Gonadotropin levels in Turner's syndrome: correlation with breast development and hormone replacement therapy

We conducted a study of the basal levels of gonadotropins in 38 patients with Turner's syndrome ,14 of whom were using hormone replacement therapy (HRT). The gonadotropin levels were compared with pubertal development and HRT. Seven patients had presented spontaneous menarche; five patients maintained their periods and normal gonadotropin levels ,and two developed secondary amenorrhea and high gonadotropin levels. The majority of patients on HRT had high gonadotropin levels. Follicle stimulating hormone (FSH) levels were significantly lower (p = 0.001) in patients with breast development at stage 5, regardless of whether the patient had undergone a spontaneous or a hormonally induced puberty. We concluded that gonadotropin levels are normal in those patients with spontaneous periods ,and are high in most patients on HRT; and that FSH levels are significantly lower in those patients with breasts at stage 5.     

GnRH analogues as an adjuvant therapy for ovarian cancer patients.

OBJECTIVES: Lowering gonadotropin levels with gonadotropin-releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. METHODS: The study group comprised 69 patients aged 27-70 years, stratified according to the type of treatment. The overall disease-free, 5-year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. RESULTS: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. CONCLUSIONS: Combined therapy can produce favorable results in late-stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.     

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

Serum follicle-stimulating and luteinizing hormone and progesterone in single and multiple gestations following induction of ovulation

At the Mount Sinai School of Medicine in New York, researchers followed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone in 5 women treated with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) for induction of ovulation. A total of 7 treatment cycles were followed. In 5 of the cycles conception occurred. Values in the 5 cycles in which conception occurred were dissimilar to values in normal menstrual cycles. Thus, efforts to mimic normal gonadotropin elaboration are probably unnecessary in the treatment of anovulatory women. Significant variation in values occurred among the patients. A midcycle FSH peak concomitant with the LH surge was clearly seen to be unnecessary for ovulation induction. Following ovulation a general decline in FSH occurred. FSH apparently was suppressed during the gestational period. In patients who had elevated pretreatment serum LH levels, LH apparently was suppressed during the first 1/2 of the HMG therapy; however, during the latter 1/2 of the HMG therapy, LH rose in these patients. Therapy-induced multiple ovulation with resultant multiple corpora lutea caused serum progesterone levels to rise to 2-3 times those of normal singleton gestations. Implantation appeared to have occurred 8-9 days after ovulation induction. The 5 pregnancies resulted in 3 term deliveries, 1 first-trimester spontaneous abortion, and a quadruplet premature delivery.     

High FSH:LH ratio and low LH levels in basal cycle day 3: impact on follicular development and IVF outcome

Purpose: To examine the impact of low basal cycle day 3 serum LH levels or a high FSH:LH ratio on IVF results. Methods: A homogeneous group of patients was analyzed as identified by normal basal cycle of follicle stimulating hormone (FSH), Luteinizing hormone (LH), and estradiol (E₂) levels. High responders (high LH:FSH ratio) and low responders (high FSH or E₂ levels, and women 42 years of age) were excluded from analysis. Only cycles stimulated with a combination of a GnRHa (luteal suppression) and pure FSH were studied. Results: Patients with low basal LH levels (<3 mIU/mL) did not differ significantly from controls in terms of response to controlled ovarian hyperstimulation but there was a clear trend toward poorer implantation and clinical pregnancy rates. On the other hand, patients with a high FSH:LH ratio (<3) had significantly fewer mature oocytes aspirated, and lower implantation and clinical pregnancy rates than patients with gonadotropin ratio 3. These negative effects were evident in the presence of normal basal FSH levels and after adequate matching of female's age and number of embryos transferred. Conclusions: These studies highlight a negative impact of a basal cycle high FSH:LH ratio (and possibly low LH levels) on follicular development and oocyte quality in these patients subjected to pituitary down-regulation followed by pure FSH administration. A high FSH:LH ratio may be therefore used as an early biomarker of poor ovarian response.     

Ovarian stimulation for in vitro fertilization in low-responder patients using pulsatile intravenous follicle stimulating hormone

There is a subset of patients who fail to respond adequately to exogenous gonadotropin stimulation for in vitro fertilization (IVF). In this study, six such low-responder patients who had inadequate stimulations with high-dose intramuscular (im) follicle stimulating hormone (FSH) were treated in a subsequent cycle with pulsatile intravenous (iv) FSH. A paired analysis was performed to compare the cycles using high-dose im FSH with those using pulsatile iv FSH. Trough serum FSH levels were significantly higher with pulsatile iv FSH. No significant difference was noted in the stimulation characteristics or the number or quality of oocytes retrieved and embryos transferred. No pregnancies occurred in either group. While pulsatile iv administration of gonadotropin increases serum FSH levels, it does not appear to have a major impact on follicular stimulation or outcome in low-responder patients undergoing IVF.     

