The localization of estrogen receptor alpha and its function in the ovaries of postmenopausal women

The localization of estrogen receptor alpha (ERalpha) in the ovaries of postmenopausal women is a very up-to-date topic in the aspect of using estrogens therapy in the clinical situations of different type. In ovaries of reproductive age women ERalpha is present in ovary stroma, theca and granulosa cells, ovary surface epithelium (OSE) and in corpus luteum. The ovaries of postmenopausal women are smaller than those of women at the reproductive age, the division into cortex and medulla gets blurred, the ovaries have no follicles any longer, and the stroma is mainly composed of fibrous connective tissue, corpora albicantia, nerves, and blood and lymphatic vessels. The aim of our study was to investigate the immunolocalization and immunoexpression of ERalpha in the ovaries of postmenopausal women. The study involved 50 postmenopausal women who had their ovaries removed by laparotomy due to non-neoplastic diseases of the uterus. The women were divided into 3 groups (A, B, and C) depending on the time that had passed since the last menstruation. Group A consisted of women who had their last menstruation no more than 5 years earlier, in group B menopause occurred 5 to 10 years earlier, group C was composed of patients who had the last menstruation over 10 years earlier. In all the patients concentrations of follicle stimulating hormone (FSH), luteinizing stimulating hormone (LH), estradiol (E2), testosterone (T), androstendione (A) and dehydroepiandrosterone sulphate (DHEAS) in blood plasma were measured. Ovarian tissue was obtained during surgery. For morphological studies, ovaries were fixed in Bouin;s solution and 4% formalin and embedded in paraffin. Morphological analysis was carried out after hematoxylin-eosin (HE) staining. Comparing to groups A and B, the ovaries in group C contained a small number of corpora albicantia located in the medullary part as well as thinned blood vessels and few lymphatic vessels and nerves. For immunoohistochemical expression of ERalpha paraffin-embedded specimens fixed in 4% buffered formalin were used. The sections were next incubated with monoclonal mouse anti-human ERalpha antibody (N 1575 Dako, Denmark). Immunohistochemical nuclear expression of ERalpha in OSE, in epithelial inclusion cysts, in stroma, and in group A also cytoplasmic expression of ERalpha in luteal and paraluteal cells of disappearing corpus luteum were revealed. Immunohistochemical expression of ERalpha seems to decrease in the ovaries of women after menopause.     

Analysis of pituitary gonadotropin concentration in blood serum and immunolocalization and immunoexpression of follicle stimulating hormone and luteinising hormone receptors in ovaries of postmenopausal women

The participation of gonadotropins in ovarian carcinogenesis is well known and is supported by studies with inhibition of pituitary gonadotropin secretion, which results in a diminished risk of cancer. However, there are few data on localization and expression of Follicle Stimulating Hormone and Luteinising Hormone Receptors (FSHR and LHR) in ovaries of healthy postmenopausal women, and their correlation with FSH and LH concentration in blood serum is unknown. The aim of our study was to analyze gonadotropin concentration in blood serum and the expression of FSHR and LHR in ovaries of 207 postmenopausal women. Patients included in the study were divided into three groups depending on the number of years since menopause. We analyzed the concentration of FSH and LH in blood serum and the expression of FSHR and LHR in ovaries. Ovaries of postmenopausal women showed numerous morphological changes in the cortex and medulla when compared to the structure of ovaries of women at reproductive age. In all groups of patients clefts in the surface epithelium and epithelial inclusion cysts were found. The concentration of FSH and LH in the blood serum of women studied increased significantly with time from menopause. Significant differences between analyzed menopausal groups were found. The highest FSH and LH concentration in blood serum were found in women with the longest period of time from menopause. Quantitatively similar expression of FSHR and LHR was found in ovarian surface epithelial cells, in epithelial inclusion cysts and in the connective tissue cells of ovarian stroma. The intensity of the immunohistochemical reaction decreased with time from menopause and with age.     

Osteoporosis after Oophorectomy for Non-malignant Disease in Premenopausal Women

The role of oophorectomy in the development of osteoporosis was assessed retrospectively in 258 women who had been hysterectomized premenopausally for non-malignant disease. Bone density was assessed using the radiographic density of the third metacarpal. Oophorectomy before the age of 45 years was found to be associated with a significantly increased prevalence of osteoporosis within three to six years of operation. The bone density of women oophorectomized after the age of 45 years was indistinguishable three to six years after operation from that found in healthy women with intact ovaries. These findings confirm the major part played by loss of ovarian function in the development of postmenopausal osteoporosis.     

