OBJECTIVESTo measure continuously the urine beta-FSH excretion in the patients with male hypogonadism, and to evaluate the significance of urine beta-FSH when used in the clinical practice and pathophysiological study on male hypogonadism.

METHODSFour health male volunteers (aged 19, 22, 27 and 33 years), four patients with the hypogonadotropic hypogonadism (aged 17, 17, 19 and 24 years) and five patients with idiopathy hypogonadism (hypergonadotropic, aged 16, 16, 17, 20 and 22 years) were asked to collect their morning-first urine samples for 30 to 32 days. One normal men collected his urine samples for 63 days. The urine beta-FSH was assayed with the method of EIA, then corrected by creatinine (Cr) concentration.

RESULTSThe urine beta-FSH level of normal men was (1.16 +/- 0.20) micrograms/mg Cr, with the peak variation in their curves, peak level at 2.76 micrograms/mg Cr. The levels of urine beta-FSH of 4 patients with the hypogonadotropic hypogonadism were lower significantly than those of normal men [(0.58 +/- 0.31) (0.93 +/- 0.47) (0.47 +/- 0.33) and (0.60 +/- 0.40) micrograms/mg Cr], without fluctuation in their curves. beta-FSH levels of 5 patients with idiopathy hypogonadism were higher significantly [(3.02 +/- 0.93), (4.36 +/- 1.12), (4.79 +/- 0.78), (4.64 +/- 1.42) and (3.88 +/- 1.42) micrograms/mg Cr], with irregular fluctuation, the highest peak level at 6.83 micrograms/mg Cr. The second sexual characteristics of hypogonadal patients were poor and serum testosterone levels low.

CONCLUSIONSThe urine beta-FSH level raised with irregular fluctuation in patients with idiopathy hypogonadism, while lowed without any fluctuation in patients with the hypogonadism. These findings suggested that the urine beta-FSH excretion was useful for the clinically classified diagnoses and pathophysiological study on male hypogonadism, and for observing the treatment reaction of androgen replacement.

Adolescent ; Adult ; Follicle Stimulating Hormone, beta Subunit ; urine ; Humans ; Hypogonadism ; metabolism ; urine ; Luteinizing Hormone ; urine ; Male ; Testosterone ; urine

ObjectiveTo study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men.

METHODSThis case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software.

RESULTSThere were statistically significant differences between the control and infertility groups in the semen volume (［3.51 ± 1.36］ vs ［3.74 ± 1.71］ ml, P <0.05), sperm concentration (［79.21 ± 61.60］ vs ［27.37 ± 30.80］ ×10⁶/ml, P <0.01), percentage of progressively motile sperm (［39.40 ± 9.64］ % vs ［11.90 ± 14.72］ %, P <0.01), and levels of serum luteinizing hormone (LH) (［3.29 ± 1.39］ vs ［6.25 ± 4.83］ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (［4.56 ± 2.31］ vs ［15.64 ± 17.03］ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility.

CONCLUSIONSThe rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.

Adult ; Azoospermia ; genetics ; Case-Control Studies ; China ; Follicle Stimulating Hormone ; Genotype ; Haplotypes ; Humans ; Infertility, Male ; genetics ; Logistic Models ; Luteinizing Hormone ; Luteinizing Hormone, beta Subunit ; genetics ; Male ; Oligospermia ; genetics ; Polymorphism, Single Nucleotide ; Sperm Count

