Median Follicle-stimulating Hormone Research Articles

Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.

MP30-11 DISTRIBUTION OF FOLLICLE STIMULATING HORMONE (FSH) LEVELS AMONG FERTILE AND SUBFERTILE NON-AZOOSPERMIC MEN

You have accessJournal of UrologyCME1 Apr 2023MP30-11 DISTRIBUTION OF FOLLICLE STIMULATING HORMONE (FSH) LEVELS AMONG FERTILE AND SUBFERTILE NON-AZOOSPERMIC MEN Solomon Hayon, Sai Kaushik S.R. Kumar, Xinlei Mi, Anthony Kang, Jasmine Lin, Daniel Greenberg, Robert Brannigan, and Joshua Halpern Solomon HayonSolomon Hayon More articles by this author , Sai Kaushik S.R. KumarSai Kaushik S.R. Kumar More articles by this author , Xinlei MiXinlei Mi More articles by this author , Anthony KangAnthony Kang More articles by this author , Jasmine LinJasmine Lin More articles by this author , Daniel GreenbergDaniel Greenberg More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Joshua HalpernJoshua Halpern More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003258.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While the clinical utility of FSH is well-established in the diagnosis and management of azoospermic men, the utility of FSH in non-azoospermic men is unclear. First, we characterized the distribution of FSH in fertile and subfertile non-azoospermic men. Second, we sought to determine an optimal FSH threshold that would distinguish between these groups. METHODS: We performed a retrospective analysis of men presenting for fertility evaluation between 2002 and 2020. Men with at least two semen analyses (SA) over a one-month period and one FSH level within 6 months of their index SA were included. Men with semen volume < 1.0cc, azoospermia, or men on hormonal medications were excluded. Men with at least one SA with total motile sperm count (TMSC) ≥ 20 million were classified as fertile, while men who had <20 million TMSC on both SAs were classified as subfertile. FSH was evaluated as an independent variable to determine a threshold that would predict fertility status. A multivariable logistic regression using dichotomized FSH with a broad range of FSH thresholds and other clinical variables was used to predict fertility status. We determined the area under the curve (AUC) for each FSH threshold via 5-fold cross-validation, repeated 1000 times. The optimal FSH threshold was selected according to the mean AUC. RESULTS: Among 1876 men, 1115 (59.4%) were fertile and 275 (14.7%) were subfertile. Age, varicocele, and testosterone were similar between groups. Median FSH was 4.00 vs 5.96 (p<0.001) among fertile vs subfertile men. AUC analysis was performed for FSH thresholds corresponding to the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentile FSH level for each cohort. While the FSH threshold of 5.6 had the highest AUC for prediction of fertility status (0.663), multiple additional thresholds ranging from 4.0 to 9.4 had very similar AUCs. Positive predictive value of FSH increased with higher FSH thresholds. CONCLUSIONS: This is the first large-scale study to characterize FSH values in non-azoospermic men. While there are significant differences in FSH among fertile and subfertile non-azoospermic men, no single FSH cutoff had high accuracy for prediction of fertility status. These findings suggest that the utility of FSH in non-azoospermic men may be greatest in identifying men with extreme FSH values, which may guide further clinical management. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e394 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Solomon Hayon More articles by this author Sai Kaushik S.R. Kumar More articles by this author Xinlei Mi More articles by this author Anthony Kang More articles by this author Jasmine Lin More articles by this author Daniel Greenberg More articles by this author Robert Brannigan More articles by this author Joshua Halpern More articles by this author Expand All Advertisement PDF downloadLoading ...

