Basal Serum Luteinizing Hormone Levels Research Articles

P-607 Basal serum luteinizing hormone and total testosterone levels do not impact the outcomes of in-vitro fertilization in women with polycystic ovarian syndrome (PCOS)

Abstract Study question Do basal serum luteinizing hormone (LH) and total testosterone (TT) levels affect the outcomes of patients with PCOS undergoing in vitro fertilization? Summary answer LH and TT does not impact number of mature oocytes, fertilization rates, and high-quality blastocysts frozen, in PCOS with GnRH-antagonist protocol IVF with hyper-responses. What is known already The impact of basal serum LH and TT levels on IVF outcomes is debatable. Worldwide, there are many clinics that will postpone ovarian stimulation until a lower basal LH or TT is obtained in women with PCOS based on the assumption that outcomes will subsequently be more successful. However, hormones are released in a pulsatile fashion and single levels are unlikely to reflect patient status. There is a paucity of research addressing this concern. Study design, size, duration We completed a single university-centre retrospective cohort study comparing the outcomes of PCOS patients undergoing freeze-all GnRH antagonist IVF cycles divided into 50% groupings for basal serum LH and TT levels between the dates of January, 2013 and December, 2019. There were 76 women identified and confirmed on chart review to have a diagnosis of PCOS per the 2003 Rotterdam criteria. Participants/materials, setting, methods Patients were divided into the 50% with the lowest LH levels(1.0-7.0 IU/L) and highest LH(7.1-29.0 IU/L). The same was done for TT(0.30-1.50 vs. 1.6-5.6 nmol/L). These two groups were compared using chi-square test and t-test as indicated. Demographics included: serum estradiol, follicle stimulating hormone, thyroid stimulating hormone, prolactin, TT, free testosterone, gravida, parity, female age, male age, semen analysis parameters, antral follicle count, and duration of infertility. IRB approval was obtained(2020-5971). Data is X±SD. Main results and the role of chance When assessing based on LH, there were no differences in demographics(P > 0.05 in all cases) except for TT(1.4±1.0 vs. 1.9±0.9 nmol/L-p=0.02) and free-testosterone(0.6±0.5 vs. 0.9±0.5 nmol/L-p=0.03). The number of oocytes collected(26.8±7.4 vs. 27.3±9.6-p=0.82), mature oocytes(19.9± 6.8 vs. 20.2±7.8-p=0.88), and frozen high-quality blastocysts(7.0±4.4 vs. 8.2±5.1-p=0.25) were similar. The percent of MII that fertilized(75%±16 vs. 74%±19-p=0.78), the percent of 2PN that grew to blastocysts(47%±23 vs. 55%±27-p=0.18) and the percent of MII that grew to blastocyst(35%±18 vs. 40%±19-p=0.25) were similar. Among subjects who underwent embryo transfer, clinical pregnancy rates(33% vs. 45%-p=0.36) and live birth rates(22% vs 32%-p=0.39) were similar when comparing lowest vs. highest percentile, respectively. When comparing demographics by TT grouping, differences were previous pregnancies(0.9±1.2 vs. 0.3±0.7-p=0.02), serum TSH(1.66±0.96 vs. 2.43±1.90 nmol/L-p=0.04), and duration of infertility(2.3±2.0 vs 3.7±2.7years-p=0.04). The number of oocytes collected(27.5±7.5 vs. 28.3±9.7-p=0.73), MII oocytes(20.5±6.9 vs. 20.4±8.3-p=0.98), and frozen high-quality blastocysts(6.9±4.0 vs. 8.1±5.7-p=0.32) were similar. The percent of MII that fertilized(73%±19 vs. 74%±17-p=0.96), the percent of 2PN that grew into blastocysts(48%±23 vs. 53%±28-p=0.50) and the percent of MII that grew to blastocyst(34%±17 vs. 38%±19-p=0.36) were similar. Among subjects undergoing embryo transfer, clinical pregnancy rates(46% vs. 44%-p=0.90) and live birth rates(38% vs 26%-p=0.33) were similar when comparing lowest vs. highest percentile respectively. Limitations, reasons for caution Our study was limited to GnRH-antagonist cycles with freeze all embryos. Thus, findings may not be applicable to IVF cycles with fresh embryo transfer. It is a retrospective study and therefore is at risk for inherent biases. Wider implications of the findings Our findings provide reassurance that elevated basal serum LH and TT levels do not impact IVF outcomes in hyper-responding patients and therefore should not result in cycle cancellation or delay in those with PCOS undergoing GnRH-antagonist cycles with anticipated hyper-responses. Trial registration number N/A

