Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients.

Forty-five subjects (41 women and 4 men) in long-stay and medium-stay facilities, aged 74 to 95 years (mean 86.4 years), with 25-hydroxy-vitamin D levels less than 12 ng/ml, were treated for six consecutive months with two tablets per day of a preparation containing vitamin D3 (800 IU/day) and calcium carbonate (1 g elemental calcium/day). Serum levels of 25-hydroxy-vitamin D were very low at baseline (5.6 +/- 0.4 ng/ml) and rose significantly under treatment, to normal values, 33.2 +/- 1.2 and 40.9 +/- 2.1 ng/ml after three and six months, respectively (p < 0.001 for both comparisons). Serum calcium increased significantly, by 4.5% (p < 0.001) during the first three months, and remained at a plateau thereafter. Corrected serum calcium rose by 8.9% (p < 0.001) during the trial. No patient developed hypercalcemia. Serum parathyroid hormone levels, which were elevated at baseline (71.6 +/- 5.8 pg/ml; normal, 12 to 54 pg/ml), decreased gradually and significantly throughout the treatment period, by 43.0% and 67.1% after three and six months, respectively (p < 0.001 for both comparisons). Serum alkaline phosphatase activity fell concomitantly, by 9.9% after three months (p < 0.01) and 36.5% after six months (p < 0.001). In conclusion, the preparation used in our study is effective in correcting both the vitamin D deficiency that is prevalent in elderly institutionalized patients and the resultant increase in bone turnover.

Effects of nomegestrol acetate on carbohydrate metabolism.

The effects of nomegestrol acetate on carbohydrate metabolism were investigated in 20 premenopausal women presenting with menstrual disturbances. The progestogen was administered from day 5 to day 24 of the cycle, over six consecutive cycles, at a dosage (5 mg/d) known to inhibit ovulation. A 3 hour oral glucose tolerance test (OGTT) was performed prior to the hormonal intake and at 3 months and 6 months of therapy. Blood glucose and insulin were measured before and for 3 hours after a 75 g glucose load, and the glucose and insulin areas under the curves (AUC) were calculated. The fasting glycosylated hemoglobin and fructosamine were also determined. Treatment did not induce any significant changes in plasma glucose or insulin glucose values during the oral glucose tolerance test, in glucose and insulin areas under the curves or in glycosylated protein levels. Two women with impaired glucose tolerance were not worsened during therapy. These data suggest that nomegestrol acetate is free from adverse effects on glucose tolerance after 6 months treatment.

Lipolytic activity of progesterone and synthetic progestins on rat parametrial adipocytes in vitro.

Despite the known lipogenic properties of progesterone (P) in vivo, one study had previously reported a direct in vitro lipolytic activity of P on isolated adipocytes from rat parametrial adipose tissue (Sutter-Dub et al., 1981). The aim of the present study was to further investigate this finding. Parametrial, but not retroperitoneal adipocytes, isolated from 6-week-old female rats, showed an increase in glycerol release under P stimulation. Estrone, estradiol, estriol and testosterone were inactive. At 12 weeks of age, parametrial adipocytes were bigger and failed to respond to P. P-stimulated glycerol release was concentration-related between 10(-7) M and 10(-5) M. Compared to norepinephrine, P activity displayed less potency (EC50 around 5 X 10(-7) M vs. 10(-6) M, and 4-fold vs. 2-fold maximal stimulation, respectively). Compared to P, synthetic progestins used in therapeutics (medroxyprogesterone acetate, norethindrone acetate, megestrol acetate and nomegestrol acetate) were more active at 10(-7) M but did not induce a greater response at 10(-5) M. Some 17 alpha-hydroxy and 17 alpha-acetoxy derivatives of P or 19-norprogesterone were also tested at 10(-5) M. General agreement was found between experimental lipolytic activities and known progestative agonist properties, with the exception of 19-norprogesterone, which showed a reduced lipolytic activity compared to P, in contrast with its usually higher progestative potency. The direct in vitro lipolytic activity of P was characterized as specific of age and of the parametrial adipose tissue, concentration-related, and common to synthetic progestins.

Effects of progestogens on lipemia and lipolysis in rat: effects of progesterone, megestrol acetate, norethindrone acetate, and nomegestrol acetate.

Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO. MEG, a 17 alpha-hydroxyprogesterone derivative, induced significant increases in glucose, total and high-density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19-nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19-norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged. The results of this study confirm interest in the therapeutic class of 19-norprogesterone-derived progestogens, exemplified by NOM, with respect to their lack of metabolic side effects.