Search

Sex steroids play an important role in the maintenance of bone density in men and women, but the circulating, biologically active unbound fraction is influenced by the concentration of sex hormone binding globulin (SHBG). SHBG increases with advancing age in men and leads to a reduction in serum free testosterone and oestradiol, which may then affect bone turnover, bone mineral density (BMD) and the risk of fractures. We have therefore measured total and unbound sex steroids, SHBG, bone turnover markers and BMD in 57 men with symptomatic low trauma vertebral fractures and 57 age-matched male control subjects. Fasting blood and urine samples were collected from all subjects, who also underwent BMD measurement of the lumbar spine and hip. Serum testosterone, oestradiol, SHBG, bone specific alkaline phosphatase (bone ALP) and urine free deoxypyridinoline/creatinine ratio (fDPD/Cr) were measured. Free sex steroid concentrations were calculated using their ratio with SHBG and albumin and bioavailable testosterone was measured using radioimmunoassay. The two groups were then compared and regression models developed to determine the best predictors of BMD and fracture. Men with vertebral fractures had significantly lower weight and BMD at all sites than control subjects (p<0.0001). Serum total testosterone and oestradiol did not differ between the two groups, but calculated free androgen and free oestradiol indices were lower in the fracture group than the control subjects (p=0.04), due to higher SHBG (46.6 versus 36.1 nmol/L: p=0.005). The men with vertebral fractures had significantly higher mean bone ALP (15.8 versus 11.8 microg/L: p=0.002) and fDPD/Cr (5.5 versus 4.0 nmol/mmol: p=0.03). Stepwise multiple regression analysis in both fracture and control groups found body weight to be the best predictor of BMD. In the fracture group weight predicted between 19.7 and 30.7% of the variance in BMD and in control subjects this was between 12.3 and 13.2%. SHBG contributed to the model for hip BMD in the fracture group alone, so that weight and SHBG together accounted for 32 to 42.9% of the variance. A model combining BMD at the spine, total femur and femoral neck with height loss best predicted fracture. In conclusion, men with symptomatic vertebral fractures have higher SHBG and lower calculated free sex steroid indices, increased bone turnover and lower BMD. Whilst body weight was the best predictor of BMD, symptomatic vertebral fracture was best predicted by BMD and height loss.

Background and Purpose: Female sex hormones may protect pre-menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17beta-estradiol, on ischaemia-induced cardiac arrhythmias and on the L-type Ca2+ current (ICaL)., Experimental Approach: In vivo experiments were performed in pentobarbital-anaesthetized rats subjected to acute coronary artery occlusion. ICaL was measured by the whole-cell patch-clamp technique, in rat isolated ventricular myocytes., Key Results: Acute intravenous administration of 17beta-estradiol as a bolus dose followed by a continuous infusion, commencing 10 min before coronary artery occlusion, had dose-dependent antiarrhythmic activity. In female rats 300 ng kg(-1) + 30 ng kg(-1) min(-1) 17beta-estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17beta-estradiol was required to cause similar effects in male rats. In vitro 17beta-estradiol reduced peak ICaL in a concentration-dependent manner. The EC50 was ten-fold higher in male myocytes (0.66 microM) than in females (0.06 microM)., Conclusions and Implications: These results indicate that 17beta-estradiol has marked dose-dependent antiarrhythmic activity that is greater in female rats than in males. A similar differential potency in blocking ICaL in myocytes from female and male rats can account for this effect. This provides an explanation for the antiarrhythmic activity of 17beta-estradiol and gender-selective protection against sudden cardiac death.