PD20-05 HIGH PREVALENCE OF HORMONAL ABNORMALITIES IN MEN WITHOUT OLIGOSPERMIA

You have accessJournal of UrologyCME1 May 2022PD20-05 HIGH PREVALENCE OF HORMONAL ABNORMALITIES IN MEN WITHOUT OLIGOSPERMIA Matthew Hudnall, Bailey Goyette, Minh Pham, Jeremy Lai, Justin Dubin, Richard Fantus, James Wren, Nelson Bennett, Robert Brannigan, and Joshua Halpern Matthew HudnallMatthew Hudnall More articles by this author , Bailey GoyetteBailey Goyette More articles by this author , Minh PhamMinh Pham More articles by this author , Jeremy LaiJeremy Lai More articles by this author , Justin DubinJustin Dubin More articles by this author , Richard FantusRichard Fantus More articles by this author , James WrenJames Wren More articles by this author , Nelson BennettNelson Bennett More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Joshua HalpernJoshua Halpern More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002558.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Newly updated male infertility guidelines from the American Urological Association recommend against universal hormone evaluation with measured levels of follicle stimulating hormone (FSH) and testosterone (T) in men with normal semen parameters due to prior limited data suggesting a low prevalence of abnormalities in this cohort. We sought to compare the prevalence of abnormal hormone parameters among men with and without sperm concentration abnormalities to determine the value of universal hormonal screening during fertility evaluation. METHODS: We retrospectively evaluated all men who underwent semen analysis (SA) and hormonal evaluation (morning serum T, FSH) at a large, integrated academic healthcare system between January 2002 and May 2021. Men were excluded if they had a prescription for T-modulating medications prior to index SA or if semen parameters were missing. Sperm concentration was dichotomized at 15 million/mL according to World Health Organization (WHO) criteria. Men with hormonal evaluation >1 year following index SA were excluded. We compared median and interquartile range (IQR) T and FSH levels according to sperm concentration using Kruskal-Wallis test. Differences in prevalence of low testosterone (<300 ng/dL) and abnormal FSH (>7.6 mIU/mL) were determined using Chi-square test. RESULTS: A total of 1,164 men had a morning serum T. There was no difference in median T among men with normal vs abnormal sperm concentration (316 ng/dL, interquartile range [IQR] 250-399 vs 316 ng/dL, IQR [253-419]; p=0.515). FSH level was measured in 1,261 men. Median FSH was higher among men with sperm concentration <15 million/mL (6 IU/mL, IQR 3.85-10.7 vs 3.8 IU/mL, IQR 2.7-5.7; p <0.001). Among men with ≥15 million/mL concentration, 44.1% were found to have low T (p=0.874) and 10.8% had an FSH ≥7.6 mIU/mL (p <0.001) (Table 1). Among men with ≥15 million/mL sperm concentration who underwent both T and FSH evaluation, 43.6% had at least 1 hormonal abnormality (Table 2). CONCLUSIONS: A large percentage of men with normal semen analysis had low T, challenging prior literature. As low T may have long-term implications for both fertility and overall health, providers should consider universal T screening in men presenting for fertility evaluation. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e357 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Hudnall More articles by this author Bailey Goyette More articles by this author Minh Pham More articles by this author Jeremy Lai More articles by this author Justin Dubin More articles by this author Richard Fantus More articles by this author James Wren More articles by this author Nelson Bennett More articles by this author Robert Brannigan More articles by this author Joshua Halpern More articles by this author Expand All Advertisement PDF DownloadLoading ...

Follicle-Stimulating Hormone (FSH) Levels During Androgen Deprivation Therapy Are Not Associated With Survival or Development of Castration-Resistant Prostate Cancer

Background Follicle-stimulating hormone (FSH) dysregulation plays a potential role in prostate cancer progression. The objective of this study was to evaluate whether higher FSH levels during androgen deprivation therapy (ADT) for recurrent prostate cancer could predict the development of castration-resistant prostate cancer (CRPC), prostate cancer-specific survival (CSS), and overall survival (OS). Methods Serum FSH levels were measured in cryopreserved samples of the continuous ADT arm of the PR.7 trial, supplemented with analogous samples from a large contemporaneous biobank. Univariate and multivariate analyses assessed the relationship between FSH tertiles and time to CRPC, as well as CSS, and OS. Results A total of 172 patients were included in our analysis. Of these, 54 patients (31%) developed CRPC during the 9-year follow-up. Median FSH for the tertiles was 4.35, 6.13, and 11.32 mIU/mL. FSH tertiles were not significantly associated with the time to CRPC, or with CSS or OS. FSH levels were not a significant prognostic factor for these oncologic outcomes. Conclusion As previously reported, the use of gonadotropin-releasing hormone (GnRH) antagonists for ADT has significantly more suppression of FSH levels than GnRH agonists. Our results do not suggest that differences in circulating FSH 1 year following ADT initiation influence long-term oncologic outcomes or development of CRPC.