Decrease in luteal gonadotropin concentration in conception cycles after in vitro fertilization/gamete intrafallopian transfer

The concentrations of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in the luteal phase of the cycle in patients undergoing ovarian hyperstimulation. In nonconception cycles, FSH and LH were increased in the late luteal phase compared with conception cycles in which both gonadotropins were suppressed. Estradiol (E2) and progesterone concentrations increased in pregnancy cycles and may be the sole cause for the decreased gonadotropin concentrations as shown by equivalent concentrations of LH and FSH in both pregnancy and nonpregnancy cycles after matching for E2 concentrations. Subjects who subsequently had twin pregnancy or a spontaneous abortion were compared with those with a successful ongoing singleton conception. There were no significant differences relative to LH and FSH between the three groups, although in twin pregnancy FSH tended to be lower at day 16 from oocyte recovery. It is concluded that suppression of LH and FSH in hyperstimulated pregnancy cycles occurs after the time of the rising human chorionic gonadotropin concentrations in plasma.     

Spontaneous luteinizing hormone (LH) surges are associated with more rapidly increasing estradiol (E2) and follicle stimulating hormone (FSH) in in vitro fertilization and embryo transfer

In a retrospective analysis of 64 patients stimulated with human menopausal gonadotropin (hMG) and/or pure follicle stimulating hormone (FSH); 35 cycles with spontaneous luteinizing hormone (LH) surges were compared with 29 control cycles with respect to serum FSH and estradiol (E₂) levels drawn on the day prior to and the day of human chorionic gonadotropin (hCG), approximately 16 hr after gonadotropin stimulation. FSH decreased significantly (P<0.05) in control cycles where two or more preovulatory oocytes (preovs) were obtained, in contrast to cycles with a spontaneous LH surge, where FSH increased irrespective of the number of preovs. The E₂ increase in the LH surge cycles was significantly higher (P<0.05) than in the control cycles. However, the increase in E₂ did not correlate with the change in FSH levels or with the number of preovs.     

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.     

Characteristics of ovarian follicles in spontaneous and stimulated cycles in which there was an endogenous luteinizing hormone surge

The growth of ovarian follicles was assessed with the use of ultrasound in spontaneous cycles and in cycles stimulated with clomiphene citrate (CC) alone, CC plus pulsatile human menopausal gonadotropin, and CC plus pulsatile follicle-stimulating hormone (FSH). At the time of the onset of the luteinizing hormone surge (LH), the size of the leading follicle did not differ significantly between the spontaneous and the stimulated cycles, although it was larger in the CC/FSH cycles. During the two days before the LH surge onset, the growth rate was faster in the stimulated than the spontaneous cycles. It is suggested that despite the provocation of extremely high plasma-estradiol levels and multiple follicular development, the leading follicle in stimulated cycles ovulated at a size equal to or greater than that in spontaneous cycles. The reason for the higher follicle size in the CC/FSH cycles is, as yet, unclear.     

Ovarian hyporesponsiveness in combined gonadotropin-releasing hormone agonist and menotropin therapy is associated with low serum follicle-stimulating hormone levels.

The study was designed to evaluate if ovarian hyporesponsiveness, which is associated with combined gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) therapy is because of suboptimal serum follicle-stimulating hormone (FSH) levels. Two groups of 12 patients each were suppressed with GnRH-a and stimulation with a fixed dose of hMG. The control group (n = 10) received equal doses of hMG only. The follicular phase and the number of hMG ampules was significantly higher in the study group. Basal FSH levels and FSH levels during hMG treatment were significantly lower in patients treated with GnRH-a. Peak estradiol levels and the outcome of in vitro fertilization treatment were similar in the three groups. We suggest that the delay in ovarian response in patients treated with a combination of GnRH-a and hMG is because of lack of endogenous contribution of FSH, resulting in low circulating levels of FSH. An increase of serum FSH levels by administration of higher doses of hMG can reverse this effect.     

