Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women

The effects of hormone replacement therapy (HRT) on the central nervous system in postmenopausal women might be mediated by changes in neurosteroid synthesis and/or release. The aim of this study was to evaluate the impact of HRT on the levels of allopregnanolone ,a sedative anxiolytic GABA_A agonist steroid ,and dehydroepiandrosterone (DHEA) ,a GABA_A antagonist steroid. We evaluated allopregnanolone and DHEA circulating levels after 1 ,3 ,6 ,9 and 12 months of HRT with ten different estrogen or estrogen-progestin molecules ,regimens and routes of administration in 186 postmenopausal women. Cortisol ,luteinizing hormone ,follicle stimulating hormone ,estradiol and progesterone levels were also evaluated. Allopregnanolone levels significantly increased during follow-up with all HRT preparations. The addition of progestin molecules (except for 19-nor derivatives) to transdermal estradiol administration alone determined a higher increase in allopregnanolone levels. Transdermal HRT showed a significantly higher percentage change in allopregnanolone levels compared with oral HRT. DHEA levels showed a progressive decline starting from the 3-month follow-up ,without significant differences between the transdermal and oral groups ,as well as among the ten groups ,independently of the presence and type of progestin molecule used. In conclusion ,HRT strongly modifies circulating neurosteroid levels in postmenopausal women.     

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.     

Gamma‐aminobutyric acidA receptor agonist,muscimol, increases KiSS‐1 gene expression in hypothalamic cell models

Purpose

Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic–pituitary–gonadal (HPG) axis. In this study, the direct action of the gamma‐aminobutyric acid (GABA)_A receptor agonist on kisspeptin‐expressing neuronal cells was examined.

Methods

A hypothalamic cell model of rat hypothalamic cell line R8 (rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABA_A receptor agonist, muscimol, to determine the expression of the KiSS‐1 gene.

Results

Stimulation of the rHypoE8 cells with muscimol significantly increased the level of KiSS‐1 messenger (m)RNA expression. The ability of muscimol to increase the level of KiSS‐1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol‐induced increase in KiSS‐1 mRNA expression was completely inhibited in the presence of the GABA_A receptor antagonist. Although muscimol increased the expression of KiSS‐1, the natural compound, GABA, failed to induce the expression of KiSS‐1 in the rHypoE8 cells. Muscimol did not modulate gonadotropin‐releasing hormone expression in either the rHypoE8 cells or the primary cultures of the fetal rat brains.

Conclusions

This study's observations suggest that the activation of the GABA_A receptor modulates the HPG axis by increasing kisspeptin expression in the hypothalamic neurons.     

Endocrine response to pregnanolone

Neuroendocrine effects of the neurosteroids, pregnanolone and allopregnanolone have been demonstrated in rats. The endocrine effects of pregnanolone in humans have so far not been fully elucidated. This study has evaluated the effects of pregnanolone administration on part of the hypothalamus–pituitary–gonadal (HPG) axis throughout the menstrual cycle in control subjects and patients with premenstrual syndrome (PMS). Intravenous pregnanolone and vehicle were given to eight women with, and eight women without, PMS during the mid-follicular and late luteal phase. Following the drug administrations, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin plasma levels were measured.

Intravenous pregnanolone induced a rise in progesterone levels in the follicular phase. In the luteal phase progesterone levels decreased in response to pregnanolone provocation. Pregnanolone did not induce any changes in estradiol, LH, FSH or prolactin plasma levels in either cycle phase. PMS patients and control subjects did not differ with respect to the endocrine effects of pregnanolone.

In conclusion, our data show that pregnanolone, in moderate doses, appears not to have any adverse effects on the HPG axis, irrespective of cycle phase.     

Ovarian reserve in young women with low birth weight and normal puberty: a pilot case–control study

Aim.?Studies indicate that women born small for gestational age (SGA) have impaired ovarian function. The origin of this ovarian dysfunction is still debatable. The aim of this study was to compare ovarian ageing between girls born appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Müllerian hormone (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing hormone (GnRH) in adolescent girls born SGA and AGA.

