Oral, water-soluble combined estrogen/calcium preparation for postmenopausal therapy

Estrogen is often prescribed for symptoms and sequelae of ovarian estrogen loss after menopause.

To assess efficacy and acceptability of a new, highly soluble estrogen-calcium preparation, we formulated a water-soluble powdered combination of estrogen (0.625 mg estrone piperazine sulfate) and calcium (1 g, ions) as the highly soluble glycerophosphate salt (Estrosol). Effects of once-daily administration on bone mineral turnover of Estrosol dissolved in water (n = 11) was compared with 0.625 mg conjugated estrogens (Premarin) + 1 g calcium (Tums 500 Calcium Supplement) (n = 8). All women had had a previous hysterectomy, were between the ages 40 and 75, within 25% of ideal body weight, and had not taken hormonal preparations for at least 3 months. Assessment of bone mineral turnover was by monitoring N-telopeptides and bone specific alkaline phosphatase (BSAP) on 5 occasions: pretreatment and once during each of the 4 months of treatment.

Mean N-telopeptide values decreased (p = .005) in both groups: Estrosol, 29.2% (40 --> 29 mmol bone collagen equivalents (BCE)/mmol creatinine), and Premarin(R) + calcium, 44.8% (33 --> 18 mmol). Mean BSAP values also decreased (p = 0.007) in both groups: Estrosol, 12.6% (12.06 --> 10.54 mg/l), Premarin(R) + calcium, 19.1% (11.57 --> 9.36 mg/l). The difference between groups for both N-telopeptides and BSAP was not significant, although sample size was small. Symptoms (hot flashes, vaginal dryness) improved similarly in both groups. Symptoms during treatment (breast or nipple tenderness, bloating) also were similar in both groups. Both preparations were well-tolerated. There were no changes in CBC, liver function tests, electrolytes or urinalyses in either group .

This pilot study indicates that the combined, highly water-soluble preparation of estrogen and calcium is effective in reducing bone mineral turnover, acceptable and well-tolerated. Use of this single aqueous preparation may lead to better compliance than using two separate pills.