Basal Serum Follicle-stimulating Hormone Levels Research Articles

Factors Associated with Ovarian Hyperstimulation Syndrome (OHSS) Severity in Women With Polycystic Ovary Syndrome Undergoing IVF/ICSI.

IntroductionAge, polycystic ovary syndrome (PCOS), low body mass index (BMI), high antral follicle count (AFC), increased anti-Muller hormone (AMH) levels, and elevated serum estradiol (E2) concentrations are risk factors for ovarian hyperstimulation syndrome (OHSS). However, data on the relationship between risk factors and OHSS severity in patients with PCOS are rare.ObjectiveThis retrospective study examined the risk factors for OHSS and their effect on OHSS severity in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).MethodThe records of 2,699 women were reviewed and included in this study. These women were diagnosed with PCOS during their first IVF/ICSI cycle between January 2010 and December 2017. We analyzed the association between each of the interrogated risk factors (including female age, BMI, AFC, basal serum E2, and the number of oocytes retrieved) and OHSS. The effects of each risk factor on OHSS severity were further explored. Logistic regression was performed as part of the above analysis.ResultsOf the 2,699 women with PCOS who underwent assisted reproductive technology (ART), 75.2% had a normal response to controlled ovarian hyperstimulation (COH), while 24.8% developed OHSS. All OHSS patients were younger and had lower BMIs and basal serum follicle-stimulating hormone (FSH) and E2 levels but higher AFCs than those in the normal group. AFC demonstrated a strong correlation with OHSS, with a cutoff value of 24 in patients with PCOS. A total of 19.5% of the patients had mild OHSS, while 80.5% had moderate OHSS. Compared with those in the moderate OHSS group, those in the mild OHSS group were older and had higher basal serum FSH levels and lower serum E2 and T levels. However, BMI and AFC were not different between the mild and moderate OHSS groups. Basal serum E2 showed a strong correlation with OHSS severity, with a cutoff value of 37.94 pg/ml.ConclusionsAFC is a strong marker of OHSS, and basal serum E2 is the best predictor of OHSS severity in women with PCOS undergoing IVF treatment.

Acupuncture for premature ovarian insufficiency: a systematic review and meta-analysis

To analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle-stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Mullerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane’s tool. Meta-analysis was conducted by RevMan version 5.3. Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=−5.82, 95%CI: −9.76 to −1.87, I2=82%, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95%CI: 0.34 to 1.52, I2=88%, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=−4.53, 95%CI: −8.96 to −0.10, I2=73%, P=0.04) and acupuncture plus HRT (MD=−9.60, 95%CI: −17.60 to −1.61, I2=50%, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95%CI: 1.03 to 1.82, I2=0%, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=−3.16, 95%CI: −9.41 to 3.10, I2=0%, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT. The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures

The aim of the present study was to evaluate the possible relationship between melatonin levels in the follicular fluid (FF) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive treatment. Sixty-three females (20 to 40 years old) scheduled for IVF were divided into three groups based on their antral follicle count (AFC). We determined FF melatonin concentrations in group A (AFC≦6, n = 21), group B (7≦AFC≦14, n = 22), group C (AFC≧15, n = 20) on oocyte retrieval day. Patients in group C had significantly higher melatonin levels as compared to patients in groups A and B (p < .001). Melatonin levels of the patients were significantly positively correlated with antral follicle count (AFC, p < .001), serum anti-Müllerian hormone(AMH) levels (p =.001), serum estradiol (E2) levels on human chorionic gonadotropin (HCG) administration day (p = .001), total follicle-stimulating hormone (FSH) dose (p = .002), starting FSH dose (p = .035), number of retrieved oocytes (p < .001), total fertilized oocytes (p < .001), normally fertilized oocytes (p < .001), cleaved oocytes (p < .001), number of high-quality day 3 embryos (p = .004), blastocysts obtained (p = .007) and total embryos obtained (day3 embryos + day5/6 blastocysts) (p = .005). The levels were significantly negatively correlated with age (p < .001), basal serum FSH levels (p = .003), serum FSH (p = .001) and serum luteinizing hormone (LH) levels (p = .003) on HCG administration day. This is the first demonstration of a significant positive correlation of melatonin concentrations with AFC in patients undergoing IVF. We propose that FF melatonin levels may influence the IVF outcomes.

