Effects of sex steroid hormones and menopause on serum leptin concentrations

Leptin is a protein secreted by adipocytes; its circulating levels are correlated to fat mass and it acts on the hypothalamic centers regulating body weight. Leptin may also play an important role in regulating reproductive function. Indeed, ob/ob mice, lacking leptin due to a genetic mutation, are obese and infertile; administration of recombinant leptin to these animals reduces body weight and restores fertility. A sexual dimorphism in serum leptin levels has also been observed, with higher concentrations in women. Studies in vitro seem to indicate that estrogens stimulate leptin secretion, while in vivo studies are extremely discordant. In humans, several studies showed increased, unmodified and decreased leptin levels after the menopause. Furthermore, hormonal replacement therapy (HRT) after the menopause was reported to result in unmodified, increased or decreased leptin levels. It is likely that the effects of postmenopausal hypoestrogenism on leptin levels are masked by the postmenopausal changes in body composition. Indeed, after menopause, there is an increase in body weight, body mass index (BMI) and fat mass with a centralization of fat distribution. Administration of HRT may stop these changes and even restore a premenopausal pattern, leading then to decreased leptin levels.     

Long-term effects of the menopause and sex hormones on skin thickness

Skin collagen content and skin thickness in a group of postmenopausal women who had been treated with sex hormone implants were compared with those in an untreated group of similar women. Both skin collagen content and thickness were found to be significantly greater in the treated than in the untreated group. In the untreated women skin collagen content declined in relation to menopausal age but not to chronological age. No correlation was found with menopausal age, chronological age or duration of therapy in the treated group. These data suggest that skin collagen is influenced by the sex hormone status and declines after the menopause, contributing to the increase in urinary hydroxyproline excretion that has been reported to occur at this time.     

Long-term effects of the menopause and sex hormones on skin thickness

Summary. Skin collagen content and skin thickness in a group of postmenopausal women who had been treated with sex hormone implants were compared with those in an untreated group of similar women. Both skin collagen content and thickness were found to be significantly greater in the treated than in the untreated group. In the untreated women skin collagen content declined in relation to menopausal age but not to chronological age. No correlation was found with menopausal age, chronological age or duration of therapy in the treated group. These data suggest that skin collagen is influenced by the sex hormone status arid declines after the menopause. contributing to the increase in urinary hydroxyproline excretion that has been reported to occur a t this time.     

Effects of sex steroid hormones and menopause on serum leptin concentrations.

Leptin is a protein secreted by adipocytes; its circulating levels are correlated to fat mass and it acts on the hypothalamic centers regulating body weight. Leptin may also play an important role in regulating reproductive function. Indeed, ob/ob mice, lacking leptin due to a genetic mutation, are obese and infertile; administration of recombinant leptin to these animals reduces body weight and restores fertility. A sexual dimorphism in serum leptin levels has also been observed, with higher concentrations in women. Studies in vitro seem to indicate that estrogens stimulate leptin secretion, while in vivo studies are extremely discordant. In humans, several studies showed increased, unmodified and decreased leptin levels after the menopause. Furthermore, hormonal replacement therapy (HRT) after the menopause was reported to result in unmodified, increased or decreased leptin levels. It is likely that the effects of postmenopausal hypoestrogenism on leptin levels are masked by the postmenopausal changes in body composition. Indeed, after menopause, there is an increase in body weight, body mass index (BMI) and fat mass with a centralization of fat distribution. Administration of HRT may stop these changes and even restore a premenopausal pattern, leading then to decreased leptin levels.     

