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[the following text comes from "Estrogens and Progestins", "Contraceptive Agents" and "Agents Used to Treat Infertility", AMA Drug Evaluations, 5th Ed., AMA (American Medical Association), 1983; "Estrogens, Progestagens, Oral Contraceptives", Modern Pharmacology, Craig and Stitzel, Little, Brown, and Company, 1982]

Although these textbooks are dated, one may find it quite interesting and telling to learn of the amount of information that was available 20 years ago…

"In postmenopausal women treated with estrogen, changes in hepatic excretory function will result in greater cholesterol saturation in the bile, thus predisposing to gallstone formation. The risk of gallbladder surgery is increased 2.5 times in these women. Estrogens should not be given to patients with severe acute liver disease…It has been reported that the associated risk of developing angina pectoris almost doubled in women given postmenopausal estrogen therapy, although mortality was not increased (Ryan 1976; Gordon et al, 1978)…Estrogens are generally not administered to patients with migraine…Synthetic progestins should not be administered during pregnancy because of their teratogenic potential…The administration of any estrogen is contraindicated during pregnancy…There are reports of structural and functional abnormalities of the female reproductive tract resulting from in utero exposure to DES…Postpuberal girls whose mothers received DES during pregnancy should be examined yearly for early detection of abnormalities…in several studies, an increase in the risk of endometrial carcinoma has been associated with estrogen therapy in postmenopausal women…Endometrial cancer associated with estrogen therapy is usually an early stage malignancy. The latent period between estrogen administration and development of cancer is relatively short (three to six years) and the risk of cancer is reduced after an estrogen-free interval of two years (Hulka et al, 1980). These observations are consistent with the hypothesis that estrogen acts as a tumor promoter rather than as a carcinogen in endometrial carcinoma…" ["Estrogens and Progestins", pp. 943-946]

"Even after fertilization has occurred, pregnancy may be prevented with interceptive (‘morning after’) methods that alter the uterine environment to prevent nidation (e.g. High-dose estrogens, some OCs, intrauterine devices [IUDs]). [pp.957-8]

"It is important to distinguish between theoretical effectiveness and use effectiveness: The former measures efficacy after consistent correct usage and the latter after actual conditions of use. The higher failure rates shown by the use-effectiveness index may be due to improper technique (barrier methods), forgetting to take pills (OCs) or taking certain drugs concurrently…" [p.958, emphasis added]

"In general, OCs probably cause the widest variety of adverse effects, but complications associated with use of an IUD result in hospitalization more often and may be more likely to affect future fertility adversely…mortality is comparable with all methods until age 30, when the risk for smokers who take OCs increases. After age 35, the risk of death even among nonsmokers taking OCs may be greater than for patients relying on abortion or using IUDs…The risk of pelvic inflammatory disease (PID) is increased in all women who use IUDs, especially those having multiple sexual partners, those with a history of gonorrhea, and possibly younger women…PID may cause infertility…" [p. 959]

"Safety:…Concern was expressed that spermicides absorbed through the vaginal wall may have unidentified adverse effects on the woman, on a developing fetus (if the product is used inadvertently during pregnancy), or upon a nursing infant. In animals, nonoxynol 9 [now recognized to increase the risk of HIV infection] is absorbed transvaginally into the blood and is present in the serum of suckling neonates. In a retrospective study, the risk of certain congenital abnormalities (ie, limb-reduction deformities, neoplasms, hypospadias, chromosomal abnormalities) doubled and the incidence of spontaneous abortions among presumed users of vaginal spermicides may have increased (Jick et al, 1981)…A report of the Oxford Family Planning Association also suggested that the risk of congenital malformations associated with vaginal spermicide use may increase slightly, especially when conception resulted from contraceptive failure (Huggins et al, 1982)…It has been suggested that spermicides may cause non-lethal damage to sperm or have toxic effects on the ovum or blastocyst after absorption into the blood…it appears that any possible risk of congenital malformations associated with a vaginal spermicide would be very slight." [p.961]