Nomogram to predict the number of oocytes retrieved in controlled ovarian stimulation.

ObjectiveOvarian reserve tests are commonly used to predict ovarian response in infertile patients undergoing ovarian stimulation. Although serum markers such as basal follicle-stimulating hormone (FSH) or random anti-Müllerian hormone (AMH) level and ultrasonographic markers (antral follicle count, AFC) are good predictors, no single test has proven to be the best predictor. In this study, we developed appropriate equations and novel nomograms to predict the number of oocytes that will be retrieved using patients' age, serum levels of basal FSH and AMH, and AFC.MethodsWe analyzed a database containing clinical and laboratory information of 141 stimulated in vitro fertilization (IVF) cycles performed at a university-based hospital between September 2009 and December 2013. We used generalized linear models for prediction of the number of oocytes.ResultsAge, basal serum FSH level, serum AMH level, and AFC were significantly related to the number of oocytes retrieved according to the univariate and multivariate analyses. The equations that predicted the number of oocytes retrieved (log scale) were as follows: model (1) 3.21–0.036×(age)+0.089×(AMH), model (2) 3.422–0.03×(age)–0.049×(FSH)+0.08×(AMH), model (3) 2.32–0.017×(age)+0.039×(AMH)+0. 03×(AFC), model (4) 2.584–0.015×(age)–0.035×(FSH)+0.038×(AMH)+0.026×(AFC). model 4 showed the best performance. On the basis of these variables, we developed nomograms to predict the number of oocytes that can be retrieved.ConclusionOur nomograms helped predict the number of oocytes retrieved in stimulated IVF cycles.

Treatment of infertile women with unilateral tubal occlusion by intrauterine insemination and ovarian stimulation

ObjectiveThe aim of this study was to evaluate the value of intrauterine insemination (IUI) combined with ovarian stimulation in women with unilateral tubal occlusion detected on hysterosalpingography (HSG). Materials and MethodsA total of 703 patients undergoing IUI and controlled ovarian hyperstimulation were enrolled in this study. The study group consisted of 133 patients treated for unilateral tubal occlusion diagnosed by HSG during 2005–2011. The control group consisted of 570 patients with unexplained infertility treated during the same period. In all cases of the retrospective study, menstrual cycles were regular, basal serum follicle-stimulating hormone levels and sperm parameters were normal. ResultsThere were no significant differences in pregnancy rate per cycle between the study (17.3%) and control groups (18.9%). The pregnancy rate was higher in patients with proximal tubal occlusion (21.7%) compared with mid-distal tubal occlusion (12.5%) or unexplained infertility (18.9%), but the difference was not statistically significant. ConclusionsInfertile patients with only unilateral proximal tubal occlusion detected on HSG can be treated initially by IUI combined with ovarian stimulation. The cycle outcomes in patients with proximal tubal occlusion are similar to patients with unexplained infertility. However, the stimulated IUI might not be a good choice for patients with unilateral mid-distal tubal occlusion because of a lower success rate, although further evidence is needed.

