Adverse effects of luteinizing hormone on fertility: fact or fantasy

High tonic serum concentrations of luteinizing hormone (LH) in the follicular phase, frequently witnessed in polycystic ovary syndrome, have been associated with decreased reproductive function. Impaired rates of fertilization, conception and miscarriage are obtained when LH levels are high before oocytes are collected, during ovulation induction or in women with regular cycles. Conversely, treatment that decreases LH concentrations, such as gonadotrophin-releasing hormone analogue or laparoscopic ovarian puncture, eases induction of ovulation and pregnancy and improves miscarriage rates. Tonic hypersecretion of LH appears to induce premature oocyte maturation, causing the problems with fertilization and miscarriage.     

Sperm counts and reproductive hormones in male marathoners and lean controls

In women, chronic and intense endurance exercise is frequently associated with menstrual cycle alterations. In men, the effects of similar amounts of exercise are less well-studied. We tested the hypothesis that endurance exercise in men is also associated with alterations in reproductive function. We studied 12 marathon runners and 12 age-matched, lean controls; serum and semen samples were collected every 2 weeks for 12 weeks. Sperm counts, sperm morphologies, and mean levels of testosterone (T), free T, sex hormone binding globulin, cortisol, follicle-stimulating hormone, and biologically active luteinizing hormone (LH) were similar in the two groups. Mean levels of immunologically active LH were somewhat higher in the marathoners. We conclude that this level of strenuous, long-term endurance exercise does not have major adverse effects on reproductive function in men.     

Effect of human corticotropin-releasing hormone on gonadotropin secretion in cycling and postmenopausal women.

OBJECTIVE: To test the hypothesis that corticotropin-releasing hormone (CRH) is linked to stress-associated reproductive dysfunction in the human by determining if the administration of human corticotropin-releasing hormone (hCRH) results in an inhibition of gonadotropin secretion. DESIGN: Twenty-four-hour prospective study with frequent (every 10 minutes) blood sampling. SETTING: University Clinical Research Center. INTERVENTIONS: Sequential 8-hour infusions of normal saline, hCRH (1 to 5 micrograms/kg per hour), and hCRH plus naloxone (2 mg/h). SUBJECTS: Four normal cycling women and four postmenopausal women. MAIN OUTCOME MEASURES: Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and adrenal and ovarian steroids. RESULTS: In response to hCRH, a prompt and sustained rise in cortisol (F) was noted in both normal cycling women and postmenopausal women. No inhibition of LH or FSH was noted during either the hCRH or hCRH plus naloxone infusion in either group of women. Unexpectedly, elevations in the mean LH peak amplitude and the transverse mean LH concentration were noted in the postmenopausal women during the infusion of hCRH as compared with saline. The infusion of hCRH had no apparent effect on concentrations of PRL, FSH, and gonadal and adrenal steroids (except for F). CONCLUSIONS: Under these conditions, intravenously administered hCRH has no inhibitory effect on gonadotropin secretion in either premenopausal or postmenopausal women. The mechanism by which stress exerts its deleterious effect on reproductive function in the human remains unknown.     

Impact of ovarian stimulation on corpus luteum function and embryonic implantation

The luteal phase has been found to be defective in virtually all the stimulation protocols used in in-vitro fertilization (IVF), indicating that common mechanisms might be involved despite the use of different drugs. A normal luteal phase is characterised by a normal hormonal environment, normal progesterone secretion by the corpus luteum and adequate endometrial secretory transformation. Luteinizing hormone supports the corpus luteum and luteal luteinizing hormone (LH) levels have been found to be reduced in human menopausal gonadotrophin (HMG), gonadotrophin-releasing hormone (GnRH)-agonist/HMG and GnRH-antagonist/HMG protocols, probably leading to an insufficient corpus luteum function. Supraphysiological steroid serum concentrations routinely observed in stimulated cycles may adversely affect LH secretion and induce a luteal-phase defect. In turn, these high steroid serum concentrations may advance early luteal-phase endometrial development leading to embryo-endometrial asynchrony and decreased pregnancy rates in IVF cycles.     

Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria.