Increased risk of atherosclerosis in women after the menopause.

An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women, but there have been few studies of the association between menopausal state and atherosclerosis. In this study 294 premenopausal and 319 postmenopausal women aged 45 to 55 were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to represent intimal atherosclerosis. Aortic atherosclerosis was present in eight (3%) of the premenopausal women and in 38 (12%) of the postmenopausal women. After adjustments for age and other indicators of cardiovascular risk women with a natural menopause had a 3.4 times greater risk of atherosclerosis than premenopausal women (95% confidence interval 1.2 to 9.7; p less than 0.05); women who had had a bilateral oophorectomy had a 5.5 times greater risk (1.9 to 15.8; p less than 0.005). No excess risk of atherosclerosis was observed among women who had had a hysterectomy without removal of both ovaries. These results suggest that when oestrogen production stops, either naturally or after surgery, the risk of atherosclerosis is increased.     

Maternal age at last birth in Egypt

To assess the effects of women's education, residence, and marital experience on their age at the birth of their last child, a proportional hazards regression model was applied to 1980 Egyptian Fertility Survey (EFS) data. The detailed data include the date of birth of each child for every women interviewed, and the woman's date of birth and age at interview. Age at last birth was examined by regression analysis on birth history and socioeconomic information. 4 hypotheses were tested: women who are well educated have a greater probability of ending childbearing earlier than women with less education; women in rural areas have a higher probability of having their last child at older ages than urban women; marital disruption without remarriage lowers the probability of older maternal age at last birth; and marital disruption with remarriage increases the probability that a woman stops reproducing at an older age. The overall chi-square indicates a significant regression. All coefficients were significant, except the coefficient for women with intact 1st marriages. Women with more education had a greater probability of ending childbearing earlier than women with less education. Rural women tended to have their last children at ages significantly older than overall age at last birth. Current residence in urban areas had the opposite effect. The coefficient for those with intact 1st marriages was insignificant, meaning that the mean age at last birth for this group of women was not much different from the overall mean. Remarried women tended to end childbearing at ages significantly older than the overall average age at last birth, suggesting that these women tended to have children by their new husbands. Those with dissolved 1st marriages who had not remarried had a higher probability of ending childbearing earlier than did older women. Marriage age and final parity had highly significant negative coefficients; as marriage age and number of children born increased, so did the "survival" time or the age at last birth. Results from the hazards model indicate that the effects were as anticipated. The median age at last birth for the total sample of women aged 45-49 was 45-49 years. The median age at last birth was about 2 years older for rural compared to urban women. Illiterate women had the oldest median age at last birth of the education groups. There was little differences between median ages at last birth for women with intact 1st marriages and those whose 1st unions were dissolved and who had remarried. The median age at last birth increased with final parity.     

Cessation of childbearing in the absence of contraception in Sri Lanka

In data from the Sri Lanka Fertility Survey, 1975, the cessation of childbearing is examined among women who have never used contraception. The sample consisted of 6810 currently or previously married women, 57% of whom reported that they had never used contraception. Cessation of childbearing is studied according to age and marriage duration. The variables analyzed are age at last birth, proportions infertile during the last 5 or 7 years, and the infertile open interval. The duration of breastfeeding is taken into account where necessary, and the contraceptive users and nonusers are compared where appropriate. Non-users tend to cease childbearing early, and therefore are infertile for longer periods during their marriages. It is probably age of the 1st child that influences decisions on future fertility. Among women aged 45-49 who married before age 20 and continued in their 1st marriage, mean age at last live birth in non-users, was 34.5 years, about 2 years earlier than in those who had used contraception. Non-users who married at any age below 30 years cease childbearing well below age 40. The proportion not currently pregnant and infertile over the past 5 years increases with marriage duration among the fertile non-users in each age group. When age at last birth and the duration of breastfeeding in the open interval are taken into account and the reference period is increased to 7 years, the period of infertility increases with marriage duration among nonpregnant non-users below age 45. The proportion of women who were currently not pregnant and had remained infertile over the past 7 years is higher among the older non-users whose 1st child was born more than 10 years ago.     