Methods.?A case–controlled pilot study consisting of seven SGA women (birth weight?<10th percentile AGA) and 13 AGA women with regular menstrual cycles, age 19.9 (±0.42). Early follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline samples, 100?μg GnRH was administered intravenously and at 30, 60 and 90?min blood samples were taken to measure gonadotropin levels and to compute the response to endogenous GnRH.

Results.?Mean follicular phase LH, FSH, E2 and AMH levels did not significantly differ between young women born SGA and AGA. Furthermore, the response to endogenous GnRH showed no significant differences either.

Conclusions.?We concluded against extension of this pilot study. Based on our observations it seems unlikely that limited ovarian reserve is a predominated problem in adolescent SGA.     

Effects of cetrorelix,a GnRH-receptor antagonist,on gonadal axis in women with functional hypothalamic amenorrhea

Background.?Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility.

Methods.?We studied the effects of a GnRHa, cetrorelix (CTX 3.0?mg), in six women with HA (age 30.7?±?3.2 years; BMI 21.5?±?1.7 kg/m²) and six control subjects (CS, 28.2?±?0.6 years; 22.6?±?0.9 kg/m²) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4?h (08.00–12.00 am) before, +24?h and +96?h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72?h after CTX.

Results.?CS: CTX reduced (p?<?0.05) LH, FSH, and oestradiol (nadir at +12?h, +24?h, and +24?h); LH rebounded at +96?h, FSH and oestradiol recovered at +48?h and +72?h. The 4-h evaluation showed LH and FSH reduction (p?<?0.05) at +24?h, with LH rebound at +96?h. HA: CTX reduced (p?<?0.05) LH, FSH, and oestradiol, (nadir at +24?h, +48?h, and +48?h, recovery at +48?h, +72?h, and +96?h). The 4-h evaluation showed gonadotropin reduction (p?<?0.05) 24?h after CTX, without any rebound effect.

Conclusions.?One single CTX dose still modulates gonadotropin secretion in HA. Its ‘paradoxical’ stimulatory effect on gonadotropins needs to be verified after prolonged administration.     

Hormonal replacement therapy in women with Turner's syndrome in Poland: Analysis of 176 cases

Aim.?Turner syndrome (TS) is one of the forms of gonadal malfunction. The study aims at the analysis of hypophysis-gonad axis (HGA) of women with TS who use and do not use hormonal replacement therapy (HRT).

Method.?One hundred and seventy-six Poles with TS were investigated in the years 1995–2004. The information about the application of HRT was given during the interview. The HGA was examined by the estimation of gonadotropin (FSH, LH) and 17β-estradiol (E₂) levels.

Results.?HRT was administered to 89% of women with TS at some point of their life. However, at the time of writing this report only 54% of them have been taking this drug. The variety of hormonal preparations used by the patients was great. In women with TS using the HRT, in contradiction to women with TS who do not use it, lower concentrations of FSH (32.1 ± 22.1 vs. 44.2 ± 23.3 IU/l) and LH (20.8 ± 17.5 vs. 26.6 ± 18.1 IU/l) as well as higher level of E₂ (135.5 ± 147.9 vs. 89.9 ± 100.6 pmol/l) were observed. The negative correlation between E₂ and FSH levels was not observed in women with TS using HRT, despite the elevation of 17β-estradiol levels and the reduction of gonadotropin concentration.

Conclusions:?(1) Large percentage of women with TS does not use HRT. (2) Women with TS, who receive HRT, use this method of treatment insufficiently.     

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.     

Ovulation triggering in clomiphene citrate-stimulated cycles: Human chorionic gonadotropin versus a gonadotropin releasing hormone agonist