"IUDs may not inhibit conception, but they do prevent implantation of the blastocyst by altering the biochemical milieu of the endometrium [early abortion; emphasis added]. The serum immunoglobulin level is elevated and may interfere with the normal immunologic tolerance that allows successful nidation. Sperm transport to the oviducts also is inhibited… The addition of copper [to the IUD] increases leukocytic infiltration, which enhances efficacy, and inhibits synthesis and liquefaction of endometrial mucus, which may prohibit proper contact between the blastocyst and endometrium [early abortion]. Prostaglandin production is greater with copper than with inert devices, and this probably stimulates the inflammatory reaction. Copper also may affect sperm directly, since motility is decreased. [Some IUDs release] small quantities (65 mcg daily) [of] progesterone continuously into the endometrial cavity; glandular atrophy and a chronic decidual reaction that is unfavorable for implantation results. Progesterone also may directly inhibit metabolism, capacitation and swimming speed of sperm…Normal cyclic function, including ovulation, continues as it does with other IUDs [i.e. causes early abortion; emphasis added]. [p.962]

Precautions for IUDs: "Perforation of the uterine wall and translocation of the device may occur at insertion. IUDs also have been reported to become embedded in the endometrium without perforation…If pregnancy occurs with an IUD in situ and the patient elects to complete the pregnancy, the risk of spontaneous first trimester abortion is increased (up to 50%)…Fatal septic abortions in patients wearing Dalkon Shields resulted in the withdrawal of this device from the U.S. market. Evidence suggests that the multifilament tail acted as a wick to carry pathogens into the uterine cavity, which usually is separated from the vaginal flora by the cervical mucus. However, other devices also have been associated with sepsis during pregnancy, and it is possible that any IUD with a string appendage may present some degree of risk. This would include all IUDs available commercially in the United States. The possibility of infection may be enhanced further if the IUD penetrates the endometrial surface…Allergy to copper has been reported infrequently with use of devices containing this metal. Patients with Wilson’s disease should not use copper-containi

ng IUDs. The incidence of pelvic inflammatory disease (PID) is increased two to ten times when IUDs are employed (Ory, 1978; Kaufman et al, 1980; A Vessey et al, 1981; Burkman, 1981)…If abdominal pain or tenderness, abnormal vaginal discharge, and fever occur, a diagnosis of PID should be considered…"[p.963] "…women who are at higher risk for PID (eg, history of PID, multiple sexual partners) are not good candidates for IUD use. The possibility of future infertility caused by PID should be considered and discussed with the patient before prescribing an IUD…Actinomyces-like organisms have been identified in cervical smears of patients who currently or recently used an IUD…Although patients are usually asymptomatic or have only mild clinical symptoms, endometritis, tubo-ovarian abscess, and, rarely, death have been reported… [With the use of IUDs] the likelihood that a pregnancy will be ectopic increases with duration of use (Vessey et al, 1979; emphasis added)…The increasing incidence of ectopic pregnancy with duration of use parallels and may be secondary to the increasing incidence of PID." [p.964]

Oral Contraceptives – "’Minipills’ contain a progestin only (norethindrone or norgestrel) [p.965]…Combination OCs inhibit ovulation through a negative feedback effect on the hypothalamus…The cervical mucus thickens (except with the most estrogenic preparations), which renders it unfavorable to penetration by sperm even if ovulation occurs. In addition, the quality of the endometrium may be unfavorable for nidation [i.e. early abortion, emphasis added], and tubal transport may be affected. Inhibition of ovulation is not a prominent feature of contraception with progestin-only minipills. [emphasis added] These agents cause formation of a thick cervical mucus that is relatively impenetrable to sperm; they may increase tubal transport time and also cause endometrial involution [early abortion]. [p.969]

Relative Potency: "The estrogen component of combination OCs marketed in the United States is either ethinyl estradiol or mestranol (3-methylether ethinyl estradiol). Ethinyl estradiol is 50% more potent than mestranol in animal assays, but…[C]omparison of the two hormones in doses of 50 mcg or more reveals little difference in their effects on the reproductive system, including endometrial histology, inhibition of ovulation, and gonadotropin secretion (Goldzieher et al, 1975)…Norgestrel is a recemic mixture of levonorgestrel and an inactive isomer having one-half the potency of levonorgestrel. Levonorgestrel and norgestrel have the strongest androgenic, anti-estrogenic, and progestational effects… [p. 970]