Follicle-stimulating hormone in postmenopausal women living with HIV: a prevalence study.

ObjectivesWe examined follicle‐stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months’ amenorrhoea, and investigated correlation with menopausal symptoms.MethodsA cross‐sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months’ amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal–Wallis test.ResultsMedian age was 53 years [interquartile range (IQR): 51–55]; all were on antiretroviral therapy, three‐quarters (n = 65) had a CD4 T‐cell count > 500 cells/μL and 91.8% (n = 78) had an HIV viral load (VL) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1–78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T‐cell count ≥ 200 cells/μL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m2).Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37).ConclusionsFour women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2. We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months’ amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.

Clinical efficacy of two-staged Fowler-Stephens laparoscopic orchidopexy in the treatment of children with high cryptorchidism

Objective: To Evaluate the clinic effect of two-staged laparoscopic Fowler-Stephens orchiopexy in the treatment of high cryptorchidism, and compare it with laparoscopic orchiopexy treatment without disconnecting spermatic vessels. Methods: A retrospective analysis was conducted on 20 cases of children with high cryptorchidism who were treated with two-staged Fowler-Stephens orchiopexy from January 2015 to April 2019 (F-S group). All the children in this group had unilateral cryptorchidism, age 6 to 18 months. The average age was 13.5 months. Seven cases were on the left side, and 13 cases were on the right side. There were 20 control children in the same age group who were treated with testicular fixation without disconnecting spermatic vessels, age 6 to 18 months. The average age was 12.5 months. Six cases were on the left side, and 14 cases were on the right side. Testicular ultrasonography and sex hormone examination were conducted before operation. F-S group met the indications for Fowler-Stephens surgical. In the first stage, the testicular vessels were doubly clipped at a site away from the testis in laparoscopic, and the second stage was scheduled about 6 months after the first stage. The children in the control group were treated with laparoscopic orchiopexy without disconnect spermatic vessels. The two groups were followed up to 6 months after the operation, and the testicular volume and sex hormone indexes of the two groups were measured. The testicular volume and sex hormones before and after the operation of the F-S group and the control group were respectively subjected to a self-control study, and a hormone comparison study was carried out between the two groups of children. Results: Both the F-S group and the control group successfully fixed the testes in the scrotum without tension during the operation. In both groups, 20 cases of testicular positions were reexamined 6 months after the operation without retraction. All the patients had a viable testis in scrotum after operation. Two of F-S group had an atrophic testis in the scrotum, and the others had a good vascularization detected on echo color doppler ultrasound. The average testicular volume of F-S group was (0.34±0.16) ml before operation and the postoperative one was (0.38±0.13) ml, P=0.089, P>0.05. In control group, the preoperative average testicular volume was (0.40±0.14) ml, and postoperative one was (0.40±0.15) ml, P=0.933, P>0.05. The testicular volume of two group had no significant difference. Sex hormone reexamination: Testosterone (T), estradiol (E2) and luteinizing hormone (LH) did not change after operation. Prolactin (PRL) in F-S group was 13.44 μg/L before operation and 12.3 μg/L after operation, PRL in control group was from 15.45 μg/L to 10.34 μg/L, P=0.732, the change of prolactin (PRL) has no significant difference. The median preoperative follicle stimulating hormone (FSH) in the F-S group was 1.18 U/L preoperatively and 1.61 U/L postoperatively; the median FSH of the control group was 1.21 U/L preoperatively and 1.1 U/L postoperatively. Compared between the two groups, the postoperative increase in the FS group was higher than that before the operation, P=0.032, P<0.05, the difference was statistically significant. The median of progesterone (PROG) in the F-S group was 0.25 nmol/L before operation and 0.17 nmol/L after operation; the median PROG of the control group was 0.56 nmol/L before operation and 0.24 nmol/L after operation. It was lower after the operation than before the operation, P=0.034, P<0.05, the difference was statistically significant. Conclusions: (1) Laparoscopic Fowler-stephens staging operation is an effective method for the treatment of patients with high cryptorchidism, and it is worthy of further promotion. (2) Disruption of spermatic cord vessels does have an impact on hormones changes. The choice of this surgical procedure should be carefully and fully evaluated.

