Objective The purpose of this study was to evaluate whether 17-α-hydroxyprogesterone caproate (17P) treatment affect changes in cervical length. Study Design Women with singleton pregnancy, between ...25 and 33 + 6 weeks of gestation, who were hospitalized for preterm labor were included. Patients with rupture of membranes and/or signs of chorioamnionitis were excluded. Sixty undelivered patients were allocated randomly to either observation or to receive 341 mg of 17P intramuscularly, twice each week until gestational week 36. Cervical length was measured by transvaginal ultrasound scanning at discharge and at day 7 and 21 after discharge. Statistical comparisons were done with analysis of variance and chi-square test. Results Shortening of the cervix in the observation group (30 cases) was higher than in the 17P group (30 cases) both at day 7 (2.37 ± 2.0 mm vs 0.83 ± 1.74 mm; P = .002) and day 21 (4.60 ± 2.73 mm vs 2.40 ± 2.46 mm; P = .002). Treatment with 17P was associated with both a reduction in the risk of cervical shortening of ≥4 mm (odds ratio, 0.18; 95% CI, 0.04-0.66) and in the risk of preterm delivery (odds ratio, 0.15; 95% CI, 0.04-0.58). Conclusion Undelivered patients after preterm labor undergo progressive shortening of the cervix, which is attenuated by 17P treatment.
Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both ...fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. Methods This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17β-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. Results and Discussion Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased.
Objective: To prospectively evaluate follicular fluid levels of vascular endothelial growth factor in women undergoing IVF cycles and to investigate the correlation of these levels with ovarian ...response to gonadotropins and with uterine or ovarian Doppler findings.
Design: Prospective study.
Setting: University hospital.
Patient(s): 41 patients undergoing ART were divided into two groups according to response to ovarian stimulation protocols: poor responders (n = 18) and normoresponders (n = 23).
Intervention(s): Doppler analysis of perifollicular arteries and assay of follicular fluid vascular endothelial growth factor.
Main Outcome Measure(s): During ovarian stimulation, patients underwent hormonal (E2), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluation. Serum and follicular fluid concentrations of vascular endothelial growth factor were assayed in each female patient.
Result(s): Compared with poor responders, more oocytes were collected and more embryos were transferred but follicular fluid levels of vascular endothelial growth factor levels were lower in normoresponders. Follicular fluid levels of vascular endothelial growth factor were inversely correlated with number of oocytes retrieved. Poor responders had significantly higher uterine and perifollicular Doppler flow resistances. The pregnancy rate per cycle was significantly higher in normoresponders (26%) than poor responders (6%).
Conclusion(s): Elevated follicular fluid levels of vascular endothelial growth factor concentrations are associated with poor ovarian response and a very low pregnancy rate.
In 15 postmenopausal women with no cardiovascular risk factors, hormone replacement with transdermal estradiol (50 microg/day for 2 months) did not enhance flow-mediated endothelium-dependent ...vasodilation, reduce endothelium-independent vasodilation, and did not modify the pulsatility index and blood flow of the brachial artery. The present data do not support a positive effect of replacement with transdermal estradiol on vessel vasodilation in healthy, postmenopausal women.
To evaluate the influence of two medical treatments for endometriosis on insulin sensitivity.
After surgery, 26 women with endometriosis were randomly allocated to a 6-month treatment with a GnRH ...agonist (Leuprorelin 3.75 mg/28 days) or a subdermal progestin implant (etonogestrel 68 mg). Insulin sensitivity (SI) and glucose utilization independent of insulin (Sg) were investigated at baseline and after 6 months by a frequently sampled intravenous glucose tolerance test (FSIGT) associated with the minimal model method.
Both therapies tended to decrease SI, but the effect did not reach statistical significance in the GnRH agonist group (5.43±1.29 vs. 3.99±0.8) and was significant in the etonogestrel group (5.74±1.12 vs. 3.95±0,78; p=.046). Sg, fasting glucose, insulin, C-peptide and C-peptide/insulin were not modified by either treatment.
The modifications of glucose-insulin metabolism induced by the GnRH agonist are of no relevance for the short-term use of this molecule. Even if the modification induced by the etonogestrel implant is subtle and of no major impact, it should be taken into consideration for the long-term treatment of individuals with abnormalities of glucose-insulin metabolism.
Objective
To compare the uterine effects of 60 mg of raloxifene with a continuous combined hormone replacement therapy, a preparation of 2 mg 17β‐oestradiol (E2) and 1 mg norethisterone acetate for a ...duration of 12 months.
Design
A randomised, double‐blind trial.
Setting
Multicentre: Europe, Israel, South Africa.
Population
Asymptomatic postmenopausal women with risk factors for osteoporosis or cardiovascular disease who had an endometrial thickness of less than 5 mm. One thousand and eight women were randomised for the six month core; of these 420 were invited to continue into a six month extension period.
Methods
Randomisation to either raloxifene or continuous combined hormone replacement therapy. Patients, recruiters and assessors were blinded to the treatment used.
Main outcome measures
The frequency of vaginal spotting/bleeding as recorded in a diary, endometrial thickness and uterine volume as measured by transvaginal ultrasonography at baseline and after 6 and 12 months.