Purpose To compare the use of human chorionic gonadotropin (hCG) to a gonadotropin releasing hormone (GnRH) agonist, nafarelin, in initiating ovulation and supporting the luteal phase after priming with clomiphene.Methods In 26 infertile women 50 mg clomiphene citrate produced a preovulatory-size follicle. Then, 11 women were randomized to receive two 400-g doses of nafarelin intranasally 16 h apart, and 15 women were injected intramuscularly with 5000 IU of hCG (luteal day 0 = LD0). Starting on LD6, 7 more 400-g doses of nafarelin were repeated on an every 16-h schedule or a single 2500 IU dose of hCG was given, respectively. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), progesterone (P), and hCG were measured. On LD13, endometrium was evaluated with ultrasonography and biopsy in 19 nonpregnant women.Results As judged by a threefold rise in serum LH, an LH surge was detected on LD1 in all 11 nafarelin patients, but in only 8 hCG patients (P = 0.01). LH and FSH levels were significantly higher on LD1, 7, and 8 and were significantly suppressed on LD13 in the nafarelin group. All patients had mid-luteal P levels greater than 10 ng/ml and luteal phases longer than 13 days. Significantly different luteal E₂ or P levels were noted only on LD13, with lower values in the nafarelin group. Pregnancies were achieved in 3 of 11 nafarelin cycles and 2 of 15 hCG cycles. Luteal phase defects were also similar: 4 of 8 nafarelin patients and 7 of 11 hCG patients.Conclusion Nafarelin or hCG in conjunction with clomiphene can result in viable pregnancies, but is associated with low pregnancy rates and a high incidence of luteal phase defects.     

Polycystic ovary syndrome or hyperprolactinaemia: a study of mild hyperprolactinaemia

Polycystic ovary syndrome (PCOS) and hyperprolactinaemia are both common causes of secondary amenorrhoea in reproductive women. The relationship between PCOS and hyperprolactinaemia has been reported with controversial results. To evaluate the clinical and laboratory features of women with mild hyperprolactinaemia and PCOS, we studied 474 Taiwan Chinese women: 101 had mild hyperprolactinaemia, 266 had PCOS and 107 were the control group. In this study, we found that 64% of the women with mild hyperprolactinaemia fulfilled the PCOS diagnostic criteria, regardless of their prolactin levels. Obese women with PCOS had significantly lower luteinising hormone (LH) and LH-to-FSH ratios than non-obese women with PCOS. Obese hyperprolactinaemic women had significantly lower follicle-stimulating hormone (FSH), but higher LH-to-FSH ratios than the non-obese hyperprolactinaemic women. For women with PCOS, the BMIs were significantly negative with LH (γ?=??0.253, p?<?0.001), but not with FSH (γ?=??0.061, p?=?0.319). For the hyperprolactinaemic women, the BMIs were significantly negative with FSH (γ?=??0.353, p?<?0.001), but not with LH (γ?=??0.021, p?=?0.837). Although PCOS-related syndrome was very prevalent in women with hyperprolactinaemia, the patterns of disturbance in gonadotropin secretion were different between the PCOS and the hyperprolactinaemia patients.     

Serum luteinizing hormone,follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction

Gonadotrophin-releasing hormone analogues (GnRH-a) are used widely in controlled ovarian stimulation (COS) cycles for assisted reproduction. At present, there is great debate about the influence of exogenous hormone activity on the hypothalamus–pituitary axis following pituitary desensitization. The objective of this comparative study was to investigate the pattern of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol in women undergoing ovarian stimulation with different GnRH-a preparations. We retrospectively analysed 201 women, aged between 27 and 43 years, who were referred consecutively to our infertility clinic between January 2002 and January 2003. All women had no endocrinopathies or occult ovarian failure as assessed by day-3 hormone profile. Women were enrolled in one of the following COS protocols: depot triptorelin long protocol (n?=?38), buserelin long protocol (n?=?101) or buserelin short protocol (n?=?62). Recombinant FSH was used to induce ovulation. Treatment was monitored by transvaginal ultrasound scan and serum measurement of FSH, LH and oestradiol. Among the women initially included, 30 had cancelled cycles due to poor ovarian response. Serum LH levels were significantly higher in the short-protocol group compared with the long-protocol groups (p?<?0.001). The number of follicles, oocyte yield, number of grade-I embryos and fertilization rate were significantly lower in the short-protocol group than in the long-protocol groups. These findings showed that LH concentrations are significantly higher in women undergoing reversible medical hypophysectomy with a GnRH-a short protocol than in women treated with a long protocol. The hypothesis of an LH ceiling is confirmed.     