Ovarian reserve as a predictor of cumulative live birth

ObjectivesDevelop an up to date prediction model using recent cycle data and key pre-treatment predictor variables to estimate a couple’s individualised probability of a cumulative live birth after one cycle of ovarian stimulation and transfer of all frozen embryos, before the first embryo transfer. Study designThis was a retrospective cohort study. To estimate the cumulative live birth rate we only included couples who had used all embryos from their initial stimulation or achieved a live birth.We constructed a logistic regression model using live birth as a dependent variable and age group, duration of infertility, primary vs. secondary infertility, insemination method, cause of infertility, Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH) and antral follicle count (AFC) as our independent variables and used a backward elimination method to create the best fitting regression models to predict the probability of a cumulative live birth (p < 0.05 for elimination). ResultsThere were 516 complete cycles of ovarian stimulation resulting in 357 livebirths giving a cumulative livebirth rate of 69.2 % (95 % CI 66.0–74.0). Women with a live birth had significantly lower median age (34 years [IQR 31−37] vs. 36 years [IQR 33–39], p = 0.01) and FSH (6.7 iu/L [IQR 5.8−7.9] vs. 7.4 iu/L [IQR 6.2−8.6] and a significantly higher median AMH (22.1 pmol/L [IQR 12.1−30.9] vs. 10.5 pmol/L [IQR 7.3−20.7], p = 0.01) and AFC (18 [IQR 12−26] vs. 12 [IQR 9−19], p = 0.01). The backward conditional logistic regression model retained age category, FSH category and AMH category as significant independent predictors. The area under the curve for this model was 0.68 (95 % CI 0.63 – 0.73). ConclusionOur prediction model estimates a couple’s individualised probability of achieving a live birth after their first complete cycle of IVF using all known pre-treatment predictors. Limitations, reasons for cautionThe study population were only those eligible for NHS funded IVF treatment which have strict ovarian reserve criteria. Exclusion of those with very low egg reserve is likely to influence the predictive capacity of out model. Furthermore, our model was developed using cycle data from one unit and thus its predictive capacity has not been assessed on an independent cohort of women. We therefore welcome external geographical validation of our model prior to its use in clinical practice.

Total follicle stimulating hormone dose is negatively correlated with live births in a donor/recipient model with fresh transfer: an analysis of 8,627 cycles from the Society for Assisted Reproductive Technology Registry

Oocyte donation has optimized our understanding of ovarian stimulation. Increasing the follicle-stimulating hormone (FSH) dose has been shown to adversely affect live birth rates in autologous cycles. Our objective is to assess whether this relationship holds true within the donor/recipient population. Retrospective cohort study. Not applicable. Data from 2014-2016 included 8,627 fresh donor cycles. None. Live birth, clinical pregnancy, and miscarriage rates. The mean donor age ± standard deviation (SD) was 25.8 ± 2.8 years. Donors underwent a median of 16 days (interquartile range [IQR] 12, 19) of stimulation with a median (IQR) total FSH dose and daily dose of 2,350.0 (1,800.0, 3,025.0) and 153.8 (113.2, 205.0) IU, respectively. The live birth rate was 56.7% per transfer. For every 500-unit increase in FSH dose, there was a 3% reduction in the odds of a live birth (odds ratio [OR] 0.97; 95% confidence interval 0.95, 0.99), and a 3% reduction in the odds of a clinical pregnancy (OR 0.97; 95% confidence interval 0.95, 0.99). Days of stimulation and average daily dose were not significantly associated with live birth or clinical pregnancy. No significant association was found between miscarriage rates and total FSH dose, days of stimulation, or average daily dose. This is a novel report of a negative association of total FSH dosage on fresh IVF live births, performed in the donor population to control for oocyte source and endometrial receptivity.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia.

