Oral contraceptives hormonal combined,

PBS listing on medical grounds, economic factors including cost-effectiveness are taken into account, as required by the National Health Act, 1953. Fixed combination products are seldom considered suitable for inclusion in the PBS. Notable exceptions to this norm are oral contraceptives and combination hormone replacement therapies. Any new listing which has the potential to cost the PBS more than 10 million in the first full year of reimbursement must be approved by the Federal Cabinet. Otherwise, applications are approved by the Health Minister. 

Structures of steroids used as oral contraceptives. (A) Combination pills containing an estrogen -P progestin. (B) The progestin-only pill. (C) RU-486 or mifepristone, which can be utilized as an abortifacient. [Reproduced with permission from S. W. Norman and G. Litwack, Hormones, 2nd ed. San Diego Academic Press, 1997]. 

The estrogens, in combination with a progestin, are also used as oral contraceptives (Table 52-1). The uses of individual estrogens are given in the Summary Drug Table Female Hormones. The use of estrogens in the treatment of carcinoma is discussed in Chapter 55. 

Estrogens and progestins (combination oral contraceptives) are used as oral contraceptives. There are three types of estrogen and progestin combination oral contraceptives monophasic, biphasic, and triphasic. The monophasic oral contraceptives provide a fixed dose of estrogen and progestin throughout the cycle The biphasic and triphasic oral contraceptives deliver hormones similar to the levels naturally produced by the body (Table 52-1). 

Historically, the 1950s represented an important time in the control of human fertility. It was during that decade that the first combined oral contraceptives were developed. Shortly after the discovery that the exogenous administration of hormones such as progesterone successfully blocked ovulation, the use of hormonal steroids quickly became the most popular method of contraception worldwide. Specifically, combined oral contraceptives represent the most commonly used reversible form of contraception today and it is estimated that nearly 100 million women worldwide take oral contraceptives.1 Further, in the United States, it is estimated that at some time during their lives, more than 80% of women born since 1945 have used oral... 

Although suppression of FSH and LH is the primary mechanism by which combined oral contraceptives prevent ovulation, there are other mechanisms by which these hormones work to prevent pregnancy. Other mechanisms include reduced penetration of the egg by sperm, reduced implantation of fertilized eggs, thickening of cervical mucus to prevent sperm penetration into the upper genital tract, and slowed tubal motility, which may delay transport of sperm.1 Thus, in... 

Two synthetic estrogens are used in hormonal contraceptives in the United States, ethinyl estradiol (EE) and mestranol. Mestranol must be converted to EE in the liver to be active. It is approximately 50% less potent than EE. Most combined oral contraceptives (OCs) contain estrogen at doses of 20 to 50 meg of EE daily. The contraceptive ring produces one-half the serum concentration of EE derived from a 30-mcg OC. 

Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, because some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John s wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding while on oral contraceptives shortly after starting St. John s wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John s wort. 

Suggestive case histories raised at an early phase the notion of a possible correlation of oral contraceptives with endometrial cancer. Among cases of endometrial cancer there seemed to be an excess of users of oral contraceptives, particularly of the early high-dose estrogen type. With the virtual demise of these early products, the situation seems to have reversed a 1983 study from the Centers for Disease Control (CDC) in Atlanta showed that women who had used fixed combinations for oral contraception at some time in their lives had a relative risk of endometrial cancer of only 0.5 compared with never-users (112). The protective effect occurred only in women who had used oral contraception for at least 12 months, and lasted for at least 10 years after withdrawal. The WHO adopted the same view in 1988 in the light of multinational data (113). As in the case of hormonal replacement therapy, the protective effect seems to be due to the progestogen component. 

A meta-analysis of epidemiological studies of ovarian cancer showed a summary estimated relative risk of 0.64 for ever-use of combined oral contraceptives, implying a 36% reduction in ovarian cancer risk (130). This protective effect increased with increasing duration of oral contraceptive use and continued for at least 10 years after discontinuation. Although most of the oral contraceptives reported in these studies were older, higher-dose formulations, the Cancer and Steroid Hormone (CASH) study included users of tablets containing ethinylestradiol 35 pg or less, and this subgroup of women had a reduced risk of ovarian cancer (115). 

There is a possible association of oral contraceptives with erythema nodosum, which has been linked to the use of either estrogens or progestogens or a combination of the two however, probably neither hormone directly causes the condition but merely creates a fertile background for its generation by other antigens. 

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