medrogestone and Osteoporosis--Postmenopausal

INDIRECT MECHANISM OF ACTION: Tibolone (OD 14) is the precursor of its active principles that are its metabolites: 3 alpha and 3 beta hydroxylated derivatives. In vivo, the latter behave like estrogens. Certain tissues (liver, endometrium) may metabolize the 3 beta ol derivative into the delta 4 isomer with progestagenic and androgenic activity. The metabolism of the product in other tissues such as the breast and brain is unknown.. At the dose of 2.5 mg/day, the product expresses an estrogen activity equivalent to that observed with classical doses of estrogens in the brain, genito-urinary tract, vascular endothelium and bone. In the brain and muscle, it also has a slightly androgenic effect and in the breast an antiestrogenic effect. ON METABOLIC LEVEL: The product acts like a minor androgen (lowering triglycerides and HDL cholesterol without interfering in the cholesterol cell flow) and it stimulates fibrinolysis. ON CLINICAL LEVEL: Tibolone treats the symptoms of estrogen privation and protects against bone loss, without inducing bleeding or mastodynia. There is a lack of large epidemiological studies on prevention of fracture risks, cardiovascular effects and breast. Tolerance in the population studied was excellent (healthy population). However, tolerance remains to be assessed in particular sub-groups (populations at risk of certains pathologies).

Topics: Adult; Aged; Animals; Blood Coagulation; Breast; Cardiovascular Diseases; Controlled Clinical Trials as Topic; Double-Blind Method; Endometrium; Estradiol; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Humans; Hysterectomy; Lipid Metabolism; Lipids; Medrogestone; Menopause; Middle Aged; Norethindrone; Norethindrone Acetate; Norpregnenes; Osteoporosis, Postmenopausal; Ovariectomy; Placebos; Postmenopause; Progesterone Congeners; Prospective Studies; Rabbits; Rats; Risk Factors; Surveys and Questionnaires; Time Factors

Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women.. Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1 years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiselius's index (AP(CaOx)) and calcium/citrate ratio.. After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2 +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/- 3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively.. Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Topics: Aged; Calcium Carbonate; Calcium Oxalate; Dietary Supplements; Estrogens, Conjugated (USP); Female; Hormone Replacement Therapy; Humans; Kidney Calculi; Medrogestone; Middle Aged; Osteoporosis, Postmenopausal; Risk Assessment

Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss. Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear. In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais.. The subjects consisted of 146 Thai women no more than 6 years postmenopausal. The subjects were randomly allocated to receive 750 mg supplemental calcium alone, calcium and conjugated equine estrogen (CEE) at 0.3 or 0.625 mg, calcium and calcitriol at 0.25 or 0.5 microg daily. Those receiving CEE also took 5 mg medrogestone for 12 days each month. BMD at L2-4 and femoral neck were measured at baseline 1 year and 2 years after treatments. Data were expressed as mean +/- S.E.. Subjects on supplemental calcium alone had approximately 2.5% decreases in L2-4 (P < 0.05) and femoral BMD (P < 0.01) at 2 years. CEE (0.3 mg) resulted in 3.20 +/- 1.2% increase in vertebral BMD (P < 0.05) while no significant change in BMD was demonstrated at the femoral neck. Likewise, 0.625 mg of CEE induced 5.4 +/- 1.4% increase in vertebral BMD at 2 years (P < 0.001) without change in the femoral BMD. In regard to calcitriol, no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol.. We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais. It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement.

Topics: Absorptiometry, Photon; Bone Density; Calcitriol; Calcium; Calcium Channel Agonists; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Femur Neck; Follow-Up Studies; Humans; Lumbar Vertebrae; Medrogestone; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Progesterone Congeners; Thailand

To evaluate the effectiveness of transdermal oestrogen replacement therapy plus medrogestone (HRT) in postmenopausal bone loss prevention by means of US.. We enrolled 112 healthy postmenopausal women in an open, prospective study. These women, after a gynaecological evaluation and an US assessment of the skeletal status, were advised to take cyclic sequential oestrogen/progestagen therapy: 50 microg/day of transdermal 17beta-oestradiol (Rotta Research Laboratorium) plus 5 mg/day of medrogestone, for 12 days per cycle (Wyeth-Ayerst). After 1 year we recalled these women: only 32 of them were taking HRT, while 49 had declined HRT without taking alternative therapies. The remaining women were excluded from the study as they were either unavailable for the check-up or they were taking prohibited therapies. We used DBM Sonic 1200 (Igea, Italy) to assess US parameter changes at phalanxes at enrollment and after 1 year. This device enabled us to evaluate US transmission velocity (AD-SoS) and US attenuation pattern (UBPS). In a previous study we had evaluated the intra- and inter-observer reproducibility of AD-SoS measurements (0.4 and 1.0% respectively). Using the same data we evaluated the intra- and inter-observer precision of UBPS.. The UBPS intra-operator reproducibilities were 5.3% and 6.1% (for the 1st and the 2nd operator, respectively), while inter-observer precision was 8.8%. Both AD-SoS and UBPS significantly decreased in the non-user group(-0.7%, P < 0.001 and -14.3%, P < 0.001 respectively). In the user group AD-SoS showed a significant increase (+0.7%, P < 0.01), while a slight but significant decrease was observed for UBPS (-2.8%, P < 0.05).. Our findings show that the effectiveness of transdermal HRT in slowing or even arresting postmenopausal bone loss can be monitored by quantitative US studies. The trend difference observed between AD-SoS and UBPS with and without therapy is at least partially explained by a different response to HRT with regard to bone density as well as structure.

Topics: Administration, Cutaneous; Bone and Bones; Estradiol; Estrogen Replacement Therapy; Female; Humans; Medrogestone; Osteoporosis, Postmenopausal; Progesterone Congeners; Prospective Studies; Ultrasonography

In this study menopausal symptoms, endometrial histology, uterine bleeding pattern, plasma lipid concentrations, bone mineral loss, body weight and blood pressure have been evaluated in postmenopausal women who received continuous conjugated equine estrogens and medrogestone over a 1 year treatment period. By the third month of therapy we detected a significant (p < 0.01) improvement in postmenopausal symptomatology. At the 6th and 12th month, endometrial biopsy specimens revealed atrophic endometrium in all women. Uterine bleeding episodes were observed especially during the first months of treatment. Amenorrhoea was found in all patients only after 8 months of therapy. By the 6th month of therapy, we observed a significant (p < 0.01) decrease of plasma cholesterol and low-density lipoprotein cholesterol levels. Instead, plasma high-density lipoprotein and triglycerides concentrations didn't show significant variation from baseline values. No significant changes in bone mineral density could be detected after 12 months of treatment. Body weight and blood pressure were not significantly altered from baseline. This study suggests that continuous conjugated equine estrogens plus medrogestone treatment appears to be an interesting and safe manner to administer postmenopausal hormone replacement therapy. This regimen could represent a good alternative to sequential estroprogestin therapy in women who do not tolerate withdrawal bleeding.

Topics: Amenorrhea; Atrophy; Biopsy; Dose-Response Relationship, Drug; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Lipoproteins; Medrogestone; Middle Aged; Osteoporosis, Postmenopausal; Triglycerides; Uterine Hemorrhage