Serum follicle-stimulating hormone level is a predictor of bone mineral density in patients with hormone replacement therapy

Methods A retrospective study regarding the relationship between serum hormonal levels and bone mineral density (BMD) was performed in 125 women with hormone replacement therapy (HRT). Serum estradiol (E₂), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and BMD were evaluated before and at 12 and 24 months of HRT.Results There was a significant increase in E₂ and decrease in FSH at both 12 (E₂, 39.3±76.6 pg/ml to 71.0±67.9 pg/ml; FSH, 67.9±36.3 mIU/ml to 47.9±29.0 mIU/ml) and 24 months (E₂, 68.3±54.5 pg/ml; FSH, 45.3±24.4 mIU/ml). LH level was high at baseline (26.5±16.1 mIU/ml) and decreased at 12 months (22.9±14.0 mIU/ml). On the contrary, it increased from 12 to 24 months (27.4±14.9 mIU/ml). In the lumbar spine BMD, a significant rise was seen only in the first 12 months (0.933±0.157 g/cm² to 0.938±0.152 g/cm²). When percentage change was analyzed, a significant positive correlation was found between E₂ and BMD and a negative correlation between gonadotropin levels and BMD.Conclusion These data demonstrate that serum gonadotropin levels, especially FSH, are a good marker to predict BMD in women with HRT.     

Follicular atresia associated with concurrent initiation of gonadotropin-releasing hormone agonist and follicle-stimulating hormone for oocyte recruitment

The ability of gonadotropin-releasing hormone agonist (GnRHa) to cause an initial stimulation of serum gonadotropins was used for follicular recruitment for in vitro fertilization (IVF) in 12 patients with a history of low estradiol (E2) response to conventional gonadotropin stimulation. Stimulation was initiated on cycle day 3 with concurrent administration of leuprolide (1 mg/day subcutaneously) and follicle stimulating hormone (FSH, 4 ampules/day intramuscularly). An 8-fold increase in basal serum luteinizing hormone (LH) and a 4-fold increase in basal serum FSH was seen on cycle day 4. Serum progesterone levels rose significantly by day 6. When compared to prior IVF attempts in these patients, the mean day of human chorionic gonadotropin administration and corresponding E2 levels were not significantly different. More atretic oocytes and fewer preovulatory oocytes were retrieved using GnRHa, and no increase was seen in total oocytes retrieved. One patient was canceled for poor E2 response, and one patient conceived, with a current viable pregnancy. It is concluded that concurrent initiation of leuprolide and FSH stimulation on cycle day 3 in patients with prior low response does not improve oocyte recruitment, and the high LH environment generated from initial stimulation of the agonist may be detrimental to normal oocyte development.     

Estrogen replacement therapy in postmenopausal women: a study of the efficacy of estriol and changes in plasma gonadotropin levels.

The purpose of this study was to clarify the efficacy of estriol for estrogen replacement therapy in postmenopausal women with undefined symptoms and to evaluate endocrinological changes during therapy in relation to clinical outcome. Administration of 2 mg estriol in 168 postmenopausal patients was markedly effective in 22.6% of cases, effective in 45.2%, fairly effective in 14.3%, and ineffective in 17.9% of cases. The plasma concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after administration of estriol decreased significantly (p < 0.001), by 52.2% and 32.9%, respectively for markedly effective cases, and by 39.1% and 48.0% for effective cases. In contrast, the plasma estradiol concentration remained unchanged. On the other hand, decreases in FSH and LH concentration were 13.9% and 5.9% for the fairly effective and 8.2% and 1.9% for ineffective cases, demonstrating a significantly lower decrease in plasma FSH and LH levels than in the markedly effective and effective cases (p < 0.001). For cases showing side-effects, the plasma FSH and LH levels decreased by 52.0% and 64.3%, respectively, whereas the plasma estradiol level remained unchanged. In conclusion, the efficacy of estriol was significantly correlated to the degree of decrease in plasma FSH and LH levels in patients with undefined symptoms. In addition, efficacy appeared to be correlated to the incidence of side-effects. The degree of reduction of FSH (39.1-52.2%) and LH (48.0-64.3%) from the baseline may possibly be used as a guide to the therapeutic hormone levels during HRT. The present results suggest that plasma gonadotropin levels could be a useful indicator in the management of patients undergoing estrogen replacement therapy.     

Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.     

The use of gonadotropins for the induction of ovulation in women with polycystic ovarian disease

Ten infertile patients with polycystic ovarian disease were treated with 18 cycles of "pure" human pituitary follicle-stimulating hormone (HP-FSH) and 10 cycles of human menopausal gonadotropin (HMG) consisting of FSH and luteinizing hormone (LH) in a 1:1 ratio. Human chorionic gonadotropin was used to trigger ovulation when optimal follicular development was achieved as judged by urinary estrogen determinations. Of the 18 cycles utilizing HP-FSH, 14 were presumptively ovulatory, 2 were conceptual, and in 5 cycles ovarian enlargement was noted. Of the 10 HMG cycles, none was ovulatory, no conceptions resulted, and 6 instances of hyperstimulation were noted. Pretreatment serum LH levels were significantly higher than normal follicular phase values. These observations suggest that endogenous LH levels in patients with polycystic ovaries are quite adequate for follicular development so that the administration of exogenous LH is unwarranted. Furthermore, the data suggest that HP-FSH or low-LH-containing HMG may prove to be an additional safe and effective nonsurgical treatment modality for patients who are anovulatory because of polycystic ovaries.     

