Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimenopausal women.

OBJECTIVE: The menopause transition is characterized by luteal phase defect anovulatory cycles, and changes in body weight and body composition. Resting metabolic rate (RMR) is increased in the luteal phase of the menstrual cycle. We evaluated whether progestin administration increases RMR and influences body composition of perimenopausal women. DESIGN: Thirty-six perimenopausal women were randomly allocated to receive either calcium (1 g/day) continuously plus the progestin nomegestrol acetate (NOMAc; 5 mg/day for 10 days x month for 12 months) or calcium alone. Body composition, RMR, energy intake, and climacteric and psychological symptoms were evaluated at baseline and after 12 months. In the NOMAc group, body composition and RMR analyses were performed twice during the first month of treatment. One evaluation was performed after almost 8 days of NOMAc adjunct, and an another before or almost 15 days after NOMAc administration. RESULTS: Resting metabolic rate was increased by NOMAc administration of 54.5 +/- 73.8 kcal/24 h (P < 0.01). In women treated with NOMAc, fat mass decreased by 1.2 +/- 0.6 kg (P < 0.001). In comparison with controls, body weight (P < 0.05) and body mass index (P < 0.05) were also reduced after 12 months of therapy with NOMAc. CONCLUSIONS: In perimenopausal women the use of NOMAc increases RMR. During the menopause transition, cyclic NOMAc administration may contribute to reduce negative modification of body composition.

Interplay between maternal weight and seasons in determining the secondary sex ratio of human offspring.

When gender of 9,284 single fetuses, which were delivered at term in the Policlinic of Modena between 1997-2001, was stratified for month of conception and for quartiles of pregravid maternal weight, it showed that the ratio of male to female fetuses (secondary sex ratio) was characterized by a clear seasonal variation that was modulated by pregravid maternal weight. Two seasonal peaks of sex ratio (March and October +/- 31 days) were observed in mothers in the lowest two quartiles of prepregnancy body weight (< or =62 kg), and one single peak (October +/-36 days) was observed in mothers with preconception weight in the upper two quartiles.

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.

Comparison of the effect of oral and transdermal hormone therapy on fasting and postmethionine homocysteine levels.

OBJECTIVE: To compare the modifications on basal and post-methionine homocysteine (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy (HT). DESIGN: Prospective randomized study. SETTING: Outpatient service at university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and 140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2) and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations. RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2] micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032; 0.093] micromol/L) was observed. Modifications were similar in the transdermal and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5; 75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8] micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post-methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces post-methionine Hcy and fasting Hcy when it is elevated.

Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells.

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy. However, unacceptable cytotoxicity and genotoxicity on normal cells often impairs the proper management of patients. Phosphoaminothiol WR-1065, the active metabolite of amifostine, appears to protect normal cells and tissues against cytotoxic exposure to radiation or chemotherapeutic agents. Nevertheless, there is disagreement in findings on amifostine protection against bleomycin-induced severe side effects which have suggested that amifostine effectiveness against bleomycin-induced genotoxicity in normal leukocytes and tumour line cells K562 be studied. DNA damage was detected by single cell gel electrophoresis (or Comet) assay, a technique able to detect DNA strand breaks, alkali-labile sites and incomplete excision repair events in individual cells and which appears to be an ideal tool for assessing variability in response of different cell types in vitro. WR-2721 appears to selectively protect healthy leukocytes but not K562 tumoral cells. On the other hand, data on the inter- and intra-individual sensitivity to bleomycin and amifostine suggest that individual metabolic/genetic differences and other factors relating to lifestyle may be responsible for response variability. Application of the Comet assay in appropriate clinical settings to test the sensitivity of patients when undergoing chemotherapy appears possible.