多囊卵巢综合征IGF-Ⅰ、IGFBP-1相关因素探讨

目的探讨多囊卵巢综合征(PCOS)患者胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合球蛋白-1(IGFBP-1)水平与肥胖、性激素、糖代谢各项指标之间的关系。方法测定31例PCOS研究组和29例健康对照组IGF-Ⅰ、IGFBP-1水平及肥胖、性激素、糖代谢各项指标,比较两组间差异;分析研究组IGF-Ⅰ、IGFBP-1水平与其他各项指标之间相关性。结果研究组IGFBP-1,性激素结合球蛋白(SHBG)低于对照组,体重指数(BMI),臀围比值(WHR),多毛评分(F-G评分),黄体生成素(LH),黄体生成素/卵泡刺激素(LH/FSH),总睾酮(T),游离睾酮(FT),雄烯二酮(A2),硫酸脱氢表雄酮(DHEAS),空腹胰岛素(FINS),胰岛素抵抗指数(HomaIR)高于对照组,差异均有显著性(P0.001～0.05),IGF-Ⅰ,FSH,雌二醇(E2),17羟孕酮(17-OHP),泌乳素(PRL),空腹血糖(FBG)差别无显著性(P0.05)。研究组中IGFBP-1与BMI呈负相关(r=-0.372,P0.05),与FINS呈负相关(r=-0.481,P0.01),与SHBG呈正相关(r=0.504,P0.01),IGF-Ⅰ与各指标之间无明显相关性。结论 IGFBP-1与PCOS患者肥胖、空腹胰岛素水平密切相关。     

Main inhibitor of follicle stimulating hormone in the luteal-follicular transition: inhibin A, oestradiol, or inhibin B?

The roles of oestradiol, inhibin A and inhibin B in the luteal-follicular transition were assessed by means of specific assays. Six premenopausal women were studied during a control and then a cycle treated with percutaneous oestradiol 0.1 mg/day from day 10 after the luteinizing hormone (LH) surge until day 4 of the following cycle. Inhibin A concentrations decreased similarly in control and treated cycles from day -5 to day 2, then increased in control cycle to 23.3 +/- 3.4 pg/ml on day 10 (mean +/- SEM). They remained low until day 5 in treated cycles and were lower than controls on day 10 (P < 0.01). Follicle stimulating hormone (FSH) concentrations increased on day 1 in controls and on day 5 in treated cycles when oestradiol concentration fell abruptly. Inhibin B concentrations remained low until day 1 in controls and day 4 in treated cycles. In both, inhibin B concentrations increased 1 day after FSH, peaking at 160 pg/ml. FSH concentrations began to plateau when inhibin B concentrations were >100 pg/ml and oestradiol concentrations below 200 pmol/l. These data suggest that inhibin A is not responsible for FSH suppression in the luteal phase and that the negative control of FSH shifts from oestradiol in the luteal phase to inhibin B in the mid-follicular phase.     

Sandostatin has no direct effect on ovarian steroidogenesis in vitro

Rat granulosa and theca—interstitial cells from immature,oestradiol-treated rats were isolated and incubated for 144h with follicle stimulating hormone (FSH), luteinizing hormone(LH), insulin alone or in combinations, and with two doses ofsandostatin (10^–7 M and 10^–6 M per culture). Oestradioland testosterone production by granulosa and theca—interstitialcells, respectively, was measured in culture media. The stimulatoryeffects of FSH alone and FSH with insulin but not insulin aloneon oestradiol production by granulosa cells were observed. Similarly,increased testosterone concentrations after treatment with LHalone and LH with insulin but not insulin alone were found inmedia from theca—interstitial cells. The addition of highor low doses of sandostatin to the cultures did not affect theproduction of oestradiol or testosterone. It was concluded thatsandostatin does not exert any direct effect on ovarian steroidogenesisin vitro.     

