Leptin and adiponectin in the female life course

Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

Women with primary ovarian insufficiency have lower bone mineral density

The aim of the present study was to assess the prevalence of osteoporosis in a sample of 32 patients with spontaneous primary ovarian insufficiency (POI) in comparison to reference groups of 25 pre- and 55 postmenopausal women. Hip (lumbar) and spinal bone mineral density (BMD) measurements were performed by dual-energy X-ray absorptiometry in the three groups. The median age of POI patients at the time of diagnosis was 35 years (interquartile range: 27-37 years). The mean ± SD age of postmenopausal reference women (52.16 ± 3.65 years) was higher than that of POI (46.28 ± 10.38 years) and premenopausal women (43.96 ± 7.08; P = 0.001) at the time of BMD measurement. Twenty-seven (84.4 percent) POI women were receiving hormone replacement therapy (HRT) at the time of the study. In the postmenopausal reference group, 30.4 percent were current users of HRT. Lumbar BMD was significantly lower in the POI group (1.050 ± 0.17 g/cm²) compared to the age-matched premenopausal reference group (1.136 ± 0.12 g/cm²; P = 0.040). Moreover, 22 (68.7 percent) POI women had low bone density (osteopenia/osteoporosis by World Health Organization criteria) versus 47.3 percent of the postmenopausal reference group (P = 0.042). In conclusion, the present data indicate that BMD is significantly lower in patients with POI than in age-matched premenopausal women. Also, the prevalence of osteopenia/osteoporosis is higher in POI women than in women after natural menopause. Early medical interventions are necessary to ensure that women with POI will maintain their bonemass.

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals

The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5alpha-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein ß2-microglobulin as an internal control. The results are expressed as arbitrary units in relation to ß2-microglobulin absorbance (mean ± SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78 ± 0.05 vs 0.74 ± 0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85 ± 0.04) and of women with polycystic ovary syndrome (0.78 ± 0.05) and idiopathic hirsutism (0.80 ± 0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5alpha-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases

Percutaneous 17 beta-estradiol replacement therapy in hypertensive postmenopausal women

The present study evaluated the short-term effects of percutaneous 17Beta-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17Beta-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administation. Systolic and diastolic blood pressure or heart rat did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued). Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins) also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 + 27.21 to 35.09 + 20.44 IU/I, P<0.05), and an increase in estradiol levels (15.06 + 8.76 to 78.7 + 44.6 pg/ml, P<0.05). There was no effect on LH (18.0 + 9.5 to 14.05 + 8.28 IU/I). Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17Beta-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women.

Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradioltreated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 mug rat-1 week-l) for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-l) was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 mug estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 mug estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05). Therefore, the increase in serum prolactin levels observed in rats treated with 50 mug estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 mug estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats.

Effects of norethisterone acetate and tamoxifen on serum prolactin levels, uterine growth and on the presence of uterine immunoreactive prolactin in estradiol-treated ovariectomized rats

The aim of the present work was to study the effects of the antiestrogen tamoxifen 9TAM) of progestin noresthisterone acetite (NA) and of their combination on serum prolactin levels, uterine growth and the presence of uterine immunoreactive prolactin estradiol- treated rats. Ovariectomized female Wistar rats were injected sc with estradiol valerate (VE, 50 µg/rat per week) or oil vehicle. During the secon week, estradiol-treated rats also received NA (0.12 or 1.0 mg/eat, sc, daily) or TAM (0.06 mg/rat) alone or in combination with NA (0.12mg). Serum prolactin levels were suppressed to the same extent in the TAM- and 1.0 mg NA-treated groups compared with rats given estrogen alone (2.3 ñ 0.3 and 5.6 ñ 1.5 ng/ml for TAM and NA groups vs 39.7 ñ 3.6 ng/ml for VE groups, P < 0.05). Except for the lowes dose of NA, uterine wet weight and DNA content were significant reduced in all groups compared to estradiol alone (236.8 ñ 18.0 and 295.6 ñ 27.8 mg vs 309.4 ñ 32.2 mg for uterine weight in TAM and NA groups vs VE, respectively, P 0.05; and 1.14 ñ 0.05 and 0.93 ñ 0.04 mg/uterus vs 1.33 ñ 0.06 mg/uterus for uterine DNA in TAM and NA groups vs VE groups). The combination of NA and TAM resulted in a higher degree of suppression of uterine growth than when each drug was used alone, indicating an additive antiproliferative effect of NA and TAM. Although no prolactin immunostaining was detected in the uterus of rats treated with estradiol, uterine immunoreactive prolactin was identified in those treated with NA, TAM ot both. These results suggest that an inhibitory effect on the action of estradiol can play a role in the hormonal modulation of uterine secretion

Association of ovarian volume and serum LH levels in adolescent patients with menstrual disorders and/or hirsutism

Pelvic ultrasonography was performed on 25 adolescent patients with menstrual disorders and/or hirsutism. Clinical and endocrinologic state was evaluated by history, physical examination and assays of serum LH, FSH, prolactin, testosterone and androstenedione levels in order to determine a possible association between hormonal levels and ovarian volume in the etiologic investigation of these adolescent girls. Patients aged 12 to 19 years, mean 14.92 years (menarche at 12 to 16 years; mean, 12.32 years) were divided into three groups according to ovarian size at ultrasonography: group I, N = 13, both ovaries 2-10 cm3; group II, N = 5, one of the ovaries > 10 cm3; group III, N = 7, both ovaries > 10 cm3. A strong correlation between serum LH levels and ovarian volume (r = 0.647, P < 0.0001) was observed. Moreover, when comparing the hormonal levels of all three groups, serum LH levels were significantly higher in group III (group I, 3.92 +/- 3.49; group II, 5.25 +/- 2.71; group III, 9.77 +/- 3.11 mIU/ml; mean +/- SD, P < 0.003) while testosterone and androstenedione levels showed a tendency to also be higher, but this difference was not significant. This hormonal pattern is suggestive of polycystic ovary syndrome (PCOS). The present results suggest that ovarian size of more than 10 cm3 at pelvic ultrasound in adolescent girls with menstrual disorders and/or hirsutism might be predictive of PCOS and emphasize the importance of careful assessment of ovarian volume by ultrasound

Serum LH levels in the differential diagnosis of hirsute anovulatory women

Polycystic ovarian syndrome (PCO) occurs frequently in hirsute patients. A dissociated explosive response of LH to LHRH administration has been associated with the diagnosis of PCO. Twenty-four of 58 women seen because of hirsutism were found to have ovarian dysfunction based on clinical signs such as anovulation and irregular menstrual cycles. Plasma androgen levels were elevated in the patient group. The LHRH test (200 micrograms, iv) was applied to the 24 patients and compared with 13 normal ovulatory controls. Serum FSH levels before and after the LHRH test were normal in all patients. Two patterns of LH response to LHRH stimulation were observed: an explosive response in 17 patients (delta LH: 39.4 +/- 21.8 IU/l, control group: 7.35 +/- 4.4 IU/l, P < 0.01) and a normal response in 7 patients (delta LH: 7.53 +/- 2.41 IU/l). There was a significant correlation (r = 0.63, P < 0.05) between basal LH levels and LH response to LHRH. Sensitivity and specificity calculated for basal LH levels higher than 6.0 IU/l, considering the LHRH test as reference, were 58 per cent and 85 per cent , respectively. The positive predictive value measuring the possibility of LH higher than 6.0 IU/l to be from a patient with PCO (explosive response to LHRH) was 92 per cent . These data suggest that, in hirsute anovulatory patients, basal LH levels may be a good predictor in the diagnosis of polycystic ovarian syndrome