Clinical applications contraception

The major oestrogen preparations used medically are outlined in Table 1.12, and their chemical structure is illustrated in Figure 1.3. The widest clinical application of oestrogens relate to their use as oral contraceptives. Most such contraceptive pills contain an oestrogen in combination with a progestin (discussed later). 

Progesterone receptor antagonists and their potential clinical applications (e.g. in uterine myoma, endometriosis, breast, ovarian or uterine cancer, or as potential contraceptives) are discussed by Irving M. Spitz. 

Before discussing the clinical application of these steroidal agents it is well to keep in mind the extraordinary efficacy of this mode of contraception. In Table I we present the data assembled by Venning (31) on the relative efficacy of various contraceptive methods. All of those studied in various experimental trials effectively reduced fertility, but the oral contraceptive most extensively studied (the norethynodrel-estrogen combination) is much the most effective. Indeed, the pregnancy rate listed appears to be attributable to failure to use the method properly rather than to a rare physiological exception to the action of the drug. 

The application of the Birch reduction to ethers of estradiol by A. J. Birch opened up the area of 19-norsteroids to intensive research. The major Birch reduction product is an enol ether which affords either a 3-keto-A -or a 3-keto-A -19-norsteroid depending upon the hydrolysis conditions. Various 19-norsteroids have been found to have useful clinical activity compounds (30), (31), and (32) are oral contraceptive agents and compound (33) has been used as an oral anabolic agent. Several of these compounds were prepared on an industrial scale for a number of years by the Birch reduction of estradiol derivatives. 

The first documented use of sUicone as biomaterial was silicone mbber tubing as shunts for treatment of hydrocephalus in about 1955. From 1960 to 1990, the biomedical application of sUicone mbber was steadUy grown. One of the most well-known silicone product is the Norplant contraceptive implant. The first clinical experiment with this device was reported in 1966. FDA approved its use in 1990. 

Between the time of their filing the patent application and its issue, the company was planning several clinical studies when it came to their attention that another issued U.S. patent existed, which was filed before their chemist synthesized the compound of formula I. The patent of concern was directed to steroidal compounds, although it did not disclose their particular compound of formula I, nor did it indicate any specific utility in combination with a progestin for contraception. The patent specification (the entirety of the document) disclosed a number of Markush structures of varying scope as well as a description of the compounds as having utility for the treatment of prostate cancer. Claim 13 from the issued patent is illustrated in Figure 1.5 and it particularly concerned them. 

Brache, V., Cohen, J. A., Cochon, L., and Alvarez, F. (2006), Evaluating the clinical safety of three vaginal applicators A pilot study conducted in the Dominican Republic, Contraception, 73,72-77. 

Prostaglandins have, potentially, very important applications in a wide range of clinical conditions, e.g. in the treatment of hypertension and thrombosis, as well as for contraception, the induction of abortions and the relief of asthma and peptic ulcers. However, much more work needs to be done before they can be put to routine use. 

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