Prolonged melatonin administration decreases nocturnal blood pressure in women.

BACKGROUND: The nocturnal decline of blood pressure (BP) is almost coincident with the elevation of melatonin, which may exert vasodilatating and hypotensive effects. In this study we investigated whether prolonged nocturnal administration of melatonin could influence the daily rhythm of BP in women. METHODS: In a randomized double-blind study, 18 women, 47 to 63 years of age and with normal BP (N = 9) or treated essential hypertension (N = 9), received a 3-week course of a slow-release melatonin pill (3 mg) or placebo 1 h before going to bed. They were then crossed over to the other treatment for another 3 weeks. In each woman ambulatory BP was recorded for 41 h at baseline at the end of each treatment period. RESULTS: In comparison with placebo, melatonin administration did not influence diurnal BP but did significantly decrease nocturnal systolic (-3.77 +/- 1.7 mm Hg, P = .0423), diastolic (-3.63 +/- 1.3 mm Hg, P = .0153), and mean (-3.71 +/- 1.3 mm Hg, P = .013) BP without modifying heart rate. The effect was inversely related to the day-night difference in BP. CONCLUSION: These data indicate that prolonged administration of melatonin may improve the day-night rhythm of BP, particularly in women with a blunted nocturnal decline.

A comparison of the central effects of different progestins used in hormone replacement therapy.

OBJECTIVE: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. METHODS: Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50 microg per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n = 20), medroxyprogesterone acetete (MPA; 10 mg per day; n = 20), nomegestrol acetate (NMG; 5 mg per day; n = 20) or norethisterone acetate (NETA; 10 mg per day; n = 20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. RESULTS: All progestins except DYD increased (P < 0.0001) BBT by 0.3-0.5 degrees C. Anxiety was decreased by DYD (- 2.3 + 1.1; P < 0.01) and MPA (- 1.5 + 0.5; P < 0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (- 3.0 + 0.7; P < 0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group (P < 0.05 ). CONCLUSIONS: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy.

Administration of tibolone decreases 24 h heart rate but not blood pressure of post-menopausal women.

OBJECTIVE: Elevation of blood pressure and heart rate increase the risk of cardiovascular disease. Administration of estrogens does not affect heart rate but may decrease 24 h blood pressure. In this study, we tested the effect of the estro-progestogenic compound tibolone. METHODS: Thirty healthy, post-menopausal women were randomized to receive placebo (n = 15) or tibolone, at the commonly prescribed dose of 2.5 mg per day (n = 15). Before and after 6 months of treatment, in each woman blood pressure and heart rate were monitored every 30 min for 41 h by an ambulatory device. Valuable readings were those collected from 8:00 a.m. of the second day to 8:00 a.m. of third day. Analyses were performed of 24 h, day-time (7:00 a.m.-11:00 p.m.) and night-time (11:00 p.m.-7:00 a.m.) values. Day to night difference was also calculated. RESULTS: Placebo did not modify 24h, day-time, and night-time blood pressure or heart rate values. Day-night differences were also not affected by placebo. Similarly to placebo, tibolone administration did not modify any of the blood pressure parameters taken into consideration. By contrast, a significant decline of 24 h heart rate (73.2 +/- 2.3 beats/min versus 69.3 +/- 1.7 beats/min; P < 0.0008) was observed. The effect was significant both at day (76.6 +/- 2.4 beats/min versus 72.1 +/- 1.9 beats/min; P < 0.0001) and night (65.8 +/ 2.6 beats/min versus 62.4 +/- 1.9 beats/min; P < 0.05). Day-night blood pressure and heart rate differences were not affected by tibolone. CONCLUSIONS: In post-menopausal women, administration of tibolone does not influence 24 h blood pressure but reduces heart rate.

Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women.

Genetic hyperhomocysteinemia is associated with skeletal abnormalities and osteoporosis. We tested whether levels of homocysteine and critical co-enzymes of homocysteine metabolism, such as vitamin B12 and folate, are related to lumbar spine bone mineral density (BMD) measured by DEXA in 161 postmenopausal women. Folate but not homocysteine or vitamin B12, was lower in osteoporotic than normal women (7.2 +/- 0.9 ng/L vs 11.4 +/- 0.7 ng/L, P < 0.003). Folate, but not homocysteine or vitamin B12, was independently related to BMD (r = 0.254, P < 0.011). BMD progressively increased from the lowest to the highest folate quartile (1.025 +/- 0.03 g/cm2 vs 1.15 +/- 0.03 g/cm2, P < 0.01) even when covaried for weight, which was the only other variable related to BMD. The present data suggest a major association between folate and bone mineralization.