Hormone concentrations in the homogenates of ovarian tissue and blood serum in postmenopausal women not using hormone therapy

Ovaries in postmenopausal women synthesize steroids, mostly androgens. Removal of the ovaries after menopause may be reflected by menopausal symptoms and arterial hypertension observed during postoperative period, along with a significantly increased risk of death due to cardiovascular complications. It is not understood if the clinical consequences of gonad removal at different time points after menopause are similar. The aim of this study was to evaluate ovarian steroidogenesis and consequently to define the role of the ovaries in postmenopausal women depending on the time after menopause. Concentrations of hormones were determined in ovarian homogenates and serum of postmenopausal women. This study included 207 postmenopausal women. They were divided into groups depending on the time after menopause. All participants had laparotomic removal of the ovaries. Concentrations of estradiol, testosterone and androstenedione were measured in ovarian homogenate and serum. The study revealed that ovarian homogenate and serum concentrations of estradiol, testosterone and androstenedione were the highest in women up to 5 years after menopause and since then significantly decreased. This study showed that testosterone, androstenedione and estradiol are synthesized in the postmenopausal ovaries. The peak synthesis of these hormones occurs up to 5 years after menopause and significantly decreases thereafter.     

The apoptotic actions of platelets in acute ischemic stroke

Stroke is a disease that affects the blood vessels that supply blood to the brain. Although platelets are implicated in the pathophysiology of stroke the mechanism is still not clear and there antiplatelet agents available for the prevention and treatment of stroke. We herein examined the relationship between the potential cytokine, TNF-α platelet activation and apoptosis in acute ischemic stroke patients. We selected 60 patients (mean age 57.9 ± 10.2 years) who had not taken any antiplatelet drugs for 14 days. A group of 45 participants (mean age 51.05 ± 9.07 years) were selected as the control group. For both the patients and for the control group, P-selectin (CD62p) and Annexin-V binding, cytochrome-c levels, caspase-3 gene expression and caspase-3 releasing and plasma TNF-α levels were measured in platelets. The results showed significant increase in plasma TNF-α and platelet Annexin-V, CD62p, cytochrome-c and caspase-3 gene expression in stroke patients compared to the control group. The data of this work suggests that inflammation may have a role in platelet apoptosis in stroke which may suggest a new aspect of the role of inflammation in the development of acute ischemic stroke.     

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE--To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN--Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING--Gynaecological endocrine clinic in tertiary referral centre. PATIENTS--Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS--Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT--Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS--Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS--Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.     

Common carotid artery stiffness, cardiovascular function and lipid metabolism after menopause

While cardiovascular disease is a major cause of death in elderly women, relatively little is known regarding the influence of menopause on atherogenesis. We tried to characterize postmenopausal changes in the arterial properties. A group of 72 postmenopausal women were classified into subgroups based on duration of the postmenopausal period (PMP): Group PM1 (1-2 years; n = 16), PM4 (2-6 years; n = 16), PM8 (6-10 years; n = 25), and PM12 (10-15 years; n = 15). The control group consisted of 24 volunteers with regular menstruation (PM0). The diameter pulse waveform and intima-media thickness (IMT) of the common carotid artery (CCA) was measured using a phase-locked echo tracking system coupled with B-mode ultrasonography. The stiffness index was calculated from the waveform and the systemic blood pressure. The cardiac contractile force and the cerebral perfusion were also estimated using the maximum incremental velocity (MIV) and the calculated blood flow, as well as the fasting lipid profile. When compared to control, significant and progressive increases were noted in total cholesterol and low density lipoprotein (PM1, PM4, PM8, PM12), IMT (PM8, PM12), and SI (PM1, PM4, PM8, PM12). Further significant and progressive reductions were noted in pulse amplitude of CCA diameter (PM1, PM4, PM8, PM12) and MIV and cerebral perfusion (PM8, PM12). The postmenopausal increase in CCA stiffness as well as lipid profile occurs earlier than the increase in IMT and may be a more sensitive predictor of disorder on arterial property.     