Prior studies have investigated sperm retrieval rates in men with nonobstructive azoospermia (NOA) secondary to specific etiologies, yet most cases of NOA are idiopathic. We compared sperm retrieval rates and testicular histopathology in idiopathic NOA (iNOA) and nonidiopathic NOA (niNOA). We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction (microTESE) between 2000 and 2016. Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic. Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology. Among 224 men, 86 (38.4%) were idiopathic, 75 (33.5%) were nonidiopathic, and 63 (28.1%) did not undergo genetic testing. Median age and serum testosterone were higher among iNOA or no testing versus niNOA. Median follicle-stimulating hormone (FSH) was lower among iNOA or no testing versus niNOA. A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele. Sperm retrieval rates were similar between iNOA, niNOA, and no testing (41.8% vs 48.0% vs 55.6%, respectively; P = 0.255). Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA (31.4% and 27.0% vs 16.0%, P = 0.073). On multivariable analysis, iNOA was not associated with sperm retrieval or spermatogenesis (P = 0.430 and P = 0.078, respectively). Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA. These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.

Effects of Radioactive Iodine Therapy on Ovarian Reserve: A Prospective Pilot Study.

Background: Thyroid carcinoma is the most common endocrine malignancy. Surgery is the standard therapeutic approach for patients with differentiated thyroid carcinoma (DTC), followed by radioiodine (RAI) therapy if indicated. For women with DTC, the effects of RAI therapy on gonadal and reproductive function are an important consideration. This study aimed to evaluate the effects of RAI therapy on ovarian function. Methods: A total of 33 premenopausal women were enrolled in this study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels during the early follicular phase were measured before and 3, 6, and 12 months after RAI therapy. The Friedman and Wilcoxon tests were used to detect changes in FSH, AMH, LH, and estradiol levels induced by RAI therapy over time. Results: The patients' ages ranged from 21 to 38 years, with a mean age of 31.15 ± 4.83 years. The median follow-up was 19 months (range 4-26 months). The median AMH levels were 3.25 ng/mL (range 0.32-17.42 ng/mL), 1 ng/mL (range 0.01-3.93 ng/mL), 1.13 ng/mL (range 0.08-6.12 ng/mL), and 1.37 ng/mL (range 0.09-6.1 ng/mL) before and at 3, 6, and 12 months after RAI therapy, respectively. The median FSH levels were 6.6 mIU/mL (range 3.78-15.5 mIU/mL), 5.83 mIU/mL (range 4.19-35.36 mIU/mL), 7.71 mIU/mL (range 4.24-16.25 mIU/mL), and 7.04 mIU/mL (range 4.93-19.96 mIU/mL) before and at 3, 6, and 12 months after RAI therapy, respectively. The AMH levels were higher before than after RAI therapy (p = 0.001). The AMH levels did not differ significantly between the three time points (p > 0.05). The FSH, LH, and estradiol levels were similar before and after RAI therapy (p > 0.05). Conclusion: AMH is considered an important marker of ovarian reserve. Ovarian reserve decreased after RAI therapy. More attention may be needed when considering RAI therapy for patients with reduced ovarian reserve.

The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency.

To evaluate the effect of 12-month DHEA supplementation on menstrual pattern and ovarian reserve markers in women with premature ovarian insufficiency (POI) METHODS: This is a prospective observational study. Women with POI were given DHEA supplements (25mg three times daily) for 12months. Sonographic assessment for ovarian volume and antral follicle count (AFC) and serum measurement for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol, testosterone, liver function, and hemoglobin level were performed at baseline and monthly for 13months after the supplementation. Menstrual pattern, ovarian reserve markers, and side-effects were recorded. Between August 2011 and July 2014, 38 women with POI were recruited and 31 completed the study. The median age of women was 36years, and the median baseline FSH and AMH concentrations were 82.2IU/L and 0.01ng/ml, respectively. No women had resumption of regular menstruation after DHEA supplementation. AMH, FSH, and AFC did not change significantly. No serious side effects were reported. Our results do not support any significant improvement in ovarian function by 12-month DHEA supplementation in women with POI.