Despite consistent evidence that premenstrual dysphoria (PMD) is not characterized by abnormalities in basal ovarian hormone secretion, the possibility remains that PMD is associated with an abnormality in the regulation of the hypothalamic-pituitary-ovarian (HPO) axis. We studied HPO axis regulation in 11 women with prospectively confirmed PMD and 20 asymptomatic controls, during both the follicular and luteal phases of the menstrual cycle. Plasma levels of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), were obtained before and after stimulation with gonadotropin-releasing hormone (GnRH) (100 microg intravenously). Potential diagnostic- and menstrual cycle phase-related diferences in basal and plasma hormone levels were analyzed by repeated-measures analysis of variance. No significant differences were observed between women with PMD and controls in either basal or stimulated levels of FSH and LH. Stimulated FSH was significantly increased and stimulated LH was significantly decreased during the follicular compared with the luteal phase in both women with PMD and controls. These data are consistent with prior findings of normal basal reproductive hormone levels in women with PMD. Our data suggest the absence in women with PMD of an abnormality of dynamic ovarian function as measured by GnRH stimulation.     

Abnormal pattern of luteinizing hormone pulsatility in women with epilepsy

Dysfunction of the hypothalamic-pituitary-ovarian axis in epileptic females has been suggested in the latest years. To further elucidate this issue, we assessed reproductive endocrine function in 10 normally cycling, drug-free epileptic women and in 5 normal controls, evaluating the basal hormonal profile and luteinizing hormone (LH) pulsatility in the midfollicular phase. Luteinizing hormone pulse frequency was significantly higher in epileptic women with a consequent reduction of the LH interpulse interval. We suggest that epilepsy may interfere with the functional activity of the gonadotropin-releasing hormone pulse generator. The pathogenetic mechanisms for this phenomenon may be the spreading of paroxysmal activity within the hypothalamic areas or, alternatively, a neurotransmitter dysfunction giving rise both to the seizure disorder and to the abnormal LH pulsatile pattern.     

Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease

OBJECTIVE: To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). DESIGN: Comparative study of endocrinologic parameters in subjects with PCOD. SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). RESULTS: The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = -0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = -0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = -0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). CONCLUSIONS: These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup.     

Plasma oxytocin concentrations during the menstrual cycle

Concentrations of oxytocin have been measured in plasma samples obtained daily from 6 women throughout complete menstrual cycles. Measurements of menstrual blood loss and plasma levels of luteinizing hormone (LH), progesterone and 17β-oestradiol suggested that normal ovulatory cycles were studied. A significant elevation in the circulating concentration of oxytocin was found in association with peak levels of LH. It is suggested that oxytocin may have a role in the process of ovulation in the human female.     

Sex hormones in women on hemodialysis

The pituitary-ovarian axis was studied in 12 women with a creatinine clearance of less than 5 ml/min per 17 m2, established on regular hemodialysis for at least 12 months. Follicle stimulating hormone (FSH) serum levels were found to be slightly lower than normal, luteinizing hormone (LH) plasma concentration generally elevated, while progesterone and estradiol values were extremely low. The major reproductive consequence of chronic renal failure in women on hemodialysis is a severe impairment in ovulatory function.     

Immunoradiometric assays of total renin and gonadotropins in serum during the menstrual cycle

The contribution of the ovary to the circulating total renin pool is linked to its secretory activity in relation with its reproductive function. In a longitudinal study of 13 normal women, total renin levels measured in serum by an immunoradiometric assay were lower in the midfollicular phase (180 +/- 59 pg/ml) than in the midluteal phase (291 +/- 100 pg/ml). Peak levels were encountered 1 day after the luteinizing hormone (LH) surge (375 +/- 97 pg/ml). Rapid circhoral fluctuations were observed in all periods of the cycle, unrelated to the LH pulses. In case of ovarian function inhibition (induced by gonadotropin-releasing hormone agonists), total renin levels were lower than in the midfollicular phase (126 +/- 56 pg/ml). Low levels also were encountered in the prepubertal period (153 +/- 89 pg/ml). Very high levels (17,600 +/- 11,400 pg/ml) were found in follicular fluids from stimulated cycles. These results show that circulating total renin levels follow a complex pattern in which LH, but possibly also follicle-stimulating hormone and gonadal steroid hormones (estradiol and progesterone), may play a role.     

Role of sex-hormone-binding globulin in hormonal changes and amenorrhoea in thyrotoxic women.

Plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), oestrogen, testosterone and sex-hormone-binding globulin (SHBG) were determined in 15 thyrotoxic women in the reproductive age before and after treatment with carbimazole. The levels of these hormones and SHBG were compared with those of 12 euthyroid healthy female volunteers of comparable age and parity. Plasma gonadotrophins (LH and FSH), oestrogen, testosterone and SHBG were all markedly elevated in thyrotoxic subjects but became normal when the euthyroid state and normal menstruation were restored after treatment. From the results a hypothesis is suggested that related the hormonal disturbance primarily to a thyroid hormone-induced rise in SHBG levels.     

Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats.

The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.     

不同病因无精子症的生殖激素水平

目的 :探讨不同病因无精子症患者生殖激素水平及病变部位和睾丸生精功能的关系。方法 :采用 RIA法检测 6 5 1例患者血清中的生殖激素 FSH、LH、T、PRL值。结果 :FSH值升高者 ,病变在睾丸 ,且生精功能受损 ;而在正常值上限 2倍以上 ,则生精功能丧失。病变不在睾丸和特发性无精子症者 ,FSH值水平正常或低下 ,LH、T、PRL值不一 ,部分患者生精障碍可随疾病的治愈而恢复。结论 :生殖激素水平可表示无精子症的不同病因 ,FSH值的升高是睾丸生精功能损伤的指标     

The most frequent hormone dysfunctions in juvenile bleeding

The main goal of this study was to investigate the precise hormone dysfunction that leads to dysfunctional uterine bleeding (DUB) in adolescent girls so that, with the appropriate therapy, the occurrence of organic dysfunctions of their reproductive function can be prevented. This study included 70 adolescents with DUB aged 14.70 +/- 1.70 and 30 healthy adolescents aged 13.7 +/- 1.83. Hormone examinations indicated the presence of three typical endocrinological findings of the adolescents with DUB: the first group with FSH values within the normal range, but low LH values, the lower value of estradiol and absence of hyperandrogenism; the second group with higher LH values and normal FSH values but one third with hyperandrogenism; and the third group with normal FSH and LH values, but with hyperinsulinemia and hyperandrogenism. Comparing the hormone values obtained in the control group and the group with DUB, we have concluded that hyperandrogenism, hyperinsulinemia, lower values of progesterone, and dysfunctions in secretion of gonadotropin are statistically important factors for the origin of juvenile bleeding.     

A pharmacokinetic and endocrine comparison of recombinant follicle-stimulating hormone and human menopausal gonadotrophin in polycystic ovary syndrome

Elevated LH concentrations are frequently encountered in patients with polycystic ovary syndrome (PCOS) and increased LH (either endogenous or superimposed through the use of HMG) may have detrimental effects on reproductive function. In spite of this, FSH-only products and HMG have been used indiscriminately for ovulation induction - on the basis that the administration of HMG to patients with PCOS, who are not receiving GnRH agonists, does not result in significant increases in serum LH concentrations as judged by daily single blood samples. However, both endogenous and exogenous LH have a relatively short terminal half-life and studies have reported normal serum LH, but abnormal urinary LH and emphasized that early morning urinary measurements are more informative than those in serum because they reflect nocturnal LH secretion. Therefore, the present study was undertaken to perform a pharmacokinetic and endocrine comparison of recombinant human FSH and HMG in PCOS patients including LH measurements in the urine. Five PCOS patients receiving s.c. recombinant human FSH (rhFSH) and five PCOS patients receiving i.m. HMG for ovulation induction according to a chronic low-dose step-up regimen underwent blood and urine sampling at the following study points: Point 0 was the day of HCG injection; Points 1 to 5 corresponded to days HCG -1 to -2; -3 to -4; -5 to -6; -7 to -8; and -9 to -10; respectively. Serum hormone measurements included oestradiol, FSH, LH, progesterone, inhibin A, androstenedione, testosterone, and free testosterone index. FSH and LH were also measured daily in 8-h urine samples reflecting overnight renal urine secretion. Hormone concentrations calculated as the area under the curve showed that both FSH and LH concentrations in urine were significantly higher in HMG group than in group rhFSH. It is concluded that both LH and FSH concentrations significantly accumulate in the urine of PCOS patients receiving HMG for ovulation induction in a chronic low-dose protocol as compared with rhFSH treatment.     

Evaluation of semen and pituitary gonadotropin function in men with untreated Hodgkin's disease

The reproductive capacities of 35 patients with Hodgkin's disease were assessed before treatment by semen evaluation and determination of basal hypothalamic-hypophyseal function and after stimulation with gonadotropin-releasing hormone (GnRH). Sixty-five percent of the patients had asthenozoospermia, 46% had teratozoospermia, and 28% had oligozoospermia. Normal semen was more frequently seen in asymptomatic patients (7 of 18) than in symptomatic patients (2 of 15). All the patients had normal basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and significantly low testosterone (T) levels (P less than 0.01). The FSH response to 100 micrograms of GnRH was normal, but the LH responses were all significantly low, both as delta % (28.4% +/- 18.7% versus 52.4% +/- 25.3%, P less than 0.005) and as peak values (36.7 +/- 20.7 mIU/ml versus 59.4 +/- 26.4 mIU/ml, P less than 0.01). It is believed that abnormal semen is a specific symptom of Hodgkin's disease, secondary to functional insufficiency of the hypothalamic-hypophyseal axis, with a relative decrease in T production.     

