A comparison of circulating hormone levels in postmenopausal women receiving hormone replacement therapy Raymond W. Jurgens, Jr., PhD,. Laurence J. Downey, MD,. William D. Abernethy, BS,. Neal R. Cutler, MD: and Julie Conrad, RN b Marietta, Georgia, and Beverly Hills, California Seventeen postmenopausal subjects were randomized into this comparative study of esterified estrogen 0.625 mg (Estratab), esterified estrogen 0.625 mg plus 1.25 mg methyltestosterone (Estratest H.S.), or conjugated estrogen 0.625 mg (Premarin). Sixteen subjects completed the study in which plasma hormone concentrations of estrone and estradiol were assessed at various time points. There were no significant differences among the treatment groups. (AM J OSSTET GYNECOL 1992;167:459-60.)

Key words: Hormone levels, postmenopausal women, hormone replacement therapy

There are many different products available to clinicians for the treatment of postmenopausal symptoms, as well as a number of therapeutic regimens.' Each product has been shown to have particular benefits and allow for individual needs and concerns of patients, as well as their physicians. Management of postmenopausal symptoms usually includes oral estrogen, progestogen, and androgen formulations currently marketed. Whereas a number of estrogen formulations have been prescribed for decades, there is little comparative information available on the differences in potencies and pharmacologic effects. Some laboratories have measured free and total plasma estradiol and estrone levels during a 25-day administration of estrone sulfate and estradiol. Others have correlated estrogenic potency with hepatic protein production after administration of various oral, transdermal, and vaginally delivered estrogen preparations." The purpose of this study was to measure and compare plasma levels of estrone and estradiol in postmenopausal women after the administration of commercially available oral esterified or conjugated estrogen products.

Patients and methods The investigation was approved by the local human investigation committee and informed consent was obtained. Seventeen postmenopausal subjects (14 natural and three surgical) entered the study. The demographic characteristics were similar across the three From the Clinical Research Group, Solvay Pharmaceuticals, Marietta," and California Clinical Trials, Beverly Received for publication December 17, 1991; revised March 30, 1992; accepted April 15, 1992. Reprint requests: Raymond W. Jurgens, Jr., PhD, Director, Clinical Research, Phase IV, Solvay Pharmaceuticals, 901 Sawyer Road, Marietta, GA 30062. 611138776

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Table I. Levels of follicle-stimulating hormone Follicle-stimulating hormone (mIU Iml) Subject identifier

Treatment group

Screening

60178 60180 60183 60188 60190 60193 60177 60182 60184 60187 60189 60179 60181 60185 60191 60192

Estratab Estratab Estratab Estratab Estratab Estratab Premarin Premarin Premarin Premarin Premarin Estratest H.S. Estratest H.S. Estratest H.S. Estratest H.S. Estratest H.S.

99.6 82.3 65.8 64.9 73.2 78.3 60.2 91.6 157.4 109.1 128.6 151.1 89.4 143.3 109.3 141.6

I

Day 29

*

45.3 54.0 59.3 40.3 57.8 22.2 63.1 83.1 66.9 83.9 86.1 73.3 69.1 62.9 87.4

*Data not available. treatment groups. Mean age was 53.95 years with a range of 37.9 to 65.8 years. Two patients presented with menopausal symptoms at screening. At baseline (after washout) six patients were experiencing menopausal symptoms. Seventy-one percent of the subjects were white and 29% were categorized as other (Hispanic, n = 3; black, n = 1). Subject 60186 did not meet inclusion-exclusion criteria and was dropped from the study shortly after treatment was begun. After patient randomization, blood samples were taken from patients at baseline and 8 hours after the first dose of drug. Patients returned to the clinic weekly for 5 weeks while taking medication at the same time daily after their morning meal. Blood samples were drawn 8 ± 2 hours after the dose of study medication at each clinic visit for assay of plasma hormone levels. The plasma follicle-stimulating hormone level was de-

459

460 Jurgens et al.

August 1992 Am J Obstet Gynecol

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Estratab

500

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Premarin _

200

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