Antral follicular count is a better indicator for the assessment of ovarian reserve

Objectives To assess the ovarian reserve using the antral follicular count (AFC) versus the basal serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), E2, and serum progesterone according to the ovarian response and the chemical pregnancy rate. Material and methods Eighty-six women undergoing Intra Cytoplasmic Sperm Injection or IVF for male factor, tubal factor, or unexplained infertility were studied using a long luteal phase protocol for induction of ovulation. All patients were subjected to measurements of basal serum FSH, E2, progesterone, and AMH and also assessment of AFC. The ovarian response was determined by the number of oocytes retrieved. The correlation between different tests and outcomes was determined. Results There was a significant statistical difference between the good and the poor responders in terms of the basal serum FSH level, serum AMH, and AFC (6.45±2.27 and 12.95±6.69 IU/ml), (0.692±0.819 and 0.227±0.505 ng/ml), and (11.76±5.3 and 5.71±3.3 follicles), respectively. Receiver-operator characteristic curve showed that both FSH and AMH have limited value in predicting the ovarian response, with a sensitivity and specificity of 9.26 IU/ml, 70 and 91.2%, likelihood ratio 7.927, and 0.11 ng/ml, 73.33 and 72.85%, likelihood ratio 2.7, respectively, but the AFC has a high value in predicting the ovarian response; the cut-off value, sensitivity, and specificity were 8, 85.71 and 73.46%, likelihood ratio 3.22. All the investigated tests showed limited value in predicting pregnancy. Conclusion All three basal serum FSH, AMH, and AFC seem to predict the ovarian reserve but the AFC is superior to FSH and AMH, and it is less invasive and cheaper.

Basal follicle stimulating hormone (FSH) level as a predictor of fetal aneuploidy in patients undergoing in vitro fertilization (IVF)

Increasing maternal age promotes embryonic aneuploidy and subfecundity whereas elevated serum levels of FSH predict subfecundity, regardless of age. It is unclear, however, whether rising serum FSH levels also predict poor oocyte quality leading to embryonic aneuploidy. Therefore, the objective of this study was to determine if basal serum FSH levels predict the risk of embryonic aneuploidy in women undergoing IVF, independent of age. Historical cohort study. Seventy-six patients undergoing 97 IVF cycles of preimplantation genetic screening (PGS) with comparative genomic hybridization (CGH) were studied. Basal serum FSH levels on cycle day 3 were assessed before initiation of hormone therapy. GnRH agonist and antagonist were used in 74% and 26% of the IVF cycles, respectively. Embryonic aneuploidy was calculated as a ratio of number of aneuploid embryos per total embryos biopsied on day 3. The association between log serum FSH level and embryonic aneuploidy rate was assessed by multiple linear regression, adjusting for maternal age, total gonadotropins used and maximal serum estradiol (E2) level. Mean maternal age, log serum FSH and log maximal serum E2 were 39 ± 3.5 years, 0.8 ± 0.26 mIU/mL and 3.49 ± 0.23 pg/ml, respectively. 3348 ± 1629 IU of total gonadotropins were used. Embryonic aneuploidy increased at a rate of 0.12 per year with maternal age. There was no significant correlation between log serum FSH level and embryonic aneuploidy rate, controlling for all covariables. There was a significant positive correlation between the interactions of peak E2 levels and maternal age with aneuploidy, which was thought to be secondary to the effect of maternal age. Despite the positive correlation between embryonic aneuploidy rate and maternal age, no relationship was evident between elevated basal serum FSH levels and genetic quality of the embryo, as assessed with PGS with CGH.

The correlation between basal serum follicle-stimulating hormone levels before embryo cryopreservation and the clinical outcome of frozen embryo transfers

To evaluate the correlation between basal serum FSH level before the fresh IVF/intracytoplasmic sperm injection (ICSI) cycle and the clinical outcome of the subsequent frozen embryo replacement cycles. Retrospective observational study. University tertiary referral center, London, United Kingdom. Five hundred four consecutive frozen embryo transfer (FET) cycles where serum FSH levels were obtained, on days 1-4 of the cycle before the fresh IVF +/- ICSI cycles. Frozen-thawed embryo transfer. Clinical pregnancy (CP) and live birth (LB). Basal serum FSH in 127 women (25.2%) who had a CP was significantly lower compared with that in women who did not have a CP. Multivariate regression analysis showed significant correlation between basal serum FSH levels and clinical pregnancy and a low significance to LB, but there was no statistical significant differences between women who had a CP and those who did not with regard to age, treatment protocol (natural or hormone treatment cycle), or the freeze-thaw interval. The LB rate was higher in natural cycles (n = 71; 21.2%) than in hormone treatment cycles (n = 28; 16.7%). Conceiving in the fresh cycle had a positive influence on the FET outcome. Basal serum FSH level before fresh IVF/ICSI cycle is inversely correlated to a CP outcome in FET cycles. A trend was present between FSH levels and LB, but this failed to reach statistical significance.