Comparative study of serum luteinizing hormone levels in human subjects as measured by radioimmunoassay and radioreceptorassay

A rapid, precise, sensitive, and specific radioreceptorassay (RRA) for serum luteinizing hormone (LH), using a 15,000 X g pellet from bovine corpora lutea, was developed. A comparative study of the serum LH levels in human subjects as measured by this RRA and by radioimmunoassay (RIA) using the same standard preparation was then conducted. The serum LH profile throughout the entire menstrual cycle and the pituitary responsiveness to LH-releasing hormone (LH-RH) stimulation during the two phases of the cycle were studied in two normal women. In addition, LH levels in two normal postpubertal men were measured in blood samples obtained before and after LH-RH administration. Similar, although not identical, LH profiles were found in all cases by both hormone assay methods. Higher RRA-assayable LH values were obtained throughout the menstrual cycle as compared with those obtained by RIA. A significant LH-RH pituitary response in terms of LH in both RRA and RIA during the luteal phase was observed as compared with that observed during the early follicular phase. In the two normal men, the LH values obtained with RRA were higher than those obtained with RIA. It is concluded that the LH RRA is a practical and efficient tool for clinical research.     

High preovulatory serum luteinizing hormone level is unfavorable to conception.

Serum estradiol, progesterone and luteinizing hormone (LH) levels of 16 pregnant and 58 non-pregnant stimulated in vitro fertilization-embryo transfer (IVF-ET) or gamete intrafallopian transfer (GIFT) cycles have been compared with regard to their predictive value for achievement of pregnancy. Serum estradiol and progesterone pattern of the pregnant and non-pregnant group did not show any significant difference. Around the time of ovulation induction by human chorionic gonadotropin (hCG) the serum LH values proved to be higher in the non-pregnant group than in the pregnant one. In spite of having a permissive function, preovulatory serum estradiol and progesterone seem not to have a predictive value with regard to pregnancy. Elevated preovulatory serum LH is detrimental for pregnancy, therefore the measurement of serum LH beyond hCG administration also, and the cancellation of cycles with high serum LH levels shortly before oocyte retrieval is recommended.     

Evaluation of testicular function in prepubertal boys by means of the luteinizing hormone-releasing hormone test.

Luteinizing hormone (LH)-releasing hormone (LH-RH) tests (50 microgram/sq m intravenously) were performed in 112 prepubertal boys ages 13/12 to 11 years (mean +/- standard deviation, 75/12 +/- 16/12 years) suspected of having a testicular disorder because of improperly located testes (77 boys) or hypogonadism (35 boys). Four of the patients were retested within a period ranging from 6 to 16 months. Of the 112 boys tested, 17% were found to have high basal levels of follicle-stimulating hormone (FSH) and 23% were found to have an abnormally high release of FSH after LH-RH administration. Only three patients had abnormally high basal levels of LH and/or elevated LH responses to LH-RH. The basal plasma testosterone levels were found to be normal in all 112 bosy. The fact that plasma FSH levels were elevated more often than LH levels suggests that the tubular elements are damaged more frequently than are the Leydig cells. The surprisingly high incidence of an abnormal response of plasma FSH to LH-RH in boys with mobile testes calls for an increased awareness of the importance of regular examination of these patients until full puberty has been achieved. It is concluded that determination of basal plasma FSH levels and the response to LH-RH stimulation is a useful diagnostic tool for evaluating testicular function in prepubertal boys with suspected pathology of the testes.     

Hypothalamic-pituitary-gonadal axis in thalassemic patients with secondary amenorrhea

Eight thalassemic patients, aged 24-35 years, who developed amenorrhea 2-15 years after menarche, were studied. Mean basal serum LH and FSH levels and the peak levels after gonadotropin-releasing hormone were significantly less than corresponding values in normal controls. All patients showed low basal serum levels of estradiol and six had a poor or absent response to human menopausal gonadotropin. One subject had intact pituitary-gonadal function and one patient had an impaired LH and FSH response to gonadotropin-releasing hormone in the presence of a significant increase of estradiol after human menopausal gonadotropin stimulation. The findings regarding pituitary hormones other than gonadotropins suggest that iron overload damages tropic cells unequally and inconsistently. We conclude that both pituitary and gonadal damage may be responsible for the secondary amenorrhea in thalassemic patients.