绝经过渡期妇女性激素与胰岛素敏感性的改变

目的:观察中老年妇女性激素和胰岛素敏感性与月经状态的关系。方法:年龄40~70岁妇女166例,分为5组:月经规律组、绝经过渡期早期组、绝经过渡期晚期组、绝经早期组和绝经中晚期组。分别测定雌二醇(E2)、雌酮(E1)、促卵泡激素(FSH)、睾酮(T)、性激素结合球蛋白(SHBG)、空腹血糖(FBG)、空腹胰岛素(INS),并计算游离睾酮(FT)及胰岛素作用指数(IAI)。结果:(1)T和FT在绝经过渡期早期组较其他各组有显著升高(P<0.05),在绝经中晚期组较绝经过渡期有显著降低(P<0.05)。E1/E2从绝经过渡期早期即上升,至绝经中晚期显著升高(P<0.05)。FSH从绝经过渡期早期组即显著升高。SHBG各组之间无显著性差异;(2)各组之间FBG和IAI无显著性差异。INS在绝经过渡期早期组显著升高,与绝经后比较差异有显著性(P<0.05);(3)T与E1、FBG和INS正相关,与年龄、FSH和IAI负相关,与E2不相关。结论:妇女在绝经过渡期早期,T、FT显著升高;INS显著升高,但FBG和IAI没有明显变化。     

Reproductive hormones and the menopause transition

The hormonal correlates of reproductive aging and the menopause transition reflect an initial loss of the follicle cohort, while a responsive ovary remains, and an eventual complete loss of follicle response, with persistent hypergonadotropic amenorrhea. The physiology of the process is described, along with key findings of relevant studies, with an emphasis on the Study of Women's Health Across the Nation. A clinical framework is provided to help clinicians to forecast the major milestones of the menopausal transition and to predict potential symptoms or disease.     

Effect of oestrogen and progestagen on gonadotrophins and sex hormones in oophorectomized women

Five premenopausal women were followed with measurements of androgens, oestrogens, gonadotrophins and sex hormone binding globulin (SHBG) after ovariectomy for benign disease. After a period of 6 weeks without treatment the women were treated with oestradiol 4 mg daily for 8 weeks, oestradiol 4 mg plus norethisterone acetate (NETA) 2 mg daily for 8 weeks and finally oestradiol 4 mg daily for another 8 weeks. The levels of androgens did not change during the various periods. As usual during oral treatment oestrone and oestrone sulphate were elevated while oestradiol levels were in the pre-operative range during treatment, regardless of the addition of NETA. SHBG was elevated during oestrogen-only treatment, while addition of NETA normalized the concentration of SHBG. In the combined NETA period concentrations of free oestradiol and non-SHBG-bound oestradiol were significantly elevated, and gonadotrophins returned to premenopausal levels, in contrast to the high levels in the oestrogen-only periods. Using oral oestrogen therapy it may be preferable to add a progestagen rather than elevate the oestrogen dose. Progestagen will result in more free oestradiol and give greater relief of symptoms, but the potentially harmful effect of progestagens on blood lipids must be considered.     

Exogenous sex hormones and thrombophilia

Worldwide, hundreds of millions of women use exogenous estrogens in contraceptives or for postmenopausal hormone replacement. Exogenous estrogens increase the risk for venous and arterial thrombosis. This article reviews the use of exogenous sex hormones in women with thrombophilia.     

Effect of menstrual cycle variation in female sex hormones on cellular immunity and regulation

Ovarian steroid hormones reduce cell-mediated immunity (CMI), perhaps by increasing regulatory T cells. We examined the relationship of estrogen and progesterone plasma concentrations during the menstrual cycle with circulating regulatory T cells (Treg cells) and with varicella-zoster virus (VZV)-specific lymphocyte proliferation (VZV-LPA). Twenty healthy and 20 HIV-infected women were tested at 1-4, 10-14, and 20-24days of the menstrual cycle. HIV-infected women experienced significant increases in the frequency of peripheral blood CD4+IL10+ and CD8+FoxP3+ Treg cells from the early and late follicular phases to the luteal phase of their cycles. Healthy women experienced significant increases only in CD4+IL10+ Treg cells. The increase in CD4+IL10+ Treg cells between the late follicular and the luteal phases of HIV-infected and uninfected women significantly correlated with the corresponding increases in progesterone plasma concentrations. VZV-LPA results decreased from the early and late follicular phases to the luteal phase in both groups. The decrease in VZV-LPA results significantly correlated with the increase in CD4+IL10+ Treg cells underscoring the potential immunosuppressive effect of the progesterone-stimulated Treg cells. In conclusion, the increase in progesterone levels during the menstrual cycle was associated with higher Treg frequencies and lower CMI.     

