Estrogen preparations available

Many systemically administered estrogen products are available in the United States, but conjugated equine estrogens (CEEs), prepared from the urine of pregnant mares, is the most widely prescribed. Transdermal estrogen preparations are also available and usually are prescribed for patients who experience adverse effects, elevated triglycerides, or liver function abnormalities while taking an oral product. Transdermal preparations also have a lower incidence of venous thromboembolism than oral preparations.9... 

Using a preemptive approach, Lebo et al. (2004) have shown that oleic acid and methyl oleate can be removed from triolein prior to use of the triolein in SPMDs (see Chapters 4 and 5). Dialysates from SPMDs prepared using triolein purified by the Lebo et al. (2004) method exhibited lower acute toxicity (Microtox assay) than SPMDs prepared with unpurified triolein. Also, the YES assay demonstrated that the purification method had removed all background estrogenic activity from SPMD extracts. Eor these reasons, the use of triolein purified by the method of Lebo et al. (2004) is standard for all SPMD studies conducted at CERC, USGS. Also, SPMDs with triolein purified by the Lebo et al. (2004) method are available from the commercial vendor upon request. 

Three forms of purified FSH are available. Urofollitropin, also known as uFSH, is a purified preparation of human FSH that is extracted from the urine of postmenopausal women. Virtually all the LH activity has been removed through a form of immunoaffinity chromatography that uses anti-hCG antibodies. Two recombinant forms of FSH (rFSH) are also available follitropin alfa and follitropin beta. The amino acid sequences of these two products are identical to that of human FSH. They differ from each other and urofollitropin in the composition of the carbohydrate side chains. The rFSH preparations have a shorter half-life than preparations derived from human urine but stimulate estrogen secretion at least as efficiently and, in some studies, more efficiently. The rFSH preparations are considerably more expensive. 

The estrogen-containing compounds are arranged in order of increasing content of estrogen. Other preparations are available. (Ethinyl estradiol and mestranol have similar potencies.)... 

A large number of oral contraceptives containing estrogens or progestins (or both) are now available for clinical use (Table 40-3). These preparations vary chemically and pharmacologically and have many properties in common as well as definite differences important for the correct selection of the optimum agent. 

A number of other, more specialized systems are available to the reproductive toxicologist to answer specific mechanistic questions. In particular, the hormonal control of reproductive function and its perturbation by toxicants have received much attention. Such investigations can use intact cells to investigate the downstream consequences of toxicants on hormone-receptor interactions or use cells that respond to specific hormones (e.g., the MCF-7 breast cancer cell line and estrogen Soto et al., 1995). Receptor biology/ligand binding can be examined in membrane preparations of specific cell types or in recombinant cell systems (e.g., human and yeast cells Klein et al.,... 

In the nonpregnant, postpubescent female, production of estrogen and progesterone is not tonic in nature but follows a pattern or cycle of events commonly referred to as the menstrual cycle. The menstrual cycle usually occurs over a 28-day period. The primary function of this cycle is to stimulate the ovaries to produce an ovum that is available for fertilization, while simultaneously preparing the endometrium of the uterus for implantation of the ovum, should fertilization occur. These events are illustrated in Figure 30-2. The cycle is characterized by several specific phases and events that are briefly outlined below. A more detailed description of the regulation of female reproduction can be found in several sources listed at the end of this chapter.33,88 94 113... 

Therapeutically used types of estrogens and prog-estins are listed in Tables 30-4 and 30-5. Both types of hormones can be administered in their natural form (estradiol and progesterone), and several synthetic derivatives of each type are also available. Most of the drugs listed in Tables 30-4 and 30-5 are available as oral preparations, and many conditions can be conveniently treated by oral administration. These hormones may also be administered transdermally via patches, creams, or gels the transdermal route may offer certain advantages, such as decreased side effects and liver problems.86,130 Certain preparations can be... 

Because of the beneficial effects of the vaginal delivery of estrogens and progesterone in comparison to their oral delivery, various vaginal preparations (tablets, suppositories, gels, rings) of these agents are now available, for use ... 

Estrogens arc commercially available in a wide variety of dosage fonns oral tablets, vaginal creanrs and foams, irans-demial patches, and iniromascular dosage preparations. 

I Oral Estrogen. Oral CEE has been available for more than 50 years. CEE is prepared from the urine of pregnant mares and is composed of estrone sulfate (50% to 60%) and multiple other equine estrogens such as equilin and 17a-dihydroequilin. ... 

Testosterone is available as oralmethyltestosterone in the United States and as testosterone implants in the United Kingdom. Of the available oral preparations, methyltestosterone in combination with esterifled estrogen (either 0.625 mg esterifled estrogen plus 1.25 mg methyltestosterone or 1.25 mg esterifled estrogen plus 2.5 mg methyl-testosterone) is the most widely studied. 

One can reasonably hope that rapid ultrasensitive methods based on the isotope-displacement method will soon be available for the principal estrogens. A promising method has been published by Korenman (Kll). The reliability of this assay and the ease of preparation of the uterine macromolecule used in this assay remain to be established. 

A number of foodstuffs and plant-derived products, largely from soy, are available as nonprescription items and often are touted as providing benefits similar to those from compounds with established estrogenic activity. These products may contain flavonoids such as genistein, which display estrogenic activity in laboratory tests, albeit generally much less than that of estradiol. In theory, these preparations could produce appreciable estrogenic effects, but their efficacy at relevant doses has not been established in human trials. 

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