To investigate the effect of changes in sex hormone concentration on muscle strength and the bioavailability of 17-beta oestradiol (oestradiol) and testosterone, seven eumenorrheic females were tested during two phases of the menstrual cycle. Maximum voluntary isometric strength of the first dorsal interosseus muscle was measured during the early follicular and mid-luteal phases of the menstrual cycle. These phases were chosen for testing as the concentration of total oestradiol is significantly different in these two phases. Total oestradiol has been repeatedly associated with changes in muscle strength in females, whereas the effects of bioavailable oestradiol are unknown. The concentrations of total and bioavailable oestradiol and testosterone were measured in addition to the concentration of total progesterone. Concentrations of total progesterone and oestradiol were significantly different between the early follicular and mid-luteal phases of the menstrual cycle (P <0.05 and P <0.001 respectively). The concentration of total testosterone (0.7+/-0.2 and 0.8+/-0.1 nmol.l(-1) respectively) and the ratio of total oestradiol to progesterone (153.0+/-251.2 and 108.5+/-27.8 respectively) did not change significantly between the early follicular and mid-luteal phases. Bioavailable testosterone (102.2+/-66.3 and 105.0+/-90.2 pmol.l(-1) respectively) and bioavailable oestradiol (90.5+/-35.5 and 120.0+/-60.6 pmol.l(-1) respectively) did not differ significantly between phases. There were no significant differences in muscle strength during the menstrual cycle (P =0.1). Mean maximum voluntary isometric force of the first dorsal interosseus muscle did not correlate significantly with the mean concentration of any reproductive hormone measured. These results indicate that cyclical variation in endogenous reproductive hormones does not affect muscle strength.

Objective: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients., Design: Prospective clinical study., Setting: A tertiary infertility clinic., Patients: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure., Interventions: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle., Main Outcome Measure: Pulsatility index of the uterine arteries., Results: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42)., Conclusion: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Objectives: To study the relationship between cervical mucus (CM) quality, postcoital test (PCT) results and plasma estradiol (E2) in clomiphene citrate (CC)-treated women. A subsidiary aim was to study the relationship between CM quality and plasma progesterone (P)., Design: Untreated women were compared with oligo-ovulatory patients given CC., Setting: Infertility Clinic, Fazakerley Hospital, United Kingdom., Patients, Participants: Fifty-one untreated patients and 31 women given CC., Interventions: The treated women were given 50 mg/d CC from days 2 to 6 of their cycle., Main Outcome Measures: A CM assessment, a PCT, plasma E2, and P were performed at the anticipated time of ovulation based on at least two previous basal body temperature charts and menstrual patterns., Results: In untreated women there was a very strong tendency for CM quality to improve with rising plasma E2 levels and to worsen with rising plasma P levels. There was a significant association between CM quality and PCT results. Similar results were found in CC-treated women, except that plasma E2 was very significantly higher and there was a significant inverse relationship between plasma E2 and CM quality., Conclusion: High plasma E2 in the periovulatory phase in CC-treated women is a marker for increased sensitivity to and continuing action of the antiestrogen. This impairs the quality of the CM.

Background and purpose: Female sex hormones may protect pre-menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17β-estradiol, on ischaemia-induced cardiac arrhythmias and on the L-type Ca2+ current (ICaL). Experimental approach: In vivo experiments were performed in pentobarbital-anaesthetized rats subjected to acute coronary artery occlusion. ICaL was measured by the whole-cell patch-clamp technique, in rat isolated ventricular myocytes. Key results: Acute intravenous administration of 17β-estradiol as a bolus dose followed by a continuous infusion, commencing 10 min before coronary artery occlusion, had dose-dependent antiarrhythmic activity. In female rats 300 ng kg-1 + 30 ng kg-1 min-1 17β-estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17β-estradiol was required to cause similar effects in male rats. In vitro 17β-estradiol reduced peak ICaL in a concentration-dependent manner. The EC50 was ten-fold higher in male myocytes (0.66 μM) than in females (0.06 μM). Conclusions and implications: These results indicate that 17β-estradiol has marked dose-dependent antiarrhythmic activity that is greater in female rats than in males. A similar differential potency in blocking ICaL in myocytes from female and male rats can account for this effect. This provides an explanation for the antiarrhythmic activity of 17β-estradiol and gender-selective protection against sudden cardiac death. [ABSTRACT FROM AUTHOR]