Diagnostic evaluation of central precocious puberty in girls

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for confirming the activation of the hypothalamic-pituitary-gonadal axis in central precocious puberty (CPP). However, it is time-consuming and costly. Our aim was to search for a simpler diagnostic modality for CPP by 1) evaluating the performance of basal serum luteinizing hormone (LH), 2) constructing a practical scoring system, and 3) determining the optimal single sampling time for serum LH in the GnRH stimulation test. Data of girls aged between 3 and 9yearsat the time of the GnRH stimulation test, who attended our endocrine clinic at the MacKay Children's Hospital for signs of puberty between July 2014 and June 2019, were analyzed retrospectively. We recorded patients' age, height, weight, breast Tanner stage (BS), bone age, serum LH, and follicle-stimulating hormone (FSH). Receiver operating characteristic (ROC) curves and the Youden index were used to obtain the optimal basal serum LH level. Binary logistic regression was employed to construct a practical scoring system. Cross-sectional, cumulative frequency, and ROC curves were used to simplify the GnRH stimulation test. Overall, 381 sets of GnRH stimulation tests were performed in 313 patients. Basal serum LH≥0.2 IU/L demonstrated 70% sensitivity and 70% specificity for predicting positive GnRH stimulation test results. The practical scoring system (3×BS+3×LH+4×FSH) showed 76% sensitivity and 72% specificity. The serum LH level at 30min after intravenous gonadorelin exhibited 99% sensitivity and 100% specificity. Single sampling of serum LH at 30th minute post-injection of GnRH demonstrated a diagnostic performance equivalent to the traditional GnRH stimulation test in diagnosing CPP. Therefore, this approach could become the simplest diagnostic modality.

Relationships between Serum Luteinizing Hormone Level, Endometrial Thickness and Body Mass Index in Polycystic Ovary Syndrome Patients with and without Endometrial Hyperplasia.

The endometrial hyperplasia measured by ultrasound in polycystic ovary syndrome (PCOS) women is strongly related to pathologic endometrial thickness, but there is no consensus on the relation between serum luteinizing hormone (LH) and either of these factors: pathologic endometrial hyperplasia and body mass index (BMI). In this observational cross-sectional study, three hundred fifty infertile PCOS women were involved in this research. An endometrial biopsy was taken by using a pipelle instrument, regardless of menstrual cycle's day and all samples were reported by the same pathologist. Basal serum LH level was compared between two subgroups (hyperplasia and non-hyperplasia). The intended population was divided into three groups according to BMI and basal serum LH, later on the comparison was made in three groups. Chi-square test was applied to compare nominal variables between groups. Mann-Whitney U, and one way ANOVA tests were used to compare means on the basis of the result of normality test. The frequency of endometrial hyperplasia was 2.6%. Endometrial thickness in the patients with endometrial hyperplasia was significantly higher than that of a normal endometrium (10.78 ± 3.70 vs. 7.90 ± 2.86 respectively, P=0.020). There was no relation between endometrial hyperplasia and serum LH (P=0.600). The ANOVA test showed serum LH levels were not the same among three BMI groups (P=0.007). Post hoc test was also performed. It showed that the LH level in normal BMI group was significantly higher than those of other groups (P=0.005 and P=0.004), but there was no statistical difference between overweight and obese groups (P=0.8). We found no relationship between BMI and endometrial thickness in PCOS patients (P=0.6). Sonographic endometrial stripe thickness is predictive for endometrial hyperplasia in PCOS women. We could not find out any relationship between serum LH level and BMI with endometrial thickness in PCOS patients. However, our study confirmed a diverse relationship between serum LH level and BMI in PCOS patients.