Serum androgen levels and insulin resistance in postmenopausal women: association with hormone therapy, tibolone and raloxifene

OBJECTIVE: To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy. METHODS: A total of 427 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Among them 84 were taking HT (46 women conjugated equine estrogens 0.625 mg; medroxyprogesterone acetate, 5 mg, CEE/MPA; and 38 women 17beta-estradiol 2 mg; norethisterone acetate 1 mg, E2/NETA); 83 were taking tibolone 2.5 mg; 50 were taking raloxifene HCl 60 mg; and 210 women were not receiving any therapy. Main outcome measures were FSH, LH, estradiol, total testosterone, SHBG, free androgen index (FAI), Delta4-Androstendione (Delta4-A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR). RESULTS: In women not on hormone therapy smoking and older age was associated with lower DHEAS levels. FAI values increased linearly with increasing BMI. Age and BMI were positive determinants of HOMA-IR, while no association was identified between endogenous sex steroids and insulin resistance. CEE/MPA therapy was associated with higher SHBG, lower FAI and lower HOMA-IR values compared to women not on therapy (age and BMI-adjusted SHBG: CEE/MPA 148.8 nmol/l, controls 58.7 nmol/l, p < 0.01; age-adjusted FAI: CEE/MPA 0.8, controls 3.2, p < 0.05; age-adjusted HOMA-IR: CEE/MPA 1.3, controls 2.6, p < 0.05). On the contrary, E2/NETA treatment had no effect on these parameters. Women on tibolone had lower SHBG, higher FAI and similar HOMA-IR values compared to controls (age and BMI-adjusted SHBG: 24.1 nmol/l, p < 0.01; FAI: 6.0, p < 0.05; HOMA-IR: 2.3, p = NS). Raloxifene users did not exhibit any difference with respect to sex steroids and HOMA-IR levels. CONCLUSIONS: CEE/MPA users had lower free testosterone and improved insulin sensitivity. Tibolone on the other hand associated with higher free testosterone, while raloxifene did not relate to any of these parameters.     

多囊卵巢综合征患者血清抑制素B水平的分析

目的：探讨抑制素B（inhibin,INH-B）水平在多囊卵巢综合征（PCOS）患者血清中的变化及其与体重指数（BMI）的关系。方法：筛选PCOS患者40例,根据体重指数（BMI）分为肥胖组和非肥胖组并检测血清中的抑制素B（INH-B）、胰岛素生长因子-I（IGF-I）、空腹胰岛素（In）、瘦素（leptin）、黄体生成素（LH）、卵泡刺激素（FSH）、人体催乳素（PRL）、雌二醇（E2）和睾酮（T）,另取40例排卵正常、无怀孕妇女做对照分析。结果：PCOS患者肥胖组leptin、In、LH、T水平明显高于非肥胖组,INH-B、IGF水平则明显低于非肥胖组,差异有统计学意义（P〈0.05）;且肥胖组的LH与INH-B呈负相关（r=-0.735,P〈0.05）,非肥胖组的LH与INH-B无明显相关性。非肥胖组INH-B、IGF、LH、T水平明显高于对照组,差异有统计学意义（P〈0.05）。结论：INH-B与多囊卵巢综合征（PCOS）发生有关,且作为PCOS特征的肥胖又影响着INH-B的作用和水平。     

Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH

There has been much debate about the role of luteinizing hormone (LH) during follicle stimulating hormone (FSH)-treated ovarian stimulation for assisted reproduction, where the endogenous LH is suppressed using a gonadotrophin-releasing hormone analogue. The requirement for LH in oestradiol biosynthesis is established, but other effects of 'insufficiency' are less clear, and little attention has been paid to the specific origin of the FSH used. The aim of this study was to examine the roles of profoundly suppressed circulating LH concentrations in cycles of ovarian stimulation for IVF, which were affected in two large separate cohorts of patients undergoing assisted reproduction. They were stimulated by either purified urinary FSH (MHP) or recombinant human FSH (rFSH). Within each dataset, outcomes were examined with respect to the circulating concentrations of LH in the mid-follicular phase, as plasma samples were stored prospectively, and assayed retrospectively. Patients with profoundly suppressed LH showed much reduced oestradiol concentrations at mid-follicular phase and at human chorionic gonadotrophin administration in cycles treated with either MHP or rFSH. However, gross ovarian response, as became evident by FSH dose demands, duration of stimulation, and also oocyte and embryo yields and embryo cryopreservation were influenced only in cycles treated with MHP. Furthermore, no effect upon pregnancy survival was observed. Thus, it is concluded that there is a demand for additional exogenous LH treatment only in cycles treated with purified urinary FSH where the LH is profoundly suppressed.     