Effects of Utero-ovarian Anastomoses on Basal Follicle-stimulating Hormone Level Change after Uterine Artery Embolization with Tris-acryl Gelatin Microspheres

To assess the prevalence of anastomoses between uterine and ovarian arteries on angiography and their impact on changes in basal follicle-stimulating hormone (FSH) level after uterine artery embolization (UAE). Consecutive premenopausal women who underwent UAE for symptomatic uterine leiomyomata according to a uniform embolization technique with tris-acryl gelatin microspheres at a single institution were included in the study. Basal FSH levels before UAE and 6 months after UAE were compared for patients with and without anastomoses between uterine and ovarian arteries on angiography. Among 124 patients included in the study (mean age, 43.1+/-5.7 years), patent anastomoses between the uterine and ovarian arteries were detected by angiography in 55 patients (44.4%). Overall, 11.3% of 124 patients showed an increase in basal serum FSH level of greater than 20 mIU/mL after UAE. In patients with utero-ovarian anastomoses, 18.2% showed an increase of greater than 20 mIU/mL after UAE, compared with 5.8% of patients without such anastomoses (P=.03). Mean basal FSH increase after UAE in patients with anastomoses was 8.4+/-20.2 mIU/mL, compared with 2.7+/-10.6 mIU/mL in patients without anastomoses (P=.047). Among patients with anastomoses, the 50- to 54-year age group had the highest percentage of patients with an FSH increase greater than 20 mIU/mL (50.0%) after UAE, followed by patients in the 45- to 49-year age group (15.4%). Angiographically detected anastomoses between the uterine artery and the ovarian artery are not uncommon. UAE in patients with anastomoses is associated with a greater risk of significant increase of basal FSH level than in UAE in patients without anastomoses. The pathophysiologic processes resulting in change of FSH level may be a reflection of diminished ovarian function, but further study is warranted to delineate the precise mechanism.

A preliminary study on reduced dose (33 or 25 μg) gonadotropin-releasing hormone agonist long protocol for multifollicular ovarian stimulation in patients with high basal serum follicle-stimulating hormone levels undergoing in vitro fertilization–embryo transfer

The aim of the present study was to evaluate the clinical efficacy of half-dose (50 μg) and further reduced dose (33 or 25 μg) gonadotropin-releasing hormone agonist (GnRH-a; triptorelin) long protocols for multifollicular ovarian stimulation (MFOS) for patients with high basal serum follicle-stimulating hormone (FSH) level undergoing in vitro fertilization and embryo transfer (IVF-ET). One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH (>10.0 mIU/ml) were included in this retrospective study. Study subjects were assigned to two groups: continuous half-dose GnRH-a long protocol (group A, n = 63) vs. further reduced dose GnRH-a long protocol (group B, n = 39) from half-dose at the start of GnRH-a to one-third or one-quarter dose after pituitary downregulation. Exogenous FSH or human menopausal gonadotropin was administered for MFOS in step-down mode, four or fewer embryos were transferred, and the outcomes of MFOS were compared between the two groups. Serum estradiol (E2) level on the day of human chorionic gonadotropin administration was significantly higher in group B (mean ± standard deviation (SD): 1318.3 ± 1120.4 vs. 2054.9 ± 1773.5 pg/ml, p = 0.015). The number of transferable and good-quality embryos was also significantly higher in group B (mean ± SD: 2.9 ± 1.7 vs. 3.7 ± 2.0, p = 0.027; 1.8 ± 1.4 vs. 2.7 ± 2.0, p = 0.020). No statistically significant difference in the outcomes was observed with respect to the dose of gonadotropins administered, the number of oocytes retrieved or the clinical pregnancy rate. In conclusion, GnRH-a long protocol with a reduced dose, tapered from the starting half-dose to a third or a quarter of the normal dose after pituitary suppression, may be beneficial for MFOS in IVF-ET patients with a high basal serum FSH level. A further prospective randomized controlled study on a larger scale is needed to confirm these findings.