Effects of estrogenic hormones on blood lipids]

The authors have followed the effects of application of the deposit estradiolbenzoat on the blood lipides level of women at the beginning of menopause and women with arteriosclerosis. They have registered a moderate drop of the concentration of cholesterol, beta-lipoproteins, and slight changes of the non-esterified fatty acids level. Women using contraceptive hormonal mixtures were found with higher level of cholesterol in the blood serum than those being watched. The application of a single dose of androgen did not have any substantial effects on the blood lipides level.     

Changes in plasma 2-hydroxyestrone levels in pubertal females and correlation with sex hormones

Plasma levels of 2-hydroxyestrone (2-OHE1) were measured by specific radioimmunoassay during puberty to elucidate the physiological role of this hormone on female sexual development. Plasma levels of FSH, LH, PRL and estradiol (E2) were also measured with an RI-kit. 67 girls between aged 6 and 16 were selected for this study. Blood samples were collected into tubes containing 0.1W/V% EDTA and 0.1W/V% ascorbic acid and immediately centrifuged. 2-OHE1 in plasma was extracted and separated with a Sephadex LH-20 column. RIA was applied using anti 2-OHE1-17-CMO-BSA. Plasma 2-OHE1 levels before menarche were low (6-7 pg/ml) until 10 years of age. The levels started to increase from 11 and reached 11.2 +/- 5.8pg/ml at 16 years of age. The levels of 2-OHE1 in girls after menarche were significantly higher than that before menarche (p less than 0.01). There was a significant correlation between 2-OHE1 and E2 in girls before menarche (p less than 0.001, r = 0.5416). However, the 2-OHE1 to E2 ratio decreased significantly from 9 to 10 years of age. These results indicate that during this period, the E2 increase is more predominant than that of 2-OHE1. There was a significant negative correlation between 2-OHE1 and PRL after menarche while no correlation between 2-OHE1 and FSH, LH was noticed. These results suggested that 2-OHE1 may play a role in sexual development after menarche rather than in the initiation of menarche.     

Anti-fertility activities of sex hormones

The antifertility action of various sex hormones is discussed. 20 years ago it was determined that Norethynodrel and Norethindrone, newly synthesized progestins, were effective oral contraceptives in women, and that their action was attributed to inhibition of ovulation. The author, skeptical of their effectiveness and mode of action, began to study some non-steroidal compounds claimed to prevent pregnancy in laboratory animals when administered orally soon after mating. When these antiestrogens, Norethynodrel, H241, and other estrogenic compounds were subjected to tests in laboratory animals, it was found that all these compounds, with varying degree of potency, caused a rapid egg transport to the uterus and expulsion of eggs from the uterus, but that ethinyl estradiol was the most effective one in this respect. It was determined through a number of experiments that the mechanism of action of estrogen administered soon after mating can be attributed not only to the early arrival of eggs from the tube into the uterus before they are able to survive in the uterus, but also to the expulsion of eggs from the uterus. When progestins are administered before ovulation, the transportation of eggs is much earlier than normal. Degeneration of eggs also occurs during such treatment. Based on the fact that degeneration of eggs occurred when eggs at 1 stage of development were transferred into the uterus of an advanced stage as demonstrated in many species by numerous workers, the degeneration of eggs in progestin-treated animals can be expected. It is concluded that the effectiveness of steroidal oral contraceptives is due to their attack on several processes of reproduction: they not only inhibit ovulation, but can inhibit fertilization and also cause the degeneration of eggs. It is hoped that through further research, in the future new ways will be found to regulate fertility without hazardous side effects.