Serum levels of LH, FSH and prolactin and plasma levels of estradiol and progesterone were measured by radioimmunoassay from 8 healthy volunteers on no medication for at least 3 months prior to study and with histories of regular menstrual cycle. The following criteria were used to define a normal menstrual cycle:1) mid-cycle LH surge, 2) luteal phase duration between 12 and 16 days, 3) plasma progesterone levels above 5 ng/m1 5-10 days after LH surge. Six of eight cycles studied were considered normal. Serum levels of LH from 6 women were fair1y constant through the cycle, except at midcycle, when a surge occurred. The rapid increase of LH secretion was during the late follicular phase with a mean peak value of 147.5 mIU/ml. Concentration of FSH started to rise after the onset of menses and decreased slight1y during the late follicular phase. FSH rose sharply at midcycle with a mean peak value reaching 36.8 mIU/ml. Following the midcycle FSH and LH surge, FSH and LH decreased sharply and remained at lower concentration during the luteal phase than during the follicular phase. Serum prolactin concentrations fluctuated throughout the menstrual cycle. There was no peak value of prolactin concomitant to the LH peak. Plasma estradiol gradually increased during the follicular phase reaching a maximum of 354.3 pg/ml prior the midcycle LH surge. Following its peak, the level of estradiol dropped sharply and started to increase from the 3rd day after LH peak, rising to 235.9 pg/ml during the midluteal peak. Plasma progesterone levels remained consistently low during the follicular phase and started to rise after the midcycle surge of LH. This rise persisted from day 5 to day 9 after the LH surge, showing a mean value of 26.1 ng/m1. Afterward, a sharp decline occurred resulting in menstruation. Two cycles studied were considered abnormal. Both cycles showed a "short luteal phase".
Estradiol/blood ; Female ; Follicle Stimulating Hormone/blood ; Gonadotropins, Pituitary/blood* ; Human ; Korea ; Luteinizing Hormone/blood ; Menstruation* ; Progesterone/blood ; Prolactin/blood ; Sex Hormones/blood*

BACKGROUNDDelayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.

METHODSA study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed.

RESULTSThe ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.

CONCLUSIONSOur data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

Adolescent ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; pharmacology ; Gonadotropins ; deficiency ; Humans ; Hypogonadism ; blood ; diagnosis ; Hypothalamus ; drug effects ; Luteinizing Hormone ; blood ; Male ; Pituitary Gland ; drug effects ; Puberty, Delayed ; blood ; diagnosis ; Sensitivity and Specificity

BACKGROUND: Follicle-stimulating hormone (FSH), a gonadotropin secreted by the pituitary gland, is a representative secondary sex hormone and an important indicator of reproductive function. The effects of heavy metals such as lead, cadmium, and mercury on humans have been studied, but reports on their effects on sex hormone levels are lacking. Therefore, we investigated the relationship between heavy metal exposure and FSH levels in Korean men and postmenopausal women. METHODS: A total of 4,689 adults (2,763 men and 1,926 postmenopausal women aged 50 years or over) who participated in the Second Korean National Environmental Health Survey (2012–2014) were included. We compared differences in serum FSH levels by demographic characteristics using the t-test and analysis of variance. Multiple linear regression analysis was used to determine the relationship between the blood levels of lead and mercury and the urine cadmium level, and serum FSH levels. RESULTS: On multiple linear regression analysis, lead exposure was positively associated with serum FSH concentrations in postmenopausal women (β = 2.929, p = 0.019). However, we found no significant association between serum FSH concentration and blood lead and mercury levels, or urine cadmium level, in men. CONCLUSIONS: This study suggests that lead exposure can affect the FSH level in postmenopausal women. Further studies are needed to evaluate the effects of low-dose long-term exposure to heavy metals on sex hormones.
Adult ; Cadmium ; Environmental Health ; Female ; Follicle Stimulating Hormone ; Gonadal Steroid Hormones ; Gonadotropins ; Humans ; Linear Models ; Male ; Metals, Heavy ; Pituitary Gland

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l^-1 or LH ≥2 IU l^-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l^-1 to 7.5 ± 4.4 IU l^-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l^-1 to 8.8 ± 5.3 IU l^-1. A Cox regression analysis showed that basal testosterone level (β = 0.252, P = 0.029) and triptorelin-stimulated FSH_60min(β = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl^-1 versus 248 ± 158 ng dl^-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH_60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.
Adult ; Cohort Studies ; Follicle Stimulating Hormone/blood* ; Gonadotropin-Releasing Hormone/therapeutic use* ; Gonadotropins/blood* ; History, 16th Century ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/blood* ; Male ; Pituitary Gland/pathology* ; Predictive Value of Tests ; Retrospective Studies ; Sperm Count ; Testis/pathology* ; Testosterone/blood* ; Treatment Outcome ; Triptorelin Pamoate/therapeutic use* ; Young Adult