Birth weight and early socio‐economic disadvantage as predictors of sex hormones and sex hormone binding globulin in men at age 49–51 years

Objectives: A number of associations have been shown between early growth and later sex hormone levels in women, but less is known about this relationship in men. This study investigated lifecourse predictors of sex hormones in men in the Newcastle Thousand Families birth cohort. Methods: The Newcastle Thousand Families Study is a prospective study initiated in 1947. At age 49‐51 years, 574 study members returned detailed self‐completion questionnaires and 412 attended for clinical examination, including 172 men in whom blood samples were taken. Estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were measured. Free testosterone concentrations were also calculated. Results: Social class at birth independently predicted FSH and LH, with higher levels with increasing socioeconomic disadvantage. SHBG was higher with increasing standardized birth weight and lower with increasing contemporary body mass index (BMI). BMI also predicted LH, SHBG, and testosterone. None of the variables included within this analysis were significant predictors of estradiol. No other associations were seen with any of the variables included from across the lifecourse. Conclusions: Our findings suggest that birth weight may be positively associated with SHBG and early socioeconomic status may be related to FSH and LH in men. These novel findings are independent of contemporary BMI. Given the links between sex hormones, SHBG and disease outcomes such as type II diabetes and osteoporosis, it is possible that sex hormones may play a mediating role in the associations between circumstances in early life and later risk of chronic disease. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.     

Serum levels of insulin-like growth factor-1, IGF binding protein-1 and insulin and the response to human menopausal gonadotrophins in women with polycystic ovary syndrome

In order to determine which factors influence the large variationsin sensitivity to gonadotrophins witnessed in women with polycysticovary syndrome (PCOS), a prospective study was conducted ofthe correlation between basal clinical and endocrinologicalfeatures and gonadotrophin requirements of 20 women with clomiphene-resistantPCOS undergoing ovulation induction. Baseline evaluation ofserum concentrations of luteinizing hormone (LH), follicle stimulatinghormone (FSH), testosterone, fasting insulin, insulin-like growthfactor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-bindingglobulin (SHBG) were performed before administering gonadotrophin-releasinghormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin(HMG) was given in a standard individualized protocol accordingto ovarian response, until human chorionic gonadotrophin (HCG)was given. Serum concentrations of insulin, IGF-1, and IGFBP-1were unaffected by GnRHa. The BMI correlated positively withinsulin and inversely with IGFBP-1 serum concentrations andinsulin and IGFBP-1 were inversely correlated. The amount ofHMG required correlated positively with BMI and insulin concentrationsand inversely with IGFBP-1 in the whole group and these correlationswere maintained in the sub-group of lean women. No correlationwas observed between HMG requirements and IGF-1 or other hormones.Womenwith hyperinsulinaemia and low IGFBP-1 concentrations requiredsignificantly more HMG. Multiple regression analysis revealedthat insulin concentration is the most significant determinantof HMG requirement even when dissociated from BMI. We concludedthat requirement of HMG in PCOS is not merely determined byobesity but by a cardinal role of insulin concentrations which,when high, induce, hypothetically, a hyperandrogenic intrafollicularmilieu.     

Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents.

Hospital based studies have shown that oligomenorrhoeic adolescents have high luteinizing hormone (LH) and androgen concentrations, endocrine signs of polycystic ovary syndrome (PCOS). The prevalence of these abnormalities in an unselected population of adolescents is not known. We determined LH, follicle stimulating hormone (FSH), androstenedione, testosterone, dehydroepiandrosterone sulphate (DHEAS), oestradiol and prolactin concentrations in unselected population samples of adolescents with oligomenorrhoea, secondary amenorrhoea and regular menstrual cycles. A total of 2248 white, west European adolescents, aged 15.3 +/- 0.6 (mean +/- SD) years, participated. Blood was taken from 107 adolescents with regular menstrual cycles, 52 with oligomenorrhoea and four with secondary amenorrhoea. Oligomenorrhoeic adolescents had higher mean LH, androstenedione, testosterone, DHEAS and oestradiol concentrations compared with girls with regular menstrual cycles; 57% of the oligomenorrhoeic girls had LH or androgen concentrations above the 95th centile of adolescents with regular menstrual cycles. None of the 52 oligomenorrhoeic girls and only one of four girls with secondary amenorrhoea had a hypogonadotrophic endocrine pattern. The present study and available literature support the view that oligomenorrhoea in adolescents is not a stage in the physiological maturation of the hypothalamic pituitary-ovarian axis but an early sign of PCOS associated with subfertility. Physicians should consider endocrine evaluation before reassuring oligomenorrhoeic girls or prescribing oral contraceptives to these girls.     

