D. Lanzetta

Effects of dexamethasone and dexamethasone plus naltrexone on pituitary response to GnRH and TRH in normal women.

The hypothesis that glucocorticoids have a direct central inhibitory effect on the reproductive axis is sutained by the identification of glucocorticoid receptors on GnRH-secreting neurons and gonadotropic pituitary cells. It has been proposed that glucocorticoids and opioids interact centrally in the regulation of the GnRH-LH axis. The inhibitory effect of glucocorticoids may manifest not only directly through the hormone-receptor link, but also indirectly through an increase in opioid tone. The aim of this study was to evaluate the role of glucocorticoids and glucocorticoids combined with an opioid antagonist, in the regulation of basal and GnRH- and TRH-stimulated secretion of LH, FSH and Prl in 7 women with normal menstrual cycles. Blood samples were obtained every 10 min for an hour. GnRH (50 μg) and TRH (200 μg) were administered and blood sampling was continued every 15 min for 2 h (day 1). At 5 a.m. the next day, naltrexone (50 mg) was given and at 8 a.m. the GnRH-TRH test was repeated (day 2). At 5 a.m. on day 3, the patients took 2 mg oral dexamethasone and the test was repeated. At 5 a.m. on day 4, the patients took naltrexone and dexamethasone and at 8 a.m. the GnRH-TRH test was repeated. Administration of naltrexone did not cause significant changes in basal concentrations of LH and FSH and their response to GnRH. The area under the curve of the LH response to GnRH on day 3 was significantly less than on days 1, 2 and 4. Administration of naltrexone (day 2) did not cause any significant increase in basal and TRH-stimulated levels of Prl with respect to day 1. On day 3, dexamethasone caused a reduced response of Prl to TRH. Pretreatment with naltrexone (day 4) prevented this reduction. These results suggest that suppression of the response of LH to GnRH induced by dexamethasone may be partly mediated by endogenous opioids. Dexamethasone led to a reduction in the response of Prl to TRH, and naltrexone blocked this suppression. Hence the suppression of Prl and LH by dexamethasone must be partly mediated by endogenous opioids, which must therefore inhibit pituitary secretion of Prl.

Bone mineral density and biochemical markers of bone turnover in peri- and postmenopausal women.

Abstract. Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51 ± 8 years (43–62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)].Three groups of women were divided into two subgroups: those with normal and those with low BMD (<1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin.We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies.Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy.

Growth hormone secretion in premenopausal women before and after ovariectomy: effect of hormone replacement therapy.

OBJECTIVE To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in premenopausal women before and after ovariectomy and after 1 month of estrogen replacement therapy (ERT). PATIENTS Ten women 42 to 49 years of age awaiting combined hysterectomy and ovariectomy for a variety of benign gynecological conditions. INTERVENTION Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, P, and PRL. Stimulation with GH-RH was performed before and 8 to 10 days after ovariectomy, and after a month of ERT. RESULTS A significant reduction in GH response to GH-RH was observed after ovariectomy. Estrogen replacement therapy restored GH response to presurgical levels. CONCLUSIONS The results support the role of E2 in the stimulated secretion of GH and suggest that ERT increases pituitary stores of GH.

Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF).

Flutamide is a non‐steroid antiandrogen that specifically blocks the androgen receptor. We have investigated the effect of flutamide treatment on the adrenal androgen response to corticotrophin releasing factor (CRF) in eight patients with polycystic ovary syndrome (PCOS).

Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety

OBJECTIVE to evaluate the efficacy of combining kava extract with hormone replacement therapy in the treatment of menopausal anxiety. MATERIALS AND METHODS HAMA score was evaluated before and after therapy in four groups of women in menopause (duration of menopause ranged from 1 to 12 years). The groups were treated with hormone replacement therapy (with and without progestogens) and kava extract or placebo for 6 months. RESULTS A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. DISCUSSION The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease.

Combination of statins and hormone replacement therapy in postmenopausal women is associated with increased bone mineral density.

Recent studies have shown that statins might be potent inhibitors of bone resorption and osteoclast number ,and there is evidence for their bone anabolic effects. Statin treatment seems to protect against non-pathological fractures in older women. However ,contradictory findings have been obtained. In this retrospective study we found that postmenopausal women on statins and hormone replacement therapy (HRT) showed higher bone mineral density than women on HRT alone. This evidence provides further confirmation of the effect of statins on bone turnover and shows that the combination of HRT and statins reduces the risk of bone fracture by virtue of the antiresorptive effect of HRT and the anabolic and antiresorptive effects of statins.

Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women

The effects of 6 months of combined hormone therapy with transdermal estradiol (0.05 mg/day x 21 days) and different oral progestogens (10 mg/day medroxyprogesterone acetate [MPA] in the last 12 days, 10 mg/day dihydrogesterone in the last 12 days, and 50 mg/day cyproterone in the first 10 days), on menopausal symptoms and hypothalamo pituitary-ovarian function were studied in normal perimenopausal women. The study included 38 perimenopausal women, aged 43-49 years, with regular cycles of 26-32 days in length and menopausal symptoms. Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, and P every week until menstrual bleeding, before and during the first month of therapy. Plasma levels of LH and FSH were suppressed in the first month of therapy while E2 had a mean value of 45 +/- 12 pg/ml. Ultrasound examination and low levels of P indicated a complete block of ovulation and hypothalamo-pituitary-ovarian activity. All women reported the disappearance of vasomotor symptoms and nocturnal sweating. Transdermal estradiol and oral progestogens were well tolerated. This study shows that combined hormone therapy with low doses of transdermal estrogen patches and different oral progestogens reduces menopausal symptoms and also safeguards against unwanted pregnancies in the perimenopausal period.

Control of Growth Hormone Secretion during the Postpartum Period

The postpartum period is characterized by high levels of circulating steroids which condition hypothalamo-pituitary activities. In pregnancy growth hormone (GH) levels are greatly increased and lack pulsatility. In order to investigate the behavior of GH during the postpartum period, the GH response to GH-releasing hormone stimulation (50 and 100 micrograms), to amphetamine, a dopamine receptor agonist, and to FK 33-824, an opiate receptor agonist, was investigated in women during the first 5 days after delivery. In all groups GH responses were significantly lower (p less than 0.01) than in normal women studied during the early follicular phase. FK-33-824-induced GH release was similar in postpartum and control women. These results demonstrate reduced pituitary GH response to GH-releasing hormone and to amphetamine in women during the postpartum period, confirming the peculiarity of the hypothalamopituitary component.

Comparison of biochemical markers of bone turnover and bone mineral density in different groups of climacteric women

In the present study we evaluated plasma levels of two markers of bone turnover (osteocalcin (OC) and urinary pyridinium cross-links) in association with bone mineral density (BMI) in different groups of climacteric women. We have investigated 158 women in pre- ,peri- and postmenopause. Blood and urine samples for assay of hormones and markers were collected and bone mineral density (BMD) was measured by DEXA densitometry in the distal tenth of the non-dominant forearm. There was a significant increase in mean absolute levels of both markers in perimenopause and women in natural and surgical menopause, with respect to women in premenopause. There was a significant correlation between OC and deoxypyridoline (DPYR) in peri- and postmenopause groups. In peri- and postmenopause groups ,BMD was correlated with an increase in the biochemical markers of bone remodeling. In the present study ,OC and DPYR were found to have good sensitivity for identifying perimenopausal women with pathological BMD. The present results reveal a positive and significant correlation between DPYR and OC ,inversely proportional to BMD ,during hormone replacement therapy. These markers therefore turn out to be sensitive not only for monitoring severe pathology of bone turnover ,but also for monitoring slight physiological deficits in bone equilibrium beginning in perimenopause.

Thyroid function in early pregnancy I: Thyroid-stimulating hormone response to thyrotropin-releasing hormone

Maternal thyroid function in pregnancy is influenced by many factors. This study was undertaken to clarify the mechanism of thyroid regulation in the first trimester of normal pregnancy. We performed the thyrotropin-releasing hormone (TRH) test in eight women in the first trimester (week 6-9) of pregnancy and ten normal women in early follicular phase. Basal plasma levels of free triiodothyronine and free thyroxine were within the normal range in both groups, whereas thyroid-stimulating hormone (TSH) was at the lower limit of the normal range in pregnant women. TRH stimulation evoked a TSH response with a peak of 14.1 +/- 1.2 mIU/ml at 30 min. In control subjects TSH increased in response to TRH with a peak of 7.4 +/- 1.1 mIU/ml at 30 min. Statistical analysis with Students t test revealed significantly higher TSH levels (p < 0.01) in pregnant women. The most striking finding was the enhanced responsiveness of TSH to TRH stimulation while the thyroid hormones, free triiodothyronine (fT3) and free thyroxine (fT4), remained in the normal range. This response was similar to that observed in central hypothyroidism. These results suggest that the reduction in maternal pituitary TSH levels is due to human chorionic gonadotropin (hCG) inhibition of TRH secretion.