益坤宁对围绝经期大鼠卵巢细胞凋亡率及caspase-3表达的影响

目的:研究中药益坤宁(yikunning,YKN)对围绝经期大鼠卵巢细胞凋亡率及凋亡相关基因caspase-3基因表达的影响,探讨益坤宁治疗围绝经期综合征的作用机理。方法:选用30只自然衰老的围绝经期雌性大鼠,随机分为中药益坤宁实验组、围绝经期对照组和利维爱(livial)对照组,另选10只青年雌性大鼠作为青年对照组。连续灌胃处理4周后,采用原位脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测大鼠卵巢细胞凋亡率,采用逆转录-聚合酶链反应(RT-PCR)和蛋白印迹(Western blot)检测大鼠卵巢中caspase-3 mRNA和蛋白表达。结果:益坤宁组大鼠卵巢细胞凋亡率显著低于围绝经期对照组(P0.01);益坤宁组大鼠卵巢中caspase-3 mRNA和蛋白表达低于围绝经期对照组,高于青年对照组,差异有统计学意义(P0.01)。结论:中药益坤宁通过降低围绝经期大鼠卵巢细胞凋亡率,下调卵巢中凋亡相关基因caspase-3的表达,从而延缓卵巢衰老,这可能是其治疗围绝经期综合征的分子机制之一。     

The endocrinology of the menopauseProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Menopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Ovarian primordial follicle numbers decrease with increasing age up to about age 38 following which there is a much steeper decline in the last 12 or so years of reproductive life. At the time of the menopause itself, few follicles remain within the ovary. The recent availability of assays specific for the dimeric inhibins A and B has permitted clarification of the endocrine events leading up to and occurring around the time of final menses. Those women who show clear elevations in serum FSH above age 40, while continuing to cycle regularly have significantly lower inhibin B levels than those whose FSH levels remain in the range seen earlier in reproductive life. Early in the menopause transition, when cycle irregularity is first observed, the initial event is a decline in circulating inhibin B levels in the early follicular phase. In the late perimenopause, levels of estradiol and inhibin A also fall, inhibin B levels remain low and FSH is markedly elevated. The variability of hormone levels in women in their 40s, even in those who are continuing to cycle regularly makes FSH and estradiol unreliable markers of menopausal status. Serum androgen levels appear to fall with age rather than having any clear cut relationship to the menopause transition or menopause. The endocrine changes which occur during the menopausal transition and early postmenopausal period have clinical consequences in terms of symptoms and changes in bone mass.     

Effects of age and obesity on the conversion of androstenedione to estrone in postmenopausal women

The effects of aging as well as body weight on conversion of circulating Androstendione (A) to Estrone (E1) in 21 postmenopausal women of different ages and body weights have been studied. Serum concentration of A and E1 were measured by RIA. The E1/A ratio was correlated with total body weight, body mass index, excessive body weight, age and years after cessation of menstruation. The results show that the E1/A ratio was significantly correlated with total body weight, body mass index and excessive body weight. In contrast the E1/A ratio is not significantly correlated with age or years after cessation of menstruation.     

Accelerated vertebral bone loss in relation to the menopause: a cross-sectional study on lumbar bone density in 286 women of 46 to 55 years of age

Bone mineral density (BMD) of the lumbar spine was measured in 286 women (46–55 years of age) using dual photon absorptiometry. The women were classified in three categories: premenopausal, perimenopausal and postmenopausal. The postmenopausal group was subdivided according to the number of years since the last uterine bleeding. with multiple linear regression analysis of lumbar BMD on age and menopausal status, an acceleration of bone loss was observed during the perimenopausal period and the following first two postmenopausal years. No significant bone loss was detected in relation to age or during the later postmenopausal years. Applying both an additive and a multiplicative model of bone loss, the mean perimenopausal bone loss was 0.061 gramequivalents hydroxyapatite (geqHA)/cm² and 6.4%, respectively. In the first 2 postmenopausal years the mean bone loss was 0.044 geqHA/cm² and 5.1% per year. These results suggest a substantial menopause related acceleration of lumbar bone loss in a relatively short time span with its onset in the perimenopausal period.     

