age using a Generalized Estimating Equations (GEE) model with Poisson family (BAFC) or with Gaussian family (FSH, AMH), controlling for clinic and diagnosis. For trajectory models, we used GEE models controlling baseline age, clinic, and diagnosis. We also tested for interactions between time, age, and diagnosis. The intra-individual CV increased significantly with age for all three metrics, regardless of patient type. We saw greater variation in BAFC and AMH for FertilityTreatment, while FSH variation was greater for UnknownFecundity. For each metric within the FertilityTreatment diagnoses, the greatest variation was seen with diminished ovarian reserve (DOR), while the least was with polycystic ovary syndrome (PCOS). We next examined inter-individual variability among different patient groups. When we controlled for age and clinic, BAFC and AMH in UnknownFecundity, MaleFactor, TubalFactor, and UterineFactor both had similar values. Compared with UnknownFecundity, statistically significant differences in BAFC and AMH were found in DOR (BAFC 45% lower, AMH 1.3 ng/mL lower), Endometriosis (16% lower, 0.8 ng/mL lower), PCOS (50% higher, 3.3 ng/mL higher), and OvulatoryDysfunction (31% higher, 1.95 ng/mL higher). In contrast, for FSH, we only found differences in DOR (1.6 IU higher) and PCOS (1.4 IU lower), while UnknownFecundity was similar to other diagnoses in the FertilityTreatment group. Finally, we studied intra-individual rate of change of these metrics over time using trajectory modeling. We found that the rate of change increased with age, starting at age 30.0 for BAFC, 29.1 for AMH, and 25.9 for FSH. For subtypes, we found that the rate of change for FSH increased at a slower rate for PCOS and UnknownFecundity, compared with other diagnoses. Interestingly, we found that DOR patients had a slower rate of decrease in AMH compared with other patients. We found significant differences in variability and trajectory of ovarian reserve measures among women and at different ages. These findings underscore the importance of taking multiple factors into account when leveraging these markers in counseling and decision-making.

Simultaneous Measurements of Follicle Stimulating Hormone and Total Testosterone and Associations in Clinically Localized Prostate Cancer

Objectives: To evaluate the potential relations of simultaneous measurements of basal levels of follicle stimulating hormone (FSH) and total testosterone (TT) in clinically localized prostate cancer (PCa). Materials and Methods: The study included 126 patients who had simultaneous measurements of prostate specific antigen (PSA), FSH, and TT before undergoing radical prostatectomy for clinically localized PCa. Correlations and independent associations between clinical and pathological factors were investigated by statistical methods. Results: The tumor volume (TV) was directly correlated to PSA and TT which was inversely related to FSH. Moreover, it was independently associated with both PSA and TT. In a multivariate linear regression model, FSH and TV were simultaneous independent factors associated with TT, and the association was inverse in the former and direct in the latter. In the patient population, the subset with FSH levels above the third quartile was related to lower median levels of TT that were associated with high grade cancer showing a lower TV. In localized PCa, basal levels of TT were associated with tumor parameters and inversely related to FSH levels, and the subset FSH levels above the third quartile were related to lower TT levels that were associated with high grade cancers showing a lower tumor load. Conclusion: Preoperative TT was associated with tumor parameters and inversely related to FSH levels. Patient with increased FSH levels was related to lower levels of TT, which was associated with high grade cancer.