DHEAS和SHBG联检在PCOS中的应用

目的：探讨多囊卵巢综合征（PCOS）患者血清硫酸脱氢表雄酮（DHEAS）与性激素结合球蛋白（SHBG）的变化。方法：检测了373例PCOS患者血清DHEAS、SHBG、FSH、LH。结果：PCOS患者血清DHEAS水平明显较对照组高（P〈0.05）,其DHEAS与SHBG浓度呈负相关关系（P〈0.05）,LH与FSH的比值升高。结论：DHEAS和SHBG联合检测在PCOS的诊断中具有一定的指导意义。     

Leptin concentrations in hirsute women with polycystic ovary syndrome or idiopathic hirsutism: influence on LH and relationship with hormonal, metabolic, and anthropometric measurements.

BACKGROUND: The known association between leptin, obesity and insulin action suggests that leptin may have a role in polycystic ovarian syndrome (PCOS) but this has only been addressed peripherally. METHODS: We assessed the influence of leptin on LH and investigated the relationship between leptin and body mass index (BMI), waist:hip ratio (WHR), androgen concentrations, fasting insulin and insulin:glucose ratio (IGR) in 27 women with PCOS and in 20 age- and weight-matched women with regular, ovulatory menstrual cycles and idiopathic hirsutism (IH). RESULTS: Leptin concentrations were significantly higher in obese PCOS women than in normal weight women with either PCOS or IH (P = 0.0028), but did not differ between obese women with PCOS and IH. WHR, insulin concentrations and IGR were significantly higher in obese PCOS patients in comparison with the three other groups. In IH patients, the association between leptin concentrations and WHR was lost after adjustment for BMI. In PCOS patients, a significant correlation was observed between leptin and fasting insulin concentrations, IGR, WHR and LH. After adjustment for BMI, only the correlation with LH remained significant. A stepwise regression model was set up with LH as the dependent variable to test the hypothesis that the concentrations of leptin might be modulating the concentrations of LH in PCOS patients. The relationship of LH concentrations with IGR was found to be BMI dependent. In contrast, leptin concentrations contributed negatively and significantly to LH concentrations, independently of either BMI or IGR. CONCLUSIONS: We speculate that the known attenuation in basal or stimulated response of LH in obese PCOS patients might be related to leptin resistance, which could influence LH hypersecretion. In IH ovulatory patients, normal LH concentrations suggest the presence of preserved regulatory mechanisms of GnRH pulsatility. Further studies are needed to specifically investigate the proposed correlation between leptin and GnRH modulation in PCOS.     

Changes in luteinizing hormone and insulin secretion in polycystic ovarian syndrome

Uncertainties regarding the pathogenetic changes underlying the polycystic ovarian syndrome (PCOS) have been reported. The aim of this study was to investigate the endocrine and metabolic features of PCOS patients in relation to luteinizing hormone (LH) secretion. Androgen assays, oral glucose tolerance tests, hyperinsulinaemic euglycaemic clamps and gonadotrophin releasing hormone (GnRH) tests were performed in 100 patients. Sixty-six patients scheduled as hyperinsulinaemic and 34 as normoinsulinaemic showed similar concentrations of LH, follicle stimulating hormone (FSH), LH/FSH ratio, and LH response to GnRH testing. Hyperinsulinaemic subjects showed higher body mass index (BMI), insulin resistance, testosterone and free androgen index levels compared with those of normoinsulinaemic subjects; when clustered in relation to their LH basal concentrations, the two groups obtained differed only in androstenedione concentrations. Considering both insulin and LH plasma concentrations, four groups were obtained. Hyperinsulinaemia and hyper-LH secretion were not related in 54% and coexisted in the same subjects in 26% of cases. Hyperinsulinaemia as well as hyper-LH secretion affected the expression of the syndrome; the insulinaemia was directly correlated with testosterone concentrations and all metabolic parameters that affected the free androgen index. The LH concentrations were related to androgen production and were independent of BMI and insulin concentrations. It is concluded that the degree of hormonal alteration is the final sum of such pathogenetic factors.     

