Preparations for postmenopausal hormone therapy

INTRODUCTION

Estrogen therapy in postmenopausal women relieves menopausal symptoms, but has risks for some women, including breast cancer, coronary heart disease, stroke, and venous thromboembolism (see "Postmenopausal hormone therapy: Benefits and risks". For most peri- and postmenopausal women, postmenopausal hormone therapy (HT) is still a good option for management of menopausal symptoms. This topic will review the available estrogen and progestin preparations, as well as some alternatives to these hormones. Recommendations for the use of estrogen therapy are discussed separately. (See "Treatment of menopausal symptoms with hormone therapy".)

ESTROGEN PREPARATIONS

Once a decision has been made to treat a postmenopausal woman with estrogen, consideration should be given to the type of estrogen and the route by which it is to be given, as well as the need for progestin and the most appropriate progestin regimen. Estrogen is available in many forms: oral, transdermal, topical gels and lotions, intravaginal creams and tablets, and vaginal rings. In some countries estrogen can also be given as a subcutaneous implant [1].

Systemic estrogen — Systemic estrogen is most often administered orally or transdermally (table 1). There are several important differences in the effects of these preparations.

• Estrogen administered orally has a greater effect on the liver due to the first-pass effect, because intestinal absorption leads to portal vein concentrations that are initially substantially higher than those after transdermal administration. Thus, oral estrogen administration increases hepatic production of thyroxine-binding globulin, corticosteroid-binding globulin, sex hormone-binding globulin, triglycerides, high-density lipoprotein (HDL) cholesterol, and clotting factors, whereas their production is only minimally increased by transdermal estrogen administration [2,3]. Furthermore, the saturation of bile with cholesterol is adversely affected by oral, but not transdermal, estrogen [4]. Thus, transdermal estrogen is preferred in those women in whom it is important to minimize these effects. All of the progestin regimens described below are effective for the prevention of endometrial cancer, whether oral or transdermal estrogen is used [5].
• Transdermal estrogen is as effective as oral estrogen in preserving bone density (graph 1) [6] and in treating menopausal symptoms [7]. In addition, when compared to oral estrogen, transdermal estrogen may decrease fat mass and increases lean body mass [8]. Transdermal estrogen administration has less of an effect on serum lipid concentrations when compared to a comparable dose of oral estrogen [2,3,9]. (See "Postmenopausal hormone therapy and cardiovascular risk", section on 'Lipids'.)

The different oral estrogens have similar efficacy. Conjugated equine estrogen and estrone sulfate are absorbed from the gastrointestinal tract primarily as estrone sulfate, which is biologically inactive. Oral estradiol is converted to estrone and then estrone sulfate in liver and other tissues.The estrone sulfate is then continuously desulfated and converted to estradiol. Therefore, even though oral estrogen is administered in a single daily dose, the resulting serum estradiol concentrations vary little between doses.