The ovarian response to standard gonadotropin stimulation is influenced by AMHRII genotypes

The aim of the current study was to explore whether anti-Müllerian hormone receptor II (AMHRII) genetic variants influence the hormonal profile and the ovarian response to standard gonadotropin stimulation of women undergoing medically assisted reproduction. Three hundred in vitro fertilization or intracytoplasmic sperm injection patients constituted the study population, while 300 women with at least one spontaneous pregnancy participated as controls. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂) and AMH levels were determined at the third day of the menstrual cycle. AMHRII 10A?>?G (rs11170555), 1749C?>?T (rs2071558) and ?482A?>?G (rs2002555) polymorphisms were genotyped. The follicle and oocyte numbers, the follicle size and the clinical pregnancies were recorded. Regarding the AMHRII 1749C?>?T polymorphism, 1749CT women presented with higher total follicle and small follicle numbers compared to 1749CC women (p?=?0.04 and p?=?0.01, respectively). Whereas, as concerns the ?482A?>?G polymorphism, ?482AG women were characterized by higher total follicle and small follicle numbers comparing with ?482AA women (p?=?0.07 and p?=?0.004, respectively). Finally, ?482AG women presented with increased FSH levels compared to ?482AA women (p?AMHRII gene polymorphisms with serum AMH levels or clinical pregnancy rates were observed. AMHRII 1749C?>?T and ?482A?>?G genetic variants were associated with the ovarian response to standard gonadotropin stimulation, affecting mainly the follicular growth.     

Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects

The pathogenesis of primary dysmenorrhea is still poorly understood. The objective of the present investigation was to study differences in plasma concentrations of reproductive hormones in women with primary dysmenorrhea vs. healthy controls. In a prospective, parallel-group study we determined the plasma concentrations of oxytocin, vasopressin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (17β-E₂), progesterone and prostaglandin F_2α metabolite (15-keto-13,14-dihydro-PGF_2α) over one menstrual cycle in eight women with primary dysmenorrhea and eight healthy volunteers. In dysmenorrheic women the plasma concentration of oxytocin was significantly higher at menstruation (p = 0.0084) and that of vasopressin significantly lower at ovulation (p = 0.0281) compared with healthy women. They had also higher FSH levels in the early follicular phase (p = 0.0087) and at menstruation (p = 0.0066) and the 17β-E₂ concentration was higher in the late follicular phase (p = 0.0449). No differences were seen for LH, progesterone and PGF_2α metabolite. The differences of oxytocin, vasopressin, FSH and 17β-E₂ concentrations found in plasma suggest an involvement of these hormones in mechanisms of primary dysmenorrhea. These mechanisms seem to be mainly regulated through the hypothalamus and pituitary. The influence of oxytocin on the non-pregnant uterus seems to be more important than earlier believed.     

Effects of cyproheptadine clorhydrate,a serotonin receptor antagonist,on endocrine parameters in weight-loss related amenorrhea

The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic, underweight ,amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours ,sampling every 10 minutes) and a naloxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH) ,follicle-stimulating hormone (FSH) ,growth hormone (GH) ,estradiol ,thyroid-stimulating hormone (TSH) ,free tri-iodothyronine (fT₃) ,free thyroxine (fT₄) and total triiodothyonine (total T₃) ,insulin-like growth factor-I (IGF-I) concentrations were determined. Pulse detection analysis was performed using the DETECT program. Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index (BMI) did not vary; conversely ,integrated mean gonadotropins ,GH and fT₃ concentrations increased during the treatment. In conclusion ,cyproheptadine administration affects some of the abnormal endocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT₃ increases take place owing to a change in the metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling food intake at the hypothalamic level.     

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.     

Metformin administration restores allopregnanolone response to adrenocorticotropic hormone (ACTH) stimulation in overweight hyperinsulinemic patients with PCOS

Objective.?To investigate the adrenal response in terms of allopregnanolone secretion in a group of hyperinsulinemic patients with polycystic ovary syndrome (PCOS).

Design.?Controlled clinical study.

Setting.?Patients with PCOS in a clinical research environment.

Patients.?Twenty-two overweight patients with PCOS with hyperinsulinism were enrolled after informed consent.