Results
After six months of therapy with raloxifene, the rate of women on raloxifene reporting vaginal bleeding and spotting (6.8%) was similar to the rate in the lead‐in phase (8.3%) but increased from 7.0% to 55.1% in the continuous combined hormone replacement therapy group. Raloxifene treatment was not associated with a significant change from baseline to endpoint in mean endometrial thickness (P= 0.11), whereas continuous combined hormone replacement therapy treatment was associated with an increase in this value of mean (SD) of 1.2 (2.2) mm (P < 0.001). Compared with raloxifene, mean endometrial thickness for women on continuous combined hormone replacement therapy was significantly increased at endpoint 4.6 (2.1) mm vs 3.5 (1.7) mm; change from baseline P < 0.001. In the raloxifene group, there was a trend towards a decrease from baseline in uterine volume from 31.4 (20.3) to 30.3 (16.2) mm; P= 0.37; in the continuous combined hormone replacement therapy group, there was a significant increase in uterine volume from 31.3 (16.3) to 54.0 (36.1) mm; P < 0.001, and the difference in the effect of both compounds on change in uterine volume at endpoint reached statistical significance (P < 0.001). Statistically significant differences between the treatment groups were sustained for all parameters during the extension period. Early discontinuation rates, both overall and due to adverse events, were significantly lower (P < 0.001) in the raloxifene group after 6 and 12 months.
Conclusion
Compared with continuous combined hormone replacement therapy, 6 and 12 months of raloxifene treatment do not lead to vaginal bleeding/spotting, are not associated with increased endometrial thickness or uterine volume and result in a significantly lower rate of early treatment discontinuations in asymptomatic women receiving treatment to prevent long term postmenopausal health risks.
OBJECTIVE
In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, ...the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement.
DESIGN
Prior to and after 2 months of transdermal oestradiol (50 μg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double‐blind fashion.
PATIENTS
Fourteen healthy postmenopausal women.
MEASUREMENTS
Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test).
RESULTS
Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day‐placebo day) in the norepinephrine response to the cold (r 2 = 0.457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day.
CONCLUSIONS
Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.
There is much evidence indicating that the human placenta plays a very important role in modulating the endocrinology of pregnancy. Placental tissue produces cytokines, hormones and growth factors ...that are essential in the regulation of the feto-maternal unit. The production of these substances is regulated by a network of interactions within and between intra-uterine through paracrine and/or autocrine mechanisms. Communication between the gestational intra-uterine tissues is critical for successful pregnancy, from the earliest stage of implantation until the expulsive phase of delivery. This is confirmed by the demonstration that the human placenta directly controls the release of substances such as hCG, hPL, steroid hormones and prostoglandins. Furthermore, there is evidence that intra-uterine tissues also can regulate ACTH release and have effects on the hypothalamus–pituitary–gonadal axis and the hypothalamus–pituitary–adrenal axis. The set of data reported in this article confirms that the placenta must be considered an organ that is essential for the initiation, maintenance and successful conclusion of pregnancy and that an imbalance between the complex network of placental regulating systems may cause serious gestational disorders.
Because endogenous opioids have been considered to be deeply involved as a causal factor of hypothalamic amenorrhoea, this study was designed to evaluate the efficacy of the administration of ...naltrexone, an antagonist of opioid receptors, on luteinizing hormone (LH) secretion in patients with hypothalamic amenorrhoea. A total of 30 patients with hypothalamic amenorrhoea were studied. Patients were divided into two groups: group A, hypogonadotrophic (n = 15), and group B, normogonadotrophic (n = 15). All patients were administered naltrexone at a dose of 50 mg/ day per os for 6 months. A third group of 10 amenorrhoeic patients was treated with placebo per os with the same schedule. All patients were evaluated for LH spontaneous pulsatile release in baseline conditions and after 3 and 6 months of treatment. Plasma gonadal steroid concentrations increased significantly in all patients after 3 months of naltrexone therapy, but only hypogonadotrophic patients showed a sharp increase in both LH plasma concentrations and LH pulse amplitude within the first 3 months of treatment which remained unchanged until the sixth month of treatment. Plasma follicle stimulating hormone concentrations did not change significantly in any patient. Menstrual bleeding occurred within 90 days of the beginning of treatment in 24 out of the 30 patients. Patients treated with placebo did not show a significant change in gonadotrophin and gonadal steroid plasma concentrations. The results of our study support the efficacy of naltrexone administration on neuroendocrine pathways controlling LH secretion in patients with hypothalamic amenorrhoea.
Progesterone is a potent hormone acting on the female reproductive tract and influencing a series of other functions. Recent studies revealed a correlation between progesterone and brain ...neurotransmitters and neuropeptides. Our study evaluated the possible effect of norgestimate, a new progestin, on hypothalamic and pituitary beta-endorphin (B-EP) concentration in castrated female rats. Ovariectomy was performed under ethyl ether anesthesia. Treatment was started 3 weeks after surgery. Norgestimate, estradiol benzoate or norgestimate plus estradiol benzoate were administered. The two steroids were dissolved in sesame oil and injected (s.c.) every day for 2 weeks. Pituitary and hypothalamus B-EP concentrations were measured by radioimmunoassay. Our studies showed that norgestimate increases the pituitary and hypothalamic B-EP concentration in female rats, reaching values higher than controls and estrogen-treated rats. Because B-EP has an important role in reproductive function, both modulating gonadotropin secretion and sexual behavior, the present results lead to the hypothesis that norgestimate affecting B-EP concentrations may influence central functions.