The Utility of Basal Serum Luteinizing Hormone Levels for Screening Central Precocious Puberty in Girls

1 the pubertal response group of patients who had 5 IU/L peak LH levels in the GnRH stimulation test, and the prepubertal response group of patients who had LH levels <5 IU/L. Chronological and bone ages, height, weight, body mass index, gonadotropin response to GnRH stimulation, and basal levels of LH, fol- licle-stimulating hormone, and estradiol were studied in both groups. The relationship between basal LH and peak-stimulated LH was evaluated using Spearman's correlation. To determine the optimal cut-off val- ues of basal LH levels for differentiating between two groups, the receiver operating characteristic (ROC) curves were analyzed. Results: When the correlation between basal LH levels and peak LH after GnRH stimulation was analyzed in all subjects (N=90), basal LH levels had a statistically significant positive correlation with peak stimulated LH levels (rs=0.493, p<0.001). The cut-off level of optimal basal LH was 0.1 IU/L, according to the ROC curves. Its sensitivity was 73.3%, and its specificity was 77.8%. Conclusion: The study results showed that serum basal LH levels are useful for screening CPP in girls.

Structural diversity of the gnih/gnih receptor system in teleost: Its involvement in early development and the negative control of LH release

Gonadotropin inhibitory hormone (GnIH), via binding to GnIH receptor (GnIHR), plays a negative role on the avian and mammalian reproductive axis by inhibiting luteinizing hormone (LH) release. However, the biological significance of the GnIH/GnIHR system in other vertebrates is controversial. To demonstrate the presence of such a system in teleost, we have identified the orthologous gnih genes in zebrafish, stickleback, medaka and Takifugu. Three orthologous genes ( gnihr1, gnihr2 and gnihr3) for the gnihr were also identified in zebrafish. The zebrafish gnih precursor contains three putative LPXRFamide peptides. The three zebrafish gnihrs are typical seven transmembrane G protein-coupled receptors sharing high sequence homology with the mammalian and avian GnIHRs (GPR147). Tissue expression studies revealed that zebrafish gnih is mainly expressed in the brain, eye, testis, ovary and spleen, corroborating largely with the tissue expression patterns of the gnihrs in zebrafish. The expression patterns of gnih and its receptors at different developmental stages of zebrafish were also studied. Gnih expression first appeared in the prim-5 stage, and thereafter maintained at a relatively constant level. The three gnihrs could be detected at all embryonic stages of zebrafish and also during early development after hatching. The biological action of the teleost gnih on LH release was further investigated in goldfish in vivo. Intraperitoneal administration of the mature zebrafish gnih peptide (LPXRFa peptide-3) could significantly reduce the basal serum LH level in goldfish. These results provided the first evidence that gnih plays an important role in the negative regulation of LH release in teleost.

Effect of chronic l-DOPA administration on serum luteinizing hormone levels in male rats

We examined whether the repeated oral administration with a high dose of l-3-(3,4-dihydroxyphenyl)-alanine ( l-DOPA) in 0.5% carboxymethyl cellulose increases serum luteinizing hormone (LH) levels in male rats. Serum LH levels were increased 4 h after a single administration of 1000 mg/kg l-DOPA to male rats, and returned to control levels within 8 h after administration. Four hours after a single administration, serum LH levels were significantly increased by l-DOPA at 1000 mg/kg, but not at 20, 100 or 200 mg/kg. Decreases in body weight and relative weight of the prostate were observed after 7 and 14 days of administration of 1000 mg/kg per day l-DOPA, but no changes were observed in weight of the testis, epididymis or seminal vesicle. The administration of l-DOPA at 500 or 1000 mg/kg per day for 7 or 14 days resulted in increased basal serum LH levels and decreased basal serum prolactin levels 24 h after the last administration. Serum testosterone levels tended to be higher in treated than in control rats. The levels of two metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in rats treated with 500 mg/kg per day tended to be slightly higher than those in control rats after 7 days of administration. Levels of DA, DOPAC and HVA were significantly increased after 7 and 14 days of administration of 1000 mg/kg per day and after 14 days of administration of 500 mg/kg per day. The level of norepinephrine, but not its metabolite 3-methoxy-4-hydroxyphenylglycol, was significantly increased after only 7 days of administration of 1000 mg/kg per day. No significant changes were observed in levels of 5-hydroxytryptamine or its metabolite 5-hydroxyindole-3-acetic acid with administration of 500 or 1000 mg/kg per day. These findings suggest that a prolonged treatment with a high dose of l-DOPA in male rats induces release of LH from the pituitary, resulting in sustained elevation of LH levels in peripheral circulation.

