Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level.

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women.

Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue.

Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones in postmenopausal women.

A. Absorption

Synthetic conjugated estrogens, B are soluble in water and are well absorbed from the gastrointestinal tract after release from the drug formulation. ENJUVIA tablets release synthetic conjugated estrogens, B slowly over a period of several hours. Table 1 and Table 2 summarize the mean pharmacokinetic parameters for unconjugated (free) and conjugated (total) estrogens following single administration of two 0.625 mg tablets to 21 healthy postmenopausal women under fasting conditions. The effect of food on the bioavailability of synthetic conjugated estrogens, B following administration of ENJUVIA tablets has not been studied. However, the presence of food did not significantly affect the pharmacokinetics of a similar formulation of synthetic conjugated estrogens, B.

Table 1. Mean Pharmacokinetic Parameters of Unconjugated (Free) Estrogens Following a Single Dose of 2 x 0.625 mg ENJUVIA Tablets Under Fasting Conditions*

Table 2. Mean Pharmacokinetic Parameters of Conjugated (Total) Estrogens Following a Single Dose of 2 x 0.625 mg ENJUVIA Tablets Under Fasting Conditions

B. Distribution

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