Low pulse oxygen saturation in post-menopausal women at high altitude is related to a high serum testosterone/estradiol ratio

Objective: The present study was designed to determine if low pulse oxygen saturation ( Sp o 2) in post-menopausal women at high altitude was related to high serum testosterone/estradiol (T/E 2) ratio. Method: Studies were carried out in 191 women living in Cerro de Pasco, Peru (4340 m above sea level) and in 56 women living in Lima (150 m asl). Body weight, height, Sp o 2, hematocrit, serum follicle stimulating hormone (FSH), T and E 2 levels were measured in all women. Body mass index (BMI), menopausal status and serum T/E 2 ratio were calculated from data. Result: At high altitude, the values of Sp o 2, serum T, and serum E 2 were significantly lower in post-menopausal than in pre-menopausal women. Hematocrit, serum FSH levels, and serum T/E 2 ratios were significantly higher in post-menopausal women. Serum T and E 2 levels, T/E 2 ratio, Sp o 2, and hematocrit levels were not further changed with time after menopause. Women with Sp o 2<85% had lower serum E 2, a higher serum T/E 2 ratio, and higher hematocrit values than women with Sp o 2>90%. At high altitude, multiple regression analysis showed that low Sp o 2 was related to menopausal status (−2.6±0.83; β±S.E.; P<0.002) and not to chronological age (−0.06±0.04; P: NS). Further analysis showed that low Sp o 2 was related to high basal serum FSH levels and a high serum T/E 2 ratio in the presence of an interaction between FSH and T/E 2. Conclusion: Low values of Sp o 2 in women at high altitude were related to a high T/E 2 ratio.

Clinical usefulness of basal FSH as a prognostic factor in patients undergoing intracytoplasmic sperm injection.

To determine if basal serum follicle stimulating hormone (FSH) level could be a prognostic factor of the clinical outcome in intracytoplasmic sperm injection (ICSI) cycles in the couples with male factor infertility. From December 1995 to March 1998, total 118 patients underwent in vitro fertilization and embryo transfer (IVF-ET) with ICSI due to male factor infertility were included in this study. Patients were allocated to the low basal FSH group (< 8.5 mIU/ml) and the high basal FSH group (> or = 8.5 mIU/ml). The basal levels of FSH were measured in the 3rd day of menstrual cycle preceding ovarian stimulation cycle in total IVF cycles by immunoradiometric assay (IRMA). Statistical analysis was performed using Student's t-test, Fisher's exact test, and chi 2 test as appropriate. Statistical significance was defined as p < 0.05. The total dose of exogeneous gonadotropin required in the high basal FSH group was significantly higher than that in the low basal FSH group. The numbers of retrieved oocytes and oocytes with grade I, II were significantly higher in the low basal FSH group. The clinical pregnancy rate per cycle in the low basal FSH group (16.2%) was significantly higher than that in the high basal FSH group (4.0%). These results suggested that the basal serum FSH levels could be predictive of pregnancy outcome and the results of controlled ovarian hyperstimulation (COH) in ICSI cycles.