Different involutionary changes in bone mineral density with age in three skeletal sites in healthy Polish women

The aim of the study was to estimate the differences in bone mineral density (BMD) at three skeletal sites, with regard to age and menopausal status.The study was conducted between 2001 and 2006 in the Polish city of Wroc?aw and the sample was comprised of 440 healthy female inhabitants aged 40–88 years. The measurements of bone mineral density were taken at three sites: femoral neck, Ward's triangle and trochanter major. Two bone mineral density characteristics were used in further analysis: absolute measure of bone mineral density (BMD) expressed in g/(100 mm)², and % of BMD of the peak value calculated for young adults (20–45, USA reference population). Pre- and postmenopausal status was defined according to occurrence of menstruation within the last 60 days.The changes in bone mineral density with age showed significantly different patterns in different skeletal sites. While the decrease in bone mineral density in the femoral neck and Ward's triangle were parallel and gradual, the changes in trochanter major were very small and between the age groups 51–55 and 71–75, nearly unnoticeable. A comparison between pre- and postmenopausal women aged 46–55, showed a significant effect of menopausal status. The average bone mineral densities in the three skeletal sites were higher in premenopausal than in postmenopausal women. The highest value of bone mineral density was found in the femoral neck, significantly lower in Ward's triangle, and a little lower (non-significantly) in the trochanter major than in the Ward's triangle. Postmenopausal women had a little higher BMD value in the trochanter major than in the Ward's triangle site.     

Sex hormones and skin collagen content in postmenopausal women.

Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.     

Evaluation of the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing

To evaluate the relative rates of bone mineral content loss in postmenopause due to both estrogen deficiency and ageing, three groups of women were studied by computerized bone densitometry at the radius mid-point and at the distal point, modified according to the Abwrey technique. All women were in apparent good health and never had estrogen therapy. In the first group there were 64 women aged between 30 and 50 who were ovariectomized between 25 and 35 years of age. The second group was made up of 309 women between 50 and 55 years. In the third group there were 136 women aged 30-50 with normal ovaric function. The ordinary functions of linear polynomial regression were used to describe the variations in density with age. The percentage of postmenopausal bone loss was determined by calculating the BMC value at the start of the menopause and again twenty years later, according to the linear regression equation of postmenopausal period of each group of women in the study. The women who had natural menopause showed an average bone loss per year of 1.63% at the mid radius and 1.0% at the distal point. The ovariectomized women had an average loss of 0.85% at the mid point and 0.66% at the distal point. No significant decrease of bone mass was found before menopause. From a comparison between the two groups of women with analogous periods of menopause, it comes out that, during the first 20 years of natural menopause, estrogen deficiency is responsible for 52.5%-66.4% of the bone mineral loss, the remaining amount being attributable to other causes, connected with ageing. Estrogen deficiency is therefore, the principal factor causing bone mineral loss in natural menopause.     

Osteoporosis of Lumbar Vertebrae and Calcification of Abdominal Aorta in Women Living in Durban

To try to establish whether mechanical stress and muscular activity in earlier life influence the incidence and severity of spinal osteoporosis in old age lateral x-ray films of the lumbar vertebrae were obtained from three matched groups, each of 100 women 50 to 90 years old. Group A was of rural Bantu accustomed to carrying heavy loads on their heads. Group B was of urban Bantu, mainly in domestic service. Group C was of women of European origin.Severe osteoporosis occurred in three cases from group A, two from group B, and 14 from group C. Lesser degrees of osteoporosis could not be assessed precisely enough for inclusion in these figures. Evenly biconcave vertebral bodies, strongly suggestive of osteomalacia, were seen in 10 from group A, five from group B, and one from group C. In many Bantu subjects the fifth lumbar vertebra appeared flattened though of good radiodensity and with no marked changes in the other vertebrae. Twenty-eight of these were from group A, 16 from group B, and none from group C.About a third of each group showed severe degenerative changes in the spine; another third showed milder changes. More cases of spondylolisthesis occurred in the Bantu groups than in the white group. Severe calcification in the abdominal aorta was noted in 24 women in group C. Mild signs occurred in 35 further women from group C, in six from group B, and in only one from group A.     

