Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Well over 100,000,000 women have used the combined oral contraceptive (OC) pill. As a result of the population explosion in the 1970s and 1980s, there will be almost one third more women in fertile age in the year 2000 than in 1991. In the developing world outside China, the total number of contraceptive users could double in roughly 10 years. China, the total number of contraceptive users could double in roughly 10 years. The pill has a low failure rate, but one study in Egypt found that 90% of women made errors in moving from one packet to the next. Similarly, a 60% error rate was found among users in Colombia. The vaginal ring delivers combined progestogen and estrogen through a silastic wall. The device can be left in place for 21 days out of 28, and such delivery would virtually eliminate the low risk of hepatocellular carcinoma among OC users. A vaginal progestogen ring is being tested. Over 700,000 women have used Norplant, the subdermal implant method with an effectiveness rate of 99%. Depo-provera and norethindrone enanthate injections last 2 to 3 months. The Progestasert IUD, containing 38 mg progesterone released at a rate of 65 mcg per day, is effective. Progesterone-releasing IUDs lasting from 3 to 5 years could complement subdermal implants. Ethinyl estradiol (205 mg) and diethylstilbestrol (25-50 mg) have both been used as postcoital agents taken within 36 hours for 5 consecutive days after unprotected intercourse. In more than 3000 cases there were 17 pregnancies (.05%). These regimens are replaced by giving combined oral contraceptive tables (e.g., .25 mg d-norgestrel and 50 mg ethinyl estradiol), taken 2 at a time and repeated 12 hours later, within 72 hours of unprotected intercourse. Epidemiological studies have confirmed that the use of the combined oral contraceptive for 3 to 5 years halves a woman's risk of ovarian or endometrial cancer, and the protection persists for 10 to 18 years after cessation of use.
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PMID:The future of hormonal contraception. 168 5

New trials of Norplant-R-2 were halted in August 1987 because the manufacturer of the silicone component used in the core of the contraceptive implant system discontinued its production. The Dow Corning Corporation decided to stop producing the elastomer used in the 2-rod Norplant-R-2 system after the UN Environmental Protection Agency (EPA) asked for further tests on a component of the catalyst used in the manufacturing process. The EPA request was based on reports that high doses of the substance, 2-ethylhexanoic acid, may cause hepatocellular carcinoma and congenital malformations in laboratory rodents. Dow based its decision on the fact that Elastomer 382 had a very low sales volume and conducting the additional tests would be costly. Its decision will not affect studies using Norplant-R-2. The Population Council has concluded that there is no increased health risk to current users of Norplant-R-2 from the 2-ethylhexanoic acid component and does not recommend removing Norplant-R-2. The US Food and Drug Administration (FDA) does not object to continuation of the clinical trials of Norplant-R-2 now underway. Until researchers can develop an alternate elastomer, all new preintroductory clinical trials of Norplant-R implants will use the Norplant-R capsules. The evidence regarding the toxicology of Elastomer 382 has been reviewed by a toxicology group consultation held by the World Health Organization (WHO) Special Programme for Research, Development and Research Training in Human Reproduction and the USFDA. The WHO review concluded that exposure of women to the maximum possible amount of 2-ethylhexanoic acid in Norplant-R-2 presented no human toxicological risk. When the Population Council evaluated the tests leading to the EPA's request for further studies, it found that in laboratory tests using compounds related to 2-ethylhexanoic acid, the lowest doses causing cancer in rats and mice were, by body weight, 13,000 times as much per day as the total potential amount of the component in Norplant-R-2. The increased incidence of malignant tumors in rats and mice receiving high doses of structurally-related compounds was confined to cancerous growths in liver cells. The Population Council intends to file an application with the USFDA in 1988 for regulatory approval for Norplant-R in the US.
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PMID:Norplant update. 1228 Sep 54