Hypothalamic luteinizing hormone-releasing hormone content and serum luteinizing hormone levels in male rats during wallerian degeneration of sympathetic nerve terminals after superior cervical ganglionectomy

The main hypothesis of this study was that sympathetic neurons located at the superior cervical ganglia (SCG) control luteinizing hormone (LH) releasing mechanisms by acting at a hypothalamic site. To test this, medial basal hypothalamus (MBH) luteinizing hormone-releasing hormone (LHRH) content and serum LH levels were measured in male rats subjected to superior cervical ganglionectomy (SCGx) or sham-operation 14 or 38 h earlier, at the time of degeneration of nerve endings post-SCGx. Significantly augmented MBH LHRH levels and decreased circulating LH were found in SCGx rats. In animals subjected to SCGx 14 h earlier and receiving a single injection of the alpha 1-adrenergic blocker prazosin, the beta-adrenergic blocker propranolol or a mixture of both drugs 45 min before sacrifice, only the injection of prazosin prevented the decrease of plasma LH levels. Neither treatment prevented the increase in MBH LHRH content. When prazosin was given every hour starting from the 10th to the 13th h after surgery, it was effective to prevent both the increase of MBH LHRH content and the decrease of serum LH found during sympathetic nerve degeneration. Similar repetitive injections of propranolol resulted in the greatest depression of serum LH, and in the greatest increase of MBH LHRH observed. Serum LH response to LHRH injection was similar in SCGx and sham-operated rats. The data indicate that SCG neurons exert, through inhibitory alpha 1-, and weaker, stimulatory beta-adrenoceptors, a significant influence on LHRH release at a supra-hypophysial site.

Influences of luteinizing hormone releasing hormone, hypophysectomy and orchidectomy on the differentiation of luteinizing hormone and follicle-stimulating hormone cells and in an ectopic pituitary in the hamster.

In these experiments we examined the effects of luteinizing hormone releasing hormone (LHRH) and gonadal and pituitary hormones on the appearance of luteinizing hormone (LH) and follicle-stimulating hormone (FSI-I) cells in ectopic pituitaries in the hamster. As a reference, we first determined the sequence of appearance of these hormones in perinatal animals using immunohistochemical (IHC) and radioimmunoassay (RIA) procedures. Neither hormone could be detected in pituitaries at 13 days of gestation by either technique. Both hormones could be detected by IHC at 15 days of gestation using anti-rat LH S4, anti-rat LH�3, anti-rat FSH S-7, and anti-rat FSI-Ia antisera. Il-IC and RIA revealed an increase in gonadotroph population and gonadotrophin content, respectively, between 5 and 12 days of postnatal life. By Day 8 a sex difference emerged with RIA so that by Day 12 both pituitary LH and FSH content were higher in females. In serum, only FSH was higher in females. To study the determinants of gonadotroph differentiation, fetal (Days 13-15 of gestation) or postnatal pituitaries (<3 days) were transplanted to a site remote from the hypothalamus (beneath the renal capsule) of hosts whose endocrine state could be manipulated easily (adult male hamsters). The hosts were intact, hypophysectomized, orchidectomized, or hypophysectomizedorchidectomized hamsters. Some hosts were also treated with LHRH (dosages of 5, 30 or 50 Mg/day for 4, 12 or 19 days). In grafts of any hosts not treated with LHRH, the number of detectable FSH cells was always much less than the number of LH cells. LHRH treatment of any host increased the number of LH and FSH cells detected. After 19 days of treatment, the numbers of LH and FSH cells identified were approximately equal. Both gonadotrophins often were found in the same cell. In nonhypophysectomized hosts, with or without testes, LHRH often produced a significant depression of serum LH when measured 16 h after the last injection. Although LHRH did not alter basal serum LH levels in hypophysectomized hosts 16 h after the last injection, it did elevate serum LH in similar hosts forat least3 h after the injection. In nonhypophysectomized hosts with testes, LHRH significantly elevated serum FSH levels. However, LHRFI did not alter serum FSH in orchidectomized hosts. A tendency for LHRH to increase basal serum FSH levels in hypophysectomized or hypophysectomized-orchidectomized hosts existed. These experiments revealed that when pituitaries were removed from perinatal hamsters and placed in an ectopic site the accumulation of intracellular LH was greater than FSH. This result was not affected by hypophysectomy and/or orchidectomy of the hosts. The resemblance of the development of gonadotrophs in the in situ pituitary with that in ectopic pituitaries in hosts treated with LHRH suggests that LHRH may be a major determinant of normal gonadotroph differentiation.

Dopamine: effects on prolactin and luteinizing hormone secretion in ovariectomized rhesus macaques after transection of the pituitary stalk.