Inhibition of luteinizing hormone, follicle-stimulating hormone and sex-steroid levels in men and women with a potent antagonist analog of luteinizing hormone-releasing hormone, Cetrorelix (SB-75)

Cetrorelix (SB-75; [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] luteinizing hormone-releasing hormone (LHRH)) is a new highly potent antagonist analog of LHRH containing the D-ureidoalkyl amino acid D-citrulline at position 6 and is free of allergenic effects. This study shows the inhibition of LH and follicle-stimulating hormone (FSH) release in normal men, postmenopausal women and patients with gonadal dysgenesis, using different doses and i.m., s.c. and i.v. routes of administration of SB-75. The mean serum levels of LH and FSH in normal men who received one single dose of 300 micrograms of SB-75 sc started to decline rapidly 1 h after its administration; the LH suppression was sustained for 14 h and that of FSH up to 24 h or longer as the samples were obtained only up to this time. The nadir for LH was reached at 14 h and that for FSH at 24 h or later after administration of the antagonist (p < 0.05). Serum levels of total and free testosterone decreased after the first hour and this inhibition was maintained for up to 14 h. The nadir for total testosterone was at 6 h and that for free testosterone was at 8 h (p < 0.001), corresponding to 56% and 60% of inhibition, respectively. In postmenopausal women, inhibition of the elevated basal serum LH and FSH levels occurred after a single injection of the antagonist analog SB-75 in doses of 75, 150, 300, 600 and 1200 micrograms using im, sc and iv routes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vitamin A deficiency upon gonadotropin response to gonadotropin-releasing hormone.

There is a monotypic change in basal serum gonadotropin levels following retinol treatment of chronically vitamin A-deficient (VAD) male rats. The present study was undertaken to investigate the hypothesis that the specific increase in serum follicle-stimulating hormone (FSH) represents a change in gonadotrope responsiveness to gonadotropin-releasing hormone (GnRH). To this end, a test dose of GnRH was given to VAD rats pre-, 5 days post-, and 10 days postreplacement of vitamin A (PVA). In VAD rats, basal serum FSH and luteinizing hormone (LH) levels were higher than those of controls. Increased LH/testosterone ratios, both in basal levels and in the secretory response to GnRH, suggested Leydig cell hyporesponsiveness in VAD animals. Both the FSH and LH responses to GnRH were maximal at 1 h, declining thereafter. Although the absolute increments in FSH and LH 1 h after GnRH in VAD rats were greater than in controls, the percent increase in FSH tended to be lower in VAD rats and to increase after vitamin A replacement. The specific enhancement of FSH release PVA became evident only when assessing total secretion of FSH and LH after GnRH. Luteinizing hormone response to GnRH increased PVA, but not significantly, while FSH secretion after GnRH increased both 5 and 10 days PVA, times during which basal FSH levels were also increasing. These changes in FSH secretion could not be attributed either to increases in endogenous GnRH or to changes in testosterone or estradiol levels. Basal serum androgen binding protein levels, elevated in VAD animals, did not respond to the acute increases in FSH after GnRH and remained high PVA, suggesting no acute change in Sertoli cell function. Thus, the PVA increase in FSH secretion unmasks a partial inhibition of the gonadotrope present in the retinol-deficient, retinoic acid-fed male rat.

Selective release of follicle-stimulating hormone by 5 alpha-dihydroprogesterone in immature ovariectomized estrogen-primed rats.

The effect of 5 alpha-dihydroprogesterone (5 alpha-DHP) on gonadotropin release was examined in the immature acutely ovariectomized (OVX) rat primed with a low dose of estradiol (E2). Treatment with various doses of 5 alpha-DHP given in combination with E2 increased levels of follicle-stimulating hormone (FSH) but had no effect on serum luteinizing hormone (LH). A single injection of a maximally stimulating dose of 5 alpha-DHP (0.4 mg/kg) stimulated increases in serum FSH at 1200 h and, 6 h later, at 1800 h. Pituitary LH and FSH content was dramatically enhanced by 1600 h and levels remained elevated at 1800 h. The administration of pentobarbital at 1200 h, versus 1400 h or 1600 h, prevented the increase in basal serum FSH levels at 1800 h, implying that the release of hypothalamic LH releasing hormone (LHRH) is modulated by 5 alpha-DHP. In addition, changes in pituitary sensitivity to LHRH as a result of 5 alpha-DHP were measured and a significant increase in the magnitude of FSH release was observed at 1200 h and 1800 h. Although the LH response to LHRH in 5 alpha-DHP-treated rats was not different from controls, the duration of LH release was lengthened. These results suggest that 5 alpha-DHP may stimulate FSH release by a direct action at the pituitary level. Together, these observations support the theory that 5 alpha-DHP mediates the facilitative effect of progesterone on FSH secretion and further suggests an action of 5 alpha-DHP in this phenomenon at both pituitary and hypothalamic sites.