Interventions.?All patients underwent hormonal evaluations, oral glucose tolerance test (OGTT) and adrenocorticotropic hormone (ACTH) test before and after 4 months of metformin administration (500 mg p.o. bi-daily). Ultrasound examinations and Ferriman-Gallway score were also performed. Main outcome measures. plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), estradiol, 17-hydroxy-progesterone (17OHP), androstenedione (A), testosterone (T), allopregnanolone, glucose, insulin, C peptide concentrations, body mass index (BMI).

Results.?Metformin administration reduced significantly LH, A, T, insulin and BMI, while allopregnanolone was significantly increased with no change in progesterone plasma levels. Insulin response to OGTT decreased and allopregnanolone response to ACTH stimulation before while this was restored after the treatment interval. The Ferriman-Gallway score as well as the ovarian volume was significantly decreased after 4 months of metformin therapy.

Conclusions.?In overweight patients with PCOS with hyperinsulinism, allopregnanolone secretion is impaired and metformin administration restored normal allopregnanolone concentrations modulating both steroid syntheses from the ovaries and from adrenal gland.     

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.     

Endocrine response to pregnanolone.

Neuroendocrine effects of the neurosteroids, pregnanolone and allopregnanolone have been demonstrated in rats. The endocrine effects of pregnanolone in humans have so far not been fully elucidated. This study has evaluated the effects of pregnanolone administration on part of the hypothalamus-pituitary-gonadal (HPG) axis throughout the menstrual cycle in control subjects and patients with premenstrual syndrome (PMS). Intravenous pregnanolone and vehicle were given to eight women with, and eight women without, PMS during the mid-follicular and late luteal phase. Following the drug administrations, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin plasma levels were measured. Intravenous pregnanolone induced a rise in progesterone levels in the follicular phase. In the luteal phase progesterone levels decreased in response to pregnanolone provocation. Pregnanolone did not induce any changes in estradiol, LH, FSH or prolactin plasma levels in either cycle phase. PMS patients and control subjects did not differ with respect to the endocrine effects of pregnanolone. In conclusion, our data show that pregnanolone, in moderate doses, appears not to have any adverse effects on the HPG axis, irrespective of cycle phase.     

基础FSH/LH比值对预测年轻不孕患者IVF-ET周期卵巢反应性的影响

目的:探讨基础FSH和LH比值预测基础FSH水平正常且年轻不孕患者卵巢反应性的临床价值。方法:回顾分析2004年6月至2005年5月因男方因素或输卵管因素行体外受精-胚胎移植(in-vitrofertilization-embryotransfer,IVF-ET)治疗的年轻(年龄≤35岁)且基础FSH水平正常(≤8.5IU/L)不孕患者237例的临床资料,共计237个治疗周期,依据FSH/LH不同比例分为3组,A组(n=44)FSH/LH<1;B组(n=143)FSH/LH12;C组(n=50)FSH/LH>2。比较各组间的年龄、激素水平、卵巢反应、IVF的实验室结果以及妊娠情况。结果:3组患者的年龄、窦卵泡数、基础E2值、受精率、卵裂率和妊娠率两两相比无统计学差异(P>0.05),但A、B两组间的基础FSH值、基础LH值、E2峰值和成熟卵泡数差异有统计学意义(P<0.05);A、C两组间基础FSH值、基础LH值、E2峰值、促性腺激素(gonadotropin,Gn)总用量、Gn平均每日用量、Gn用药时间及获卵数和成熟卵泡数的差异有统计学意义(P<0.05);B、C两组间基础LH值、E2峰值、促性腺激素总用量、Gn平均每日用量和Gn用药时间比较也有明显差异(P<0.05)。结论:FSH正常的年轻妇女,FSH/LH>2的卵巢反应性明显低于FSH/LH<1者;FSH/LH比值是预测基础FSH正常且年轻不孕者卵巢反应性的一项较好指标。     

High levels of serum allopregnanolone in women with premature ovarian failure

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects.

In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of Δ4 precursor (dehydroepiandrosterone sulfate (DHEAS)), A5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and infertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.