Luteinizing hormone (LH) and prolactin (PRL) levels were compared in the serum of ovariectomized rhesus macaques (Macaca mulatta) with pituitary-intact (PI) and surgically transected pituitary stalks (SS). After stalk sectioning, LH levels declined and PRL levels rose dramatically. Chronic infusion of intermittent pulses of gonadotropin-releasing hormone (GnRH; 1 microgram/min for 6 of every 60 min) into SS females reinitiated LH secretion within a few days despite increased PRL secretion. Continuous infusion of dopamine (10 micrograms/min/kg of body weight) for 9 days suppressed PRL levels in GnRH-infused SS females to near normal without alteration in basal serum LH levels or pulsatile LH release. A comparable dopamine regimen also failed to modify serum LH patterns in PI monkeys. Immediately after cessation of dopamine, serum PRL levels rose sharply in both PI and SS animals. Injection of estradiol benzoate (42 micrograms/kg of body weight) into SS monkeys receiving GnRH infusions resulted initially in LH suppression and then in LH release. However, the magnitude of LH release was less and the latency to its onset was longer in SS animals given estrogen than in PI controls with similar serum estrogen concentrations. It is unclear whether the atypical pattern of the estrogen-induced LH release in SS monkeys was due to hyperprolactinemia or other deficiencies in this GnRH-infused model. However, these data indicate that the response of gonadotropes to GnRH stimulation was not altered by a direct action of either PRL or dopamine on the pituitary gland. Conversely, dopamine directly suppressed the lactotrope, which became hypersecretory immediately upon dopamine withdrawal. We have concluded that estrogen-induced inhibition and subsequent augmentation of LH release represents a direct action at a pituitary locus, although effects at additional, nonpituitary loci are not precluded.

11 DISPARITY BETWEEN BIOACTIVE AND IMMNOACTIVE LUTEINIZING HORMONE IN GIRLS WITH GONADAL DYSGENESIS: EFFECT OF ESTROGEN TREATMENT

We have studied the ratio of bioactive to immunoactive (B/I) luteinizing hormone (LH) in eight girls with gonadal dysgenesis before and after estrogen replacement therapy with low doses of oral ethinyl estradiol. The estrogen suppression of bioactive LH, as measured by a rat interstitial cell testosterone assay (RICT), was more profound than the suppression of radioimmuno-assayable (RIA) LH in five girls who had elevated basal serum LH levels: The B/I before therapy was significantly higher (p<0.005) at 2.78±0.12 (n=6) than after three months of 10 μg of ethinyl estradiol (1.44±0.11, n=5), and after three subsequent months of 20 μg of ethinyl estradiol (0.60±0.08, n=3). In two younger patients without elevated basal RIA LH, however, the B/I was low. Estradiol 17-β in concentrations of 0.1, 5 and 10 ng/ml had no effect on testosterone production in the RICT assay.

Luteinizing hormone secretion in patients presenting with post-oral contraceptive amenorrhoea: evidence for a hypothalamic feedback abnormality.

Twenty-four patients who presented with amenorrhoea after discontinuing oral contraceptives were studied. In fourteen patients underlying conditions were present which could account for the amenorrhoea. Two patients were pregnant, two had premature ovarian failure and four polycystic ovarian disease. Pituitary tumours were present in three patients, and in another three radiological abnormalities of the pituitary fossa suggested the presence of an intrasellar tumour. Basal serum luteinizing hormone levels reliably differentiated ovarian from hypothalamic or pituitary lesions. Varied patterns of serum LH response to clomiphene were present in the patients with post-oral contraceptive amenorrhoea or pituitary lesions. Most patients showed normal hormone response patterns, with a secondary LH peak, but in others a partial response only was seen. In the latter group, who responded normally to exogenous gonadotrophin releasing hormone, no secondary LH peak occurred despite normal oestradiol responses. This suggests an abnormality of the positive feedback system for oestrogens. Subsequent stimulation with clomiphene produced normal LH responses in these patients showing that the abnormality was reversible. These findings are consistent with the hypothesis that post-oral contraceptive amenorrhoea is the result of continuing suppression of normal hypothalamic pituitary feedback systems after the sex steroids have been stopped. The different patterns of hormone response to clomiphene suggest varying degrees of feedback abnormality, and in some patients the positive feedback mechanism only is impaired.