The effect of initiation of child supplementation on resumption of post-partum menstruation

The effects of initiation of solid and liquid supplementation on resumption of post-partum menstruation are examined, using data from a 2-year prospective study of birth interval dynamics from central Java, Indonesia. The sample analysed consisted of 444 women who experienced resumption of menses while breast-feeding, women who were breast-feeding and amenorrhoeic at the end of the study, or women who resumed menstruation or were censored after infant mortality and weaning which preceded the resumption of menses. Multivariate hazard model analysis was used to assess the significance of supplementation, various breast-feeding covariates, and age and parity of the dependent variable. Because the timing of supplementation varies, the supplementation variables were introduced into the analysis as time-varying covariates. For the mothers in the sample, solid and liquid supplementation was initiated at medians of 2.1 and 8.0 months respectively. The former had a significant effect on resumption of menses, while the latter was only marginally significant. Earlier supplementation meant shorter durations of amenorrhoea for the majority of women. However, the effect was not consistent across all categories of women. For the small group of mothers who were low intensity breast-feeders (less than or equal to 6 minutes per nursing episode) or as low frequency day-time breast-feeders (less than or equal to 6 nursing episodes per day-time), earlier supplementation had no additional effect on their rate of resumption of menses post-partum.     

17beta-estradiol regulation of human growth hormone (hGH), insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) axis in hypoestrogenic, hypergonadotropic women

OBJECTIVE: Ovarian hormonal function may be as important contributing factor to hGH-IGF-I-IGFBP-3 axis as age. AIM: To examine plasma hGH, IGF-1 and IGFBP-3 levels in women with premature ovarian failure compared to healthy normal controls and postmenopausal ones. PATIENTS: Group A-15 women with premature ovarian failure (POF) (mean: age 38.9+/-5.2 years, FSH 101.4+/-29.0 IU/l; 17beta-estradiol 22.5+/-14.6 ng/l). Group B consisted of 15 menopausal women (mean: age 54.7+/-2.7 years; FSH 81.9+/-32.1 IU/l; 17beta-estradiol 17.1+/- 8.0 ng/l). Group C - controls - 15 normally menstruating women (mean: age 37.1+/-9.0 years; FSH 6.2+/-1.0 IU/l; 17beta-estradiol 144.8+/-117.1 ng/l). METHODS: Body mass and BMI were measured. Basic fasting plasma hGH, IGF-I, IGFBP-3, insulin, testosterone and LH as well as prolactin (PRL), FSH and estradiol were assessed by RIA kits. Statistical analysis. Shapiro-Wilk test, Mann-Whitney u-test, Spearman rang correlation coefficient, stepwise multiple regression. RESULTS: Mean serum IGF-I level was the lowest (p<0.005) in group B (172.0+/-54.6 microg/l) and the highest in group C (273.6+/-109.0 microg/l). The mean plasma IGF-I level in group A was similar (NS) (208.3+/-66.5 microg/l) to that found in group B and lower (p<0.02) compared with that in group C. The lowest (p<0.005) serum IGFBP-3 level was found in group B (3.1+/-0.7 microg/l) compared to group C (4.4+/-0.3 microg/l). The mean plasma IGFBP-3 level (3.1+/-1.0 microg/l) in group A was lower than in group C (p<0.005) but identical as in group B. No statistically significant differences between groups were observed in mean hGH levels. Women in group A and C were younger (p<0.001) than those in group B. The lowest mean estradiol level was found in groups A and B. The highest was in group C (p<0.001). Mean plasma LH and FSH levels were higher (p<0.001) in groups A and B vs group C. In group C there were links between IGF-I and age (r=-0.60; p=0.014) The IGF-I/age relation disappeared in the groups A and B (rA=-0.26; rB=0.10; NS). The same regards IGFBP-3/ age link (rA=-0.44, NS; rB=0,31;NS). Estradiol level was related to hGH levels in group C (r=-0.54; p<0.05). In none of groups hGH/IGF-1 as well as IGFBP-3/hGH relations were found. Prolactin accounted for 69% of the variance in IGF-I level in the group B (p=0.003) and for 24% in group A (NS). Testosterone accounted for 88% (p=0.004) of the variance in IGF-I level in group B and IGFBP-3 was responsible for 86% (p=0.038) of the variance in IGF-I level in group C. Again IGFBP-3 was responsible for 47% (p=0.023) in group A and for 49% (p=0.04) in group B of the hGH variance. CONCLUSIONS: 17b-estradiol may be as important contributor to insulin-like growth factor-I (IGF-I) plasma level as age in hypoestrogenic, hypogonadotropic women.