Testicular Dysfunction in Untreated Hodgkin’s Disease

Gonadal function was examined in 19 young men with Hodgkin's disease before therapy and compared with that of 11 men with other malignancies, 13 men with primary testicular failure, and 19 normal men of similar age. Total (p less than 0.01) and free (p less than 0.05) testosterone levels were decreased in Hodgkin's disease. In those with advanced (stage III + IV) and symptomatic (B), Hodgkin's disease serum testosterone levels were indistinguishable from those in primary testicular failure, yet serum levels of luteinizing hormone were normal. Moreover, the acute response of serum testosterone to exogenous human chorionic gonadotropin (HCG) was significantly greater in Hodgkin's disease than in primary testicular failure (p less than 0.03). These data and the finding that basal serum follicle-stimulating hormone levels are significantly lower than normal in Hodgkin's disease (p less than 0.05) suggest that the cause of pretreatment hypogonadism in Hodgkin's disease is not simple primary testicular failure. Total sperm count was decreased in 40 percent of men with Hodgkin's disease but in none of the men with other malignancies (p less than 0.05), suggesting specific seminiferous tubular dysfunction in Hodgkin's disease. However, motility was abnormal in 69 percent of men with Hodgkin's disease and 60 percent of those with other malignancies, suggesting that this is a nonspecific effect of cancer. Serum prolactin levels were significantly higher than normal in Hodgkin's disease (p less than 0.05) but not in other malignancies. Our findings suggests that the cause of testicular dysfunction that is present before treatment of Hodgkin's disease is complex, perhaps involving both pituitary and gonadal abnormalities.

Testicular dysfunction in untreated Hodgkin's disease

Gonadal function was examined in 19 young men with Hodgkin's disease before therapy and compared with that of 11 men with other malignancies, 13 men with primary testicular failure, and 19 normal men of similar age. Total (p < 0.01) and free (p < 0.05) testosterone levels were decreased in Hodgkin's disease. In those with advanced (stage III + IV) and symptomatic (B), Hodgkin's disease serum testosterone levels were indistinguishable from those in primary testicular failure, yet serum levels of luteinizing hormone were normal. Moreover, the acute response of serum testosterone to exogenous human chorionic gonadotropin (HCG) was significantly greater in Hodgkin's disease than in primary testicular failure (p < 0.03). These data and the finding that basal serum follicle-stimulating hormone levels are significantly lower than normal in Hodgkin's disease (p < 0.05) suggest that the cause of pretreatment hypogonadism in Hodgkin's disease is not simple primary testicular failure. Total sperm count was decreased in 40 percent of men with Hodgkin's disease but in none of the men with other malignancies (p < 0.05), suggesting specific seminiferous tubular dysfunction in Hodgkin's disease. However, motility was abnormal in 69 percent of men with Hodgkin's disease and 60 percent of those with other malignancies, suggesting that this is a nonspecific effect of cancer. Serum prolactin levels were significantly higher than normal in Hodgkin's disease (p < 0.05) but not in other malignancies. Our findings suggests that the cause of testicular dysfunction that is present before treatment of Hodgkin's disease is complex, perhaps involving both pituitary and gonadal abnormalities.