Is there a difference in testosterone levels and its regulators in men carrying BRCA mutations?

BackgroundMale BRCA mutation carriers are at risk for an early onset aggressive prostate cancer. No data exist on the association of testosterone levels among these patients. We aimed to analyze testosterone and associated hormonal levels among male BRCA carriers and non-carriers.Patients and methodsOverall 87 male carriers and 43 non-carriers aged 40-70 were prospectively enrolled. Clinical data were collected and all patients were tested for total testosterone (TT), prostate specific antigen (PSA), follicle stimulating hormone (FSH), luteinizing hormone (LH), free androgen index (FAI), sex hormone binding globulin (SHBG) and prolactin. Multivariate linear regression analysis was performed to predict TT levels.ResultsThe median age, mean BMI, comorbidities, PSA, FSH, LH and SHBG levels in both groups were similar. However, mean TT and FAI were higher in the carriers (16.7 nmol/l vs 13.5 nmol/l, p=0.03 and 39.5 vs 34.8, p=0.05, respectively), while prolactin was significantly lower. Multivariate analysis demonstrated that while BMI was inversely correlated to TT levels in both groups, LH was a predictor only in non-carriers.ConclusionsCarriers have higher TT and FAI levels and lower prolactin levels; but LH does not predict their TT levels. Further research in a larger cohort of BRCA carriers with and without prostate cancer should be performed.

Smoking, alcohol and caffeine in relation to two hormonal indicators of ovarian age during the reproductive years

ObjectiveTo examine whether or not cigarette smoking, alcohol and caffeine intake are related to two indicators of ovarian age–anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH). Study designCross-sectional study of 477 women with a recent index spontaneous abortion (SA) (105 trisomic, 93 non-trisomic) or livebirth (LB) (279) with hormones measured on days 2–4 of an apparently normal menstrual cycle after the index pregnancy. ResultsCurrent smoking is associated with about a 15% increase in median FSH (β for ln(FSH)=0.14, 95% CI 0.03,0.25). It is not significantly related to AMH (β for ln(AMH)=−0.25, 95% CI −0.56,0.06). Neither alcohol 2–7days per week nor caffeine 122–<553mg per day is independently related to AMH or FSH. ConclusionsThe observation that current smoking is associated with FSH, but not with AMH, suggests that current smoking either impairs the development of antral follicles or dysregulates the hypothalamic–pituitary–ovarian axis. The absence of an association with AMH argues against mechanisms related to accelerated follicle atresia.

G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk.

The G-protein-coupled estrogen receptor (GPR30, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants' leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer's exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population.

Ovarian reserve is preserved in Behçet's disease.

To compare ovarian reserve with anti-müllerian hormone (AMH) levels, antral follicle counts (AFCs) and ovarian volume in patients with Behçet's disease (BD) and healthy subjects. This study included 35 women with BD (mean age: 34.4±5.3years) and 35 healthy controls (mean age: 34.1±6.0years). Venous blood samples collected from groups on menstrual cycle Days 2-4 were analyzed using the enzyme-linked immunosorbent assay to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2 ), prolactin (PRL) and AMH levels. The AFCs and ovarian volumes were estimated by ultrasonography on the same day. The body mass index (BMI), duration and severity of the disease, medications, and number of children were recorded. There was no statistically significant difference in the mean age, median gravida/para/abortus and the number of live births and mean BMI between the patient and control groups (P>0.05). No statistically significant difference in the median FSH, LH, E2, PRL levels, right and left ovarian volumes, and right and left ovarian AFCs was observed among the patients and the controls (P>0.05). There was no statistically significant difference in the mean AMH levels (P=0.468). Bonferroni correction showed no statistically significant correlation between AMH levels and age, BMI, FSH, LH, E2, PRL levels, right and left ovarian AFCs, right and left ovarian volume (P>0.025) among the controls and the patients. Our study results suggest that ovarian reserve is preserved in patients with BD. In addition, AMH levels of the BD patients were similar to levels of healthy subjects.

Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (β = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (β = 71.08, P = 0.006), and BMI before treatment (underweight: β = -59.93, P = 0.05; overweight: β = -40.62, P = 0.041). Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

Intermediate CGG repeat length at the FMR1 locus is not associated with hormonal indicators of ovarian age

Premutation and intermediate CGG repeat length at the fragile X mental retardation 1 (FMR1) locus have been associated with premature ovarian failure. We tested whether intermediate length is associated with indicators of ovarian age in a sample of fertile women. Our primary measures of ovarian age were antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels. The cross-sectional sample comprised 258 women with karyotyped spontaneous abortions (140 trisomic spontaneous abortions and 118 chromosomally normal spontaneous abortions or spontaneous abortions with anomalies other than trisomy) and 325 women with recent live births (LBs). We analyzed data from the total sample and data from LBs only. We defined CGG repeat length by the length (both continuous and categorical) on the longer allele. CGG repeat length was not significantly associated with either hormone measure. A repeat length of 35 to 54 CGG, versus the modal category of 30 CGG, was associated with an approximately 7% increase in median AMH level and a 3% increase in median FSH level. Results were unaltered when analyses were limited to LBs. Analyses of hormone levels using cutpoints to define older ovarian age showed no associations with repeat length. Among 10 women with repeat lengths of 35 to 54 CGG analyzed for AGG sequences, the uninterrupted CGG length was not significantly longer among women with hormonal indicators of "old" versus "young" ovarian age. Our data do not support an association between intermediate CGG repeat length and levels of AMH or FSH among fertile women.

Study On The Fertility Status Of Females With Primary Mediastinal B-Cell Lymphoma Following Treatment With Dose-Adjusted EPOCH-Rituximab

BackgroundIn young females with lymphoma, the impact of immunochemotherapy on fertility status has been poorly studied. Primary mediastinal B-cell lymphoma (PMBL) predominantly affects young females and is highly curable with the dose-adjusted EPOCH-rituximab (DA-EPOCH-R) regimen (Dunleavy et al., NEJM 2013:368;1408). We therefore identified this group of PMBL patients as an excellent population to study fertility status and evaluated the impact of DA-EPOCH-R on gonadal function of females aged 50 years or less. MethodsA questionnaire was first mailed to 27 patients, and this was followed by a semi-structured phone interview to obtain information on patients' medical and gynecologic/obstetric histories before PMBL diagnosis, during treatment and after its completion. Serum estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were analyzed before commencing chemotherapy, following 5-6 cycles of DA-EPOCH-R, and 10-18 months after treatment completion. ResultsAll patients included in the study completed 6-8 cycles of DA-EPOCH-R and were in complete remission from PMBL at a median follow-up of 63 months. Median age at diagnosis was 30.5 years (r 21-50). Twenty-three patients participated in the questionnaire. Prior to chemotherapy, twenty of twenty-three were menstruating, three patients were not. Of the twenty menstruating patients treated with DA-EPOCH-R three were unsure of their menstrual histories during chemotherapy, fourteen (70%) developed amenorrhea and three (15%), all younger than 25 years, continued to menstruate. After completion of chemotherapy, fifteen of the twenty patients (75%) had menstrual periods. All were 35 years or younger. Five patients (25%) remained amenorrheic following completion of chemotherapy, however one had a hysterectomy shortly after treatment completion. To date six of twenty (30%) patients have conceived naturally and delivered healthy children with nine not yet desiring motherhood.On laboratory evaluations performed before treatment, after 5-6 cycles of DA-EPOCH-R and 10-18 months after completion of chemotherapy, median serum LH levels were 2.5, 33.4 and 4.6 U/L respectively, median FSH values at the same time points were 3.6, 69.5 and 8 U/L, while median E2 levels were 24.4, <5 and 16.7 pg/mL, time courses consistent with transient ovarian damage from chemotherapy, but with recovery at a median follow-up of 12 months. Eight patients, who were 40 years or older were treated with DA-EPOCH-R. The median endocrine laboratory parameters of six of these patients, who had clinically normal ovarian function prior to treatment were examined at the indicated time points and were as follows: LH: 2.6, 36.4, 26.7 U/L; FSH: 6.4, 102.8, 83.9 U/L; E2: 68.8, <5, <5 pg/mL, a pattern consistent with premature menopause. ConclusionFertility appears to be preserved in female PMBL patients receiving DA-EPOCH-R, particularly in those less than 40 years old. The risk of premature menopause seems to be confined to patients over 40 years of age. Further analysis of ovarian reserve in patient younger than 40 years, measuring Anti-Muellerian hormone and inhibin-B pre- and post-treatment, is ongoing. Disclosures:No relevant conflicts of interest to declare.