PCOS患者不良妊娠结局的相关因素分析

目的 探讨多囊卵巢综合征(PCOS)患者不良妊娠结局的相关因素.方法 回顾性分析我院2009年1月至2017年1月收治的82例PCOS患者的临床资料及妊娠结局,根据妊娠结局分组,比较各组临床资料,且通过Logistic多因素回归分析影响PCOS患者妊娠结局的危险因素.结果 不良妊娠结局发生率15.85％;不良妊娠结局组与非不良妊娠结局组在体重指数(BMI)≥25kg/m2、腰臀比≥0.8、妊娠期糖尿病(GDM)发生率、血清卵泡刺激素(FSH)、黄体生成素(LH)、总睾酮(T)、性激素结合蛋白(SHBG)、空腹胰岛素(INS)、游离睾酮指数(FTI)上比较差异均有统计学意义(P＜0.05);Logistic多因素回归分析显示PCOS患者不良妊娠结局发生的危险因素包括BMI、腰臀比、GDM、INS、FTI,保护因子为SHBG(均P＜0.05).结论 PCOS不良妊娠结局主要包括早产、流产等,其发生与患者高BMI、大腰臀比、GDM、FTI等密切相关,需根据相关因素积极纠正,以改善患者妊娠结局.     

The management of persistent menopausal symptoms with oestradiol-testosterone implants: Clinical, lipid and hormonal results

Seventeen patients attending two menopause clinics were treated with combined subcutaneous implants of oestradiol (40 mg) and testosterone (100 mg), because oral oestrogens had not provided adequate symptomatic relief, particularly of decreased libido. There were significant improvements in libido, enjoyment of sex and tiredness (P < 0.01), and in lack of concentration (P < 0.05), but there was no significant change in flushes, sweats and depression. Based on an analogue scale, libido increased from a mean basal score of 13.5 to a maximum of 86.1 at 3 mth. Symptomatic improvement was maintained for 4–6 mth.

There were no significant changes in total serum cholesterol and triglycerides nor in cholesterol subfractions. When expressed as a percentage of the preimplant values, maximal changes in hormonal parameters were observed at 1 mth. Thus, follicle stimulating hormone (FSH) was 53% of basal, luteinising hormone (LH) 54%, oestradiol 186%, total testosterone 291%, and free testosterone 342%. Only 1 patient complained of hirsutism and weight gain.

We conclude that the hormonal implants provided substantial symptomatic relief, particularly of loss of libido, while causing rises to mid-follicular concentrations of oestradiol and maximal testosterone levels about three times normal, without significant effects on plasma lipids.     

Treatment of normal women with oestradiol plus progesterone prevents the decrease of leptin concentrations induced by ovariectomy

To study the role of oestradiol and progesterone in the secretion of leptin, 21 normally ovulating women were recruited from those scheduled for ovariectomy plus hysterectomy performed in mid-follicular phase of the cycle. Seven of the women were used as controls and received no hormonal treatment post-operatively. Another seven women received oestradiol (oestradiol group) and the remaining seven women received oestradiol plus progesterone (oestradiol plus progesterone group). Serum leptin values showed a temporal but significant increase 24 h after the operation and were significantly correlated with the cortisol and progesterone values, which increased temporarily at 12 h. At that time a marked decline in oestradiol concentrations was seen. After the temporal increase, leptin values in the controls and the oestradiol group decreased significantly up to day 4 (P: < 0.05), while in the oestradiol plus progesterone group they increased (P: < 0.01) and were significantly higher than in the other two groups (P: < 0.05). Body mass index (BMI) was the most important variable accounting for the changes in leptin values post-operatively, but in the oestradiol plus progesterone group progesterone correlated significantly with leptin independently of BMI. These results suggest that progesterone and cortisol can stimulate leptin secretion in women regardless of oestradiol concentrations.     

Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity

The effects of treatment of patients with gonadotrophin-releasinghormone analogue (GnRHa) combined with purified follicle stimulatinghormone (FSH) for in-vitro fertilization (IVF) were investigatedin detail to determine the influences of different administrationroutes and the degree of suppression of luteinizing hormone(LH). Responses to exogenous gonadotrophins were studied ininfertile women (n = 60) with normal menstrual rhythm whoseendogenous gonadotrophin activity was suppressed using a GnRHain a long protocol. They were randomized to receive i.m. administrationof human menopausal gonadotrophins (HMGim, Pergonal) or purifiedfollicle stimulating hormone (FSH, Metrodin High Purity) administeredeither i.m. (MHPim) or s.c (MHPsc). Responses were assessedby measuring plasma FSH, LH, oestradiol, testosterone and progesterone.After stimulation day 4, the MHPsc group showed significantlyhigher circulating concentrations of FSH than either the MHPimor HMGim group. However, the HMG group showed significantlyhigher oestradiol concentrations after stimulation day 5 thaneither MHP group. The differences in circulating oestradiolconcentrations in the MHP-treated patients appeared to be stronglyinfluenced by the mean circulating concentrations of LH in thefollicular phase. The patients who showed mean follicular phaseLH concentrations of <1 IU/1 showed longer follicular phases,lower circulating oestradiol and testosterone concentrationsand also lower follicular fluid concentrations of oestradioland testosterone, indicating a reduction in the normal follicularmetabolism of progesterone to androgens and oestrogens underthese conditions. This group of patients also showed longerfollicular phases, which may have consequences for future clinicalmanagement.     

The effect of age on the cyclical patterns of plasma LH, FSH, oestradiol and progesterone in women with regular menstrual cycles

Luteinizing hormone (LH), follicle-stimulating hormone (FSH),oestradiol and progesterone concentrations in plasma were obtaineddaily throughout the menstrual cycles of 94 regularly cyclingwomen, aged between 24 and 50 years. Although mean LH concentrationschanged little with advancing age, mean FSH concentrations weresignificantly (P< 0.001) elevated from the age of 39 years.FSH concentrations in the oldest women studied (48–50years) were 3-fold greater than in the younger controls (womenaged 23–35 years). LH concentrations rose slightly (P< 0.05) during the last 5 years only. The increase in FSHconcentration was not, however, uniform across the cycle, butwas confined predominantly to the mid-follicular and post-ovula-toryphases (i.e. those times in the normal menstrual cycle whencirculating inhibin concentrations appear to be minimal). Despitethe clear increases in FSH concentration, there was little alterationin the mean steroid profiles which remained within the normalfertile range throughout the last decade of reproductive life.The only exception to this was a small, transient, but significant(P< 0.05) decrease in pre-ovulatory oestradiol concentrationbetween the ages of 36 and 38 years, which was followed by atransient increase (P< 0.01) in oestradiol concentrationbetween 39 and 44 years. However, no corresponding significantchanges in mean progesterone concentrations were observed.     

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones,SHBG and bone mineral density

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2–3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E₁) and 17-β-estradiol (E₂) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E₂. During the next 3 years, the levels of E₂ and E₁ showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), Δ⁴-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E₁, E₂ and T. BMI correlated positively with E₁ and E₂. The concentrations of the free fraction of E₂ and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.     

Positive feedback effect of oestradiol in superovulated women.

To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances.     

血清Leptin在2型糖尿病、肥胖发病机制中的临床价值

目的：研究2型糖尿病血清Leptin与胰岛素,体脂分布和睾酮的关系。方法：对65例2型糖尿病患者及42例正常对照者用放免法测定血清Leptin及胰岛素。34例糖尿病患者进行75克葡萄糖耐量试验,32例行螺旋CT SSD技术测定体脂分布。30例男性糖尿病患者测定血清睾酮。结果：在调整了BMI（体重指数）,性别后,糖尿病组与对照组血清Leptin无差异。女性血清Leptin为男性的2．3倍,餐后2小时血清Leptin较空腹下降为19．19％,代谢控制不良者（空腹血糖＞14mmol)Leptin水平较低。性别,BMI,ASF（腹部皮下脂肪）是影响血清Leptin的重要因素,Leptin浓度与体重指数,胰岛素,腹部皮下脂肪显著正相关,与睾酮负相关,结论：2型糖尿病患者无异常血清Leptin,提示Leptin并非致2型糖尿病的主要因素,代谢控制不良者有Leptin缺乏,男性较低的Leptin可能与睾酮有关,性别,体重指数,腹部皮下脂肪是影响Leptin的主要因素。