Follicle stmulating hormone ( FSH ) consist of alpha and beta subunits, which are encoded by se-parate genes. Pituitary release of FSH appears to be regulated by the hypothalamic GnRH and the gonadal steroid hormones. In addition, inhibin and follistatin produced by the gonad have been known to inhibit FSH secretion selectively. However, little is known about their regulation of the biosynthesis of FSH subunits at transcriptional and posttranscriptional levels. In the pre-sent study, we studied the time course of changes in alpha and FSH beta subunit mRNA concentrati-ons after castration and the effects of ovarian steroids of changes in alpha and FSH beta subunit mRNA concentrations after castration and the effects of ovarian steroids on alpha and FSH beta subunit mRNA in ovariectomized rats in order to determine Whether FSH subunit synthesis is modulated at the pretranslational levels, and whether synthesis and secretion are differently regulated. Results are as follows : 1. The time course of the rise in the steady state alpha subunit and FSH beta subunit mRNA levels were observed after ovariectomy, which paralleled the increases in serum and pituitary FSH concentrations. The time course experiments revealed differences in the patterns of alpha and FSH beta subunit mRNA responses, the rise in FSH beta subunit mRNA levels being more pro- minent than the rise in alpha subunit mRNA. 2. FSH beta mRNA levels were negatively regulated by the single injection of progesterone but not by estradiol, suggesting that FSH beta subunit mRNA seemed to be more sensitive to ne-gative feedback by progesterone than estradiol. Similar results were obtained by the continuous treatment of ovarian steroids for 1~4 days, but inhibition was more prominent with continuous treatment. It is, therefore, concluded that estradiol and progesterone inhibit the synthesis of FSH at the pretranslational level by modulating the steady state levels of alpha and FSH beta subunit mRNA, progesterone effect being more promiment than that of estradiol and alpha and FSH beta subunit are regulated in a different manner.
Animals ; Castration ; Estradiol ; Female ; Follicle Stimulating Hormone* ; Follicle Stimulating Hormone, beta Subunit ; Follistatin ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Gonads ; Inhibins ; Ovariectomy* ; Progesterone ; Rats* ; RNA, Messenger* ; Steroids

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.
Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, beta Subunit ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Injections, Subcutaneous ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Recombinant Proteins ; Syringes

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.
Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Follicle Stimulating Hormone, beta Subunit ; Follicle Stimulating Hormone, Human ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Injections, Subcutaneous ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Recombinant Proteins ; Syringes

OBJECTIVETo investigate the relationship of plasma ghrelin and adenohypophyseal hormone levels in female precocious puberty.

METHODSA total of 84 patients aged from 6 to 9 years were enrolled in this study. They were divided into idiopathic central precocious puberty (ICPP) and premature thelarche(PT)groups according to their secondary sexual characteristics, bone age, volumes of uterus and ovary, and results of GnRH test. Plasma ghrelin levels were measured by radioimmunoassay. ACTH, TSH, PRL, GH, LH and FSH were measured by chemoluminescence technique.

RESULTSGhrelin levels in ICPP group were Log (2.42+/-0.26) ng/L, which were significantly lower than those in PT group and controls [Log (2.62+/-0.21) ng/L and Log (2.58+/-0.44) ng/L, respectively, P<0.05]. However there was no significant difference between PT group and controls(P>0.05). Ghrelin levels of ICPP girls with Tanner III were Log (2.31+/-0.24) ng/L, significantly lower than those of ICPP girls with Tanner II [Log (2.53+/-0.24) ng/L, P<0.05]. By bivariate correlation analysis, ghrelin levels in precocious puberty girls were negatively correlated with ACTH, PRL and LH15, LH30 and LH60 in GnRH test(r=-0.248, -0.235, -0.445, 0.405, 0.398, respectively, P<0.05). No significant correlation was found between ghrelin and GH, LH0(-2), FSH0(-2), and FSH15, FSH30 and FSH60 in GnRH test.

CONCLUSIONICPP girls have lower plasma ghrelin levels, which are decreased with the development of Tanner stage. The plasma ghrelin levels are negatively correlated with ACTH, PRL and LH.

Adrenocorticotropic Hormone ; blood ; Child ; Female ; Ghrelin ; blood ; Gonadotropins, Pituitary ; blood ; Humans ; Luteinizing Hormone ; blood ; Puberty, Precocious ; blood