Short‐Term Effects of New Synthetic Conjugated Estrogens on Biochemical Markers of Bone Turnover

Abstract

Fifty early postmenopausal women completed a double-blind, placebo-controlled study evaluating the short-term effect of a new synthetic conjugated estrogens formulation (Cenestin) on bone turnover. Subjects were randomized to either 0.625 mg/day synthetic conjugated estrogens (n = 35) or placebo (n = 15) for 3 months. Biochemical markers were evaluated at baseline (three measurements at Days -2, -1, and 0) and Days 30, 60, and 90. Bone resorption assessed by urinary NTX (-31.4%) and serum CTX (-34.2%) was significantly (p < 0.01) decreased in the estrogen-treated group compared to the placebo group within 1 month of treatment. The mean percent decreases for urinary NTX from baseline during estrogen treatment were -58.0% (p < 0.01 vs. placebo) and -34.1% (ns) after 2 and 3 months, respectively. For serum CTX, the percent changes from baseline were -17.6% (p < 0.01) and -16.9% (p < 0.01) at 2 and 3 months, respectively. As expected, the decrease of both bone formation markers (bone ALP and PINP) was delayed compared to that of bone resorption and significant (p < 0.05-0.01) only after 2 months of treatment in the estrogen-treated group compared to the placebo group. Synthetic conjugated estrogens significantly decreased bone resorption and bone formation comparable to that previously reported for estrogen treatments proven efficacious in preventing postmenopausal bone loss.

The Effects of Synthetic Conjugated Estrogens, A (Cenestin) on Trabecular Bone Structure and Strength in the Ovariectomized Rat Model

“…However, a number of clinical studies of phytoestrogens showed that they were not able to prevent estrogen deficiency bone loss [37][38][39]. When Cenestin was evaluated in a clinical study of estrogen-deficient women, it significantly reduced biochemical markers of bone turnover [6]. A randomized controlled trial of Cenestin is now required to evaluate whether the reduction in bone turnover in postmenopausal, estrogen-deficient women would also prevent bone loss and reduce fracture.…”

“…Cenestin (Duramed Pharmaceuticals, Cincinnati, OH) is a new synthetic conjugated estrogen product for oral administration. The constituents of Cenestin are similar to the nine most common estrogens found in conjugated equine estrogen preparations, but they are synthesized entirely from plant sources (i.e., basic steroid molecules found in soybeans and yams) [6,7]. The US Food and Drug Administration (FDA) has designated this first modified conjugated estrogens-release product made from synthetic sources as Synthetic Conjugated Estrogens, A (SCE).…”

“…Preclinical studies have not been performed with Cenestin, as the FDA considered it to be equivalent to conjugated equine estrogen products. However, a recent short-term clinical study demonstrated that treatment with Cenestin reduced a marker of bone resorption, urinary N-telopeptide (U-NTX), by 30% after 30 days of treatment and that this loss was maintained through the 90-day treatment period [6].…”

Bone Markers - Their Nature and Clinical Use

“…The field where bone markers really show their potential is monitoring of patients, possibly under therapy (10-13), (14)(15)(16). Already 1-2 months after a change in therapy the bone markers clearly indicate whether a patient responds or not.…”