Oral contraceptive production

Prominent among toxicants that adversely affect both male and female reproductive systems are endocrine disruptors (see Section 9.7). Toxicants that mimic the actions of sex hormones are agonists, and those that prevent hormonal action or bind competitively to hormone receptor sites are antagonists,12 Male patients treated with cimetidine for peptic ulcers have exhibited low sperm counts and abnormal breast enlargement, a condition called gynecomastia. Gynecomastia has also been caused in men working in oral contraceptive production. Ketoconozole inhibits the enzymes required to produce hormones involved in sperm production and can immobilize sperm in seminal fluid. 

The progesiins are primarily used in oral contraceptive products and in hormone replaceinenl regimens for women. They are also used to treat several gynecological disorders dys-... 

Scheme 3.33). Addition of acetylene is notable for the mild reaction conditions. A good yield of 33-1 is obtained on simply bubbling acetylene into a solution of the steroid and potassium hydroxide. This product, dubbed mestranol, is a potent estrogen present in very small quantities in the great majority of oral contraceptive products. 

RATIO OF OBSERVED/EXPECTED NUMBERS OF REPORTS OF THROMBOSES WITH COMBINED TYPE ORAL CONTRACEPTION PRODUCTS... 

The first generation of the oral contraceptive products, introduced in around 1960,... 

Optoelectronics Optosil Oraflex Oragrafin Oral care products Oral contraceptives Oral formulations Oral polio virus vaccine Oral toxicity Oramec Orange... 

The two synthetic steroidal estrogens which have attained the greatest degree of therapeutic use are ethinyl estradiol [57-63-6] (EE) (5) and its 3-methyl ether, mestranol [72-33-3]((5). In contrast to the naturally occurring estrone derivatives, these acetylenic analogues are orally active and are the main estrogenic components of combination oral contraceptives (see Contraceptives) and certain estrogen replacement products. 

The 1950s and 1960s saw the development of orally active progestins based on the synthesis of steroids that lack the C19-angular methyl substituent (19-norsteroids). The commercial production of these compounds for the regulation of menstmal disorders began in 1957, and for oral contraception in 1960. 

L-Fohc acid is available as a crystalline dihydrate containing 8% water. Approximately 80% of the commercial production is consumed for feed enrichment in animal nutrition. FoHc acid is being offered by the pharmaceutical industry for therapeutic and prophylactic use (see Pharmaceuticals). Pharmacological doses of fohc acid are commonly used as a rescue dose during cancer chemotherapy, in women using oral contraceptives, and alcohoHcs. Several studies have provided evidence that multivitamins or foHc acid (0.8—4 mg/day) supplementation prevent the majority of neural tube defects (101). 

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. 

Reaction of estrone with a metal acetylide affords 17a-ethynyl-173-hydroxy-estradiol (etbynylestradiol, 30a EE). This compound is equipotent with estradiol by subcutaneous administration, but it is 15 to 20 times as active when administered orally. Ethynylation of the methyl ether of estradiol analogously affords mestranol (30b), It should be noted that the same factors apply in these reactions as in previously discussed reductions at 17 almost the sole products of these reactions are those which result from attack of reagent from the least hindered a side of the steroid. Ethynylestradiol and mestranol are of special commercial significance since the majority of the oral contraceptives now on sale incorporate one or the other of the compounds as the estrogenic component. 

In epidemiologic studies, all products containing less than 50 pg ethinyl estradiol per pill are summarized as low-dose oral contraceptives. The first generation of oral contraceptives includes products with 50 pg... 

Educating the Patient and Family The instructions for starting oral contraceptive therapy vary with the product used. Each product has detailed patient instruction sheets regarding starting oral contraceptive therapy, and the nurse reviews them with the... 

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions have assumed increasing importance following the discovery that certain steroids such as hydrocortisone have anti-inflammatory activity, whilst derivatives of the steroidal sex hormones are nsefiil as oral contraceptive agents. More recently, chiral inversion of non-steroidal anti-inflammatory dmgs (NS AIDs) has been demonstrated. 

Oral contraceptives are a valuable second-line treatment option for moderate to severe acne in female patients. Oral contraceptives decrease the production of androgens by the ovaries, which in turn leads to a decrease in sebum production.3,16... 

Adverse effects include nausea, weight gain, breast tenderness, and breakthrough bleeding. Oral contraceptives have also been associated with an increased incidence of thromboembolic disease, particularly in women who use tobacco products or have other risk factors for thromboembolism. The development of these complications is significantly reduced when low-dose estrogen formulations of oral contraceptives are used.3... 

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