Antral follicle count predicts natural menopause in a population-based sample: the Coronary Artery Risk Development in Young Adults Women's Study.

The timing of menopause is associated with multiple chronic diseases. Tools that predict this milestone have relevance for clinical and research purposes. Among infertile women, a positive relationship exists between antral follicle count (AFC) and response to controlled ovarian hyperstimulation, a marker of ovarian reserve. However, an age-independent relationship between AFC and menopause has not been demonstrated. Thus, our objective was to evaluate the relationship between AFC measured in women aged 34 to 49 years and incident natural menopause during 7 years of follow-up. The Coronary Artery Risk Development in Young Adults Study is a longitudinal community-based study (Chicago, IL; Birmingham, AL; Minneapolis, MN; and Oakland, CA) begun in 1985-1986. In 2002-2003, the Coronary Artery Risk Development in Young Adults Women's Study measured follicle-stimulating hormone (FSH) levels and performed a transvaginal ultrasound protocol that included AFC (2-10 mm follicles on both ovaries). Incident natural menopause was assessed by surveys in 2005-2006 and 2009-2010. In our sample (n = 456), the median (interquartile range) AFC and FSH level were 5 (2-9) and 7.8 (5.6-11.0) mIU/mL, respectively, at a mean (range) age of 42 (34-49) years in 2002-2003. One hundred one women reported natural menopause by 2009-2010. In Cox models, current smoking, stable menses, FSH level higher than 13 mIU/mL, and AFC of 4 or less were independently associated with incident natural menopause. Compared with AFC higher than 4, those with an AFC of 4 or less were nearly twice as likely to have undergone menopause during 7 years of follow-up (hazard ratio, 1.89; 95% CI, 1.19-3.02) after adjustment for covariates. AFC has been found to be independently associated with natural menopause during 7 years of follow-up after controlling for other markers of ovarian aging.

Waiting for an elevated FSH – Too late a marker of reduced ovarian reserve?

To assess age at which median follicle-stimulating hormone (FSH) is elevated above 10 U/L. Fertility and ovarian reserve decrease over the 4th decade with evidence that sensitive markers such as anti-Mullerian hormone fall even earlier. Despite its limitations, a basal or day 2-3 FSH is commonly used to assess ovarian reserve with levels over 10 U/L often used as a cut-point for further investigations. Women referred to a community laboratory for 'hormone testing', including FSH and oestradiol (n = 40 254), were included in a retrospective analysis. Cases excluded were those with suppressed FSH (<1 U/L) who were likely on the oral contraceptive pill or pregnant and those with increased oestradiol (>500 pmol/L) who were likely approaching mid-cycle or pregnant. Remaining cases (n = 32 445) were analysed in five-year age bands for FSH median, mean, and 2.5 and 97.5 percentiles. Median FSH remained consistently low (≤5 U/L) in women ≤35 years of age and was 6 U/L in 35- to 40-year-olds. The mean FSH and 97.5 percentile increased steadily. The 97.5th percentile was 10 U/L or lower in women up to 30 years of age. Follicle-stimulating hormone is a late indicator of known reducing ovarian reserve, and in this study, median FSH did not increase over 10 U/L until >45 years of age. FSH levels >9 U/L were above the 97.5th percentile in those <25 years of age. If fertility is a concern, FSH levels persistently above age-specific medians in women under 40 years may prompt earlier follow-up with more sensitive tests for ovarian reserve.