Robinow's Syndrome

We studied four patients with Robinow's syndrome. New findings included the following: (1) normal pubertal virilization with persistence of micropenis; (2) elevated basal serum follicle-stimulating hormone levels and a hyperresponse of serum luteinizing hormone to gonadorelin hydrochloride (Factrel) stimulation among postpubertal male patients, suggesting partial primary hypogonadism; (3) normal 5 alpha-reductase and androgen receptor activity in genital skin fibroblasts; and (4) normal to borderline adult height.

Serum LH and FSH responses to the repetitive administration of gonadotropin-releasing hormone in patients with idiopathic hypogonadotropic hypogonadism.

The serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the repetitive administration of synthetic gonadotropin-releasing hormone (GnRH) were studied in six male patients with idiopathic hypogonadotropic hypogonadism. Each patient received 50 mug of GnRH intravenously every four hours for 43 consecutive doses, i.e., for one week. Five of the six patients had substantially greater maximum serum LH concentrations in response to the 43rd dose than to the first dose. The mean (+/- SE) maximum serum LH concentration of all six patients following the 43rd dose (14.6 +/- 3.0 mIU/ml) was significantly (P less than 0.01) greater than that to the first dose (8.3 +/- 2.6 mIU/ml. These results suggest that the LH response of the human gonadotroph to GnRH depends on the prior exposure of the gonadotroph to GnRH. All six patients had substantially higher basal serum FSH levels prior to the 43rd dose (13.6 +/- 2.6 mIU/ml) than prior to the first dose (2.8 +/- 0.4; P less than 0.01). Four patients had increases in basal FSH level to within the normal adult male range (5-15 mIU/ml), and two had increases to above it. This uniform elevation of the serum FSH level to normal or above normal suggests that GnRH may be the primary FSH-releasing hormone as well as the primary LH-releasing hormone.

The gonadotrophin response to synthetic gonadotrophin-releasing hormone in males in relation to age, dose, and basal serum levels of testosterone, oestradiol-17beta and gonadotrophins.

ABSTRACT Three healthy male volunteers, 28–35 years old, were given an intravenous dose of 12.5, 25, 100, 200, 400, 800, and 1200μg of synthetic gonadotrophin-releasing hormone (LH/FSH-RH) in order to determine the dose-response relationship. The resulting log dose-response curve between interstitial-cell stimulating hormone (ICSH) and LH/FSH-RH was approximately linear between the 12.5 and 400 μg doses. The smallest dose that significantly (P &lt; 0.05) increased the mean serum ICSH levels was 25 μg, and 400 μg of LH/FSH-RH was the minimum dose that produced the maximum ICSH response. The increments in serum follicle-stimulating hormone (FSH) were much less than the corresponding serum ICSH increments, and the log dose-response curve was not linear. The effect of increasing age on the gonadotrophin response to LH/FSH-RH was studied in 50 male subjects, 20–89 years old, without evidence of endocrine disease. They were given 100μg of LH/FSH-RH each. A reduction in the mean response for both ICSH and FSH was observed after the age of 70, and this was most clearly seen in the group of males 80–89 years old. Therefore the interpretation of the LH/FSH-RH tests, at least in males, will require age-specific ranges of normal ICSH and FSH responses. Serum testosterone levels were determined in 48 of the male subjects investigated, and the mean serum levels remained within the same range (above 0.60 μg/100 ml) from the age of 20 to the age of 79 years. In the age group 80–89 years, the mean serum testosterone was reduced to 0.39 μg/100 ml. Serum oestradiol-17β was determined in 44 of the males, and there were no significant differences between the mean levels of the different age groups (45–55 pg/ml). There was no significant age-dependent change in basal serum ICSH and FSH levels. It is concluded that there is a parallel decrease in serum testosterone levels and in serum gonadotrophin responses to LH/FSH-RH after the age of 70. These findings would suggest that the decrease in serum testosterone levels is the result of reduced stimulation of the testicular tissue with endogenous gonadotrophins.