Precautions: "Patients should be warned that the risk of pregnancy is increased if pills are missed during the cycle…Patients taking OCs should be monitored regularly. Biannual blood pressure measurement and annual physical examination, including urinalysis, liver palpation, and breast and pelvic examinations, should be performedPatients also should be encouraged to examine their breasts monthly…The patient’s medical history must be examined carefully to identify possible contraindications. This is even more compelling with use of OCs than with other drugs…Most adverse effects associated with OCs are believed to be due to the estrogen component…The use of progestin-only products has been limited by lack of patient acceptance. The endometrium lacks the structural stability imparted by estrogen, and menstrual irregularities, ranging from intermenstrual spotting to amenorrhea, result. Anxiety about possible pregnancy also is common. When pregnancy occurs during minipill use, the ectopic/intrauterine ratio is higher than when other agents are employed. Common complaints associated with use of combination OCs include nausea, sometimes accompanied by vomiting; breast tenderness; and water retention…" [p.971]

Effects On Reproductive System: "Ovarian size is reduced since large follicles and corpora lutea are absent…The endometrium rapidly progresses from a proliferative to a secretory phase, and glandular atrophy and possibly stromal decidualization then occur, which accounts for decreased or even absent withdrawal bleeding. Regression of the endometrium after a few cycles may be a factor in short-term amenorrhea. Breakthrough bleeding and spotting are common during the first few cycles of use (particularly with low-dose preparations)…Cyclic menses usually resume within one to three months after cessation of OC therapy, although the interval from contraception to conception was reported to be longer in OC users than in women who used other contraceptive methods (Linn et al, 1982). Occasionally, failure of cyclicity persists for 6 to 12 months (postpill amenorrhea)…The quality and quantity of milk produced during lactation may be adversely affected by some OC formulations…The steroids are found in the milk with even low-dose preparations, and, although no adverse effects have been described with use of current formulations, their long-range effects on the nursing infant are not known…The progestin component is also found in milk, whereas natural progesterone is not (Committee on Drugs, American Academy of Pediatrics, 1981). [p.972]

Hepatic Effects: "The incidence of gallbladder disease and gallstones is increased when OCs are used; this is probably related to increased cholesterol concentrations in bile. Women who developed jaundice during pregnancy or nulliparous women with a genetic predisposition are at risk of developing cholestatic jaundice during [OC] therapy…Biopsies reveal cholestasis and, sometimes, minimal hepatocellular degeneration and necrosis. Upon cessation of OC use, jaundice and pruritus disappear and liver function tests return to normal without residual effects… Benign hepatic adenomas and focal nodular hyperplasia develop rarely during OC use…The relative risk of developing these tumors increases greatly after three years of OC use (Rooks et al, 1979). The tumors are potentially serious because of the danger of rupture…Palpation of the liver should be performed during every periodic examination of patients taking OCs…Cessation of OC use is mandatory and spontaneous regression usually occurs. Budd-Chiari syndrome also has been associated with oral contraceptive use (Lockhat et al, 1981). [emphasis added, p.973]

Carbohydrate, Lipid, and Protein Metabolism: "The effect of combination OCs on carbohydrate metabolism is complex. Utilization of glucose may be retarded with a compensatory increase in insulin secretion…Both the estrogen and progestin components probably affect carbohydrate metabolism, the latter apparently having the greater influence. Studies of selected OC preparations containing different progestins and progestins alone have shown that these agents all may elevate blood glucose and insulin levels…Patients who are diabetic only during pregnancy are particularly vulnerable to developing abnormal glucose tolerance with OCs. Also, patients who eventually develop diabetes (eg, those with a strong family history of the disease) may become clinically diabetic earlier than without the diabetogenic influence of OCs. [p. 973, emphasis added]