Hormonal characteristics of women with clinical features of the polycystic ovary syndrome

The aim of the present study was to determine whether a group of patients selected on the basis of clinical features only is characterized by the typical hormonal findings as discussed in the literature concerning the PCO-syndrome. PCO patients had oligomenorrhea, secondary amenorrhea or otherwise evidence of chronic anovulation, as well as hirsutism and/or obesity. Control women had regular menstrual cycles and a normal body weight. Since androgen and estrogen production in women depends on the stage of follicular development, an effort was made to obtain endocrinological data under standardized conditions. Under well-defined circumstances the PCO group (n = 20) had higher LH levels and lower FSH levels as compared with the control group (n = 10). Consequently the LH/FSH ratio was significantly elevated in the PCO group. Serum estrone and estradiol levels were significantly elevated in the PCO group, as were the serum levels of androstenedione and testosterone. Despite these differences a marked degree of overlap existed in the PCO patients and the control women for gonadotropin, estrogen and androgen levels. It was concluded that although the presence of polycystic ovaries in the investigated PCO group of women was not confirmed by laparoscopy, laparotomy or histological examination of the ovaries, these women had basal endocrinological characteristics similar to those found in well-proven PCO patients reported in the literature.     

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition

Abstract

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.

Methods: A 52-year-old woman with a 2?months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173?ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.

Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.

Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.     

Elevation of follicular phase inhibin and luteinizing hormone levels in mothers of dizygotic twins suggests nonovarian control of human multiple ovulation

OBJECTIVE: To determine whether multiple ovulation in mothers of spontaneous dizygotic (DZ) twins is because of higher hypothalamic stimulation or is in response to lower serum levels of ovarian inhibin. DESIGN: Serum hormone levels were measured at five times throughout the cycle in a sample of eight mothers of DZ twins and paired controls. On day 12, ovarian ultrasonography was performed. SETTING: Blood samples were collected in participants' homes except on day 12 when they were collected at the ultrasonography clinic. PATIENTS, PARTICIPANTS: Human volunteers who had at least one set of spontaneous DZ twins were paired with controls matched for age and parity. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on approximate cycle days 1,2,8,12, and 21. RESULTS: Serum inhibin levels were elevated throughout the cycle (significantly on day 1) in mothers of DZ twins. Also elevated were early follicular FSH levels, LH levels throughout the follicular phase (significantly on days 1,2, and 8), and early to midfollicular E2 (significantly on day 8) in DZ mothers, indicative overall of greater follicular activity. CONCLUSION: It is concluded (1) that the primary cause of multiple ovulation in humans is not a decrease in inhibin secretion from the ovary; (2) the increased secretion of FSH and LH may be caused by elevated secretion of, or sensitivity to gonadotropin-releasing hormone; and (3) the elevated inhibin and E2 levels are a response to increased gonadotropin release.     

Predictive value of the FSH:LH ratio on follicular and luteal phase characteristics of the human menstrual cycle

A prospective study was designed to assess the predictive value of gonadotropin measurements obtained during the early follicular phase upon the hormonal characteristics of the subsequent cycle. The data obtained in 12 normal cycles were used to compute the mean and confidence interval (mean +/- 2 SEM) of the FSH:LH ratio, FSH and LH plasma levels. The limits of the confidence intervals for these different parameters were used to classify the patients. Data of 204 patients were analysed. Low FSH:LH ratios (less than 1.34) are associated with an increase in follicular phase length (+2.4 days), a lower ovulatory rate, but neither luteal phase length nor progesterone levels differ between these two groups. When patients are classified according to FSH levels, our results show that low FSH levels (less than 2.94 mIU/ml) are associated with longer follicular (+2.6 days) and shorter (-1.1 days) luteal phase lengths, but ovulatory rate and progesterone levels in the luteal phase of the ovulatory cycles are similar to those obtained in patients of the normal or high FSH group. High LH levels (greater than 3.15 mIU/ml) are associated with a decreased ovulation rate but follicular and luteal phase characteristics are similar to those obtained in patients in the normal or low LH group. In conclusion, low FSH: LH ratios and low FSH plasma levels measured in the early follicular phase of the cycle are associated with longer follicular phase lengths; but basal gonadotropin measurements have limited predictive value on luteal phase characteristics.