Cardiovascular and Hematologic Effects: "The preponderance of data from both prospective and retrospective studies reveals that the relative risk of developing idiopathic thromboembolic phenomena (including deep vein thrombosis and pulmonary embolism) is approximately 4 to 11 times greater, and the relative risk of superficial thrombosis is two to three times greater among women who use OCs. It appears that OC use causes about 80 new cases of deep vein thrombosis or pulmonary embolism per 100,000 previously healthy current OC users per year…The risk of post-operative venous thrombosis is doubled in OC users. Although the magnitude of the risk factor is small, the attributable risk, which is more meaningful clinically, is high (6.1/10,000 surgical procedures) because of the high incidence of this post-operative complication even without the influence of OCs (Stadel, 1981, part 1)…The risk of thromboembolic phenomena in OC users increases rapidly during the first month of use and declines at the same rate after discontinuation of treatment…OCs may alter the concentration of various clotting factors (increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin III)…In OC users the hematocrit and plasma fibrinogen levels are elevated, increasing blood viscosity (Lowe et al, 1980).These changes may be related causally to the greater risk of thromboembolic phenomena in patients taking OCs. The increased risk of deep vein thrombosis is believed to be due to the estrogen content of OCs…OCs should not be employed within one month before or after elective surgery or immediately postpartum because of the greater risk of thromboembolism at these times. Reports continue to substantiate the association of increased cardiovascular risk with OC useage, particularly in smokers and women over 35 years (Stadel, 1981, parts 1 and 2; Dalen and Hickler, 1981). The risk of death due to circulatory diseases, which were attributable primarily to ischemic heart disease and subarachnoid hemorrhage, is increased about fourfold in OC users (Royal College of General Practitioners, 1981). Although other studies have not found that past use of OCs affects the incidence of myocardial infarction, one large case-control study determined that past OC users between 40 and 49 years may be at continued risk of myocardial infarction (up to ten years after discontinuation) and that the risk increased with duration of use: 0 to five years use, no increased risk; five to nine years use, risk increased about twofold; ten or more years use, risk increased about threefold (Slone et al, 1981)…OC use appears to be an independent risk factor. However, the greatest influence of OCs is in their ability to multiply the effect of other risk factors (ie, age, smoking, hypertension, diabetes, obesity, hyperlipidemia)…The incidence of fatal and nonfatal stroke is increased in OC users. In current users, the risk of thrombotic stroke is increased about tenfold and that of hemorrhagic stroke is increased two- to threefold. An increased risk of subarachnoid hemorrhage also has been found in past OC users. Of the small percentage of fatal strokes among OC users, most are subarachnoid hemorrhages. Oral contraception, hypertension, and cigarette smoking are independent risk factors for stroke. The combination of OC use and hypertension increases the risk of both thrombotic and hemorrhagic stroke synergistically. Smoking also increases the risk of hemorrhagic stroke. The combination of cigarette smoking and OCs acts synergistically to increase the risk of subarachnoid hemorrhage to about 22 times that of women who do not smoke or use OCsIf cardiovascular risk persists in past OC users, it may be related to the effects of prolonged elevation of serum lipids and blood pressure and decreased glucose tolerance, which accelerate atherogenesis (Dalen and Hickler, 1981; Stadel, 1981, part 2)… Both the estrogen and progestin components of OCs may contribute to the increased risk of cardiovascular disease. Increases in clotting factors are usually attributed to estrogens…in one study, increasing the doses of progestins elevated the incidence of ischemic heart disease (norethindrone acetate) and strokes (norethindrone acetate and levonorgestrel) (Meade et al, 1980). If this observation is confirmed, it might be expected that other closely related progestins have similar effects. Because of the epidemiologic evidence that OCs increase the occurrence of cardiovascular disease, women with other risk factors…should be given OCs with caution and close monitoring…Cigarette smoking is a serious risk factor and women who smoke generally should not take OCs. The risk associated with cigarette smoking and OC use increases synergistically with age…women who use OCs are about three to six times more likely to develop hypertension than nonusers (see references in Dalen and Hickler, 1981). The probability of hypertension increases with duration of OC use and age and is most prominent in women over 35 years. The increase in blood pressure that normally occurs after age 40 apparently is accelerated in current OC users; women who are already hypertensive may experience a further rise…OCs have been associated with changes in the pattern of migraine headache…if migraine is first experienced after beginning OC medication or the frequency or intensity increases during treatment, therapy should be discontinued since they may be prodromal symptoms of stroke. [pp.974-6]

Teratogenicity: Sex hormones produce teratogenic effects on genital tissues. Large doses of diethylstilbestrol [DES] (and possibly other estrogens) produce defects in the reproductive tracts of both female and male offspring…Masculinization of female fetuses has occurred when some progestins (usually not those used in OC formulations) were taken during early pregnancy (eg, hormonal pregnancy tests, therapy for threatened abortion [i.e. EC, MAP])…because OCs may rarely cause such abnormalities, therapy should be discontinued as soon as pregnancy is confirmed." [pp. 976-7]

Carcinogenicity: "Women with a history of fibrocystic breast disease are considered to be at higher risk of breast cancer than those without prior benign breast disease…An increased incidence of endometrial cancer was observed in women who took the sequential type of OC (compared to those taking combined OCs), which may have been related to their relatively high estrogen content…since estrogen may stimulate the growth of existing endometrial cancer, OCs should not be prescribed for women with undiagnosed abnormal genital bleeding. Firm conclusions about the carcinogenicity of OCs are not yet possible because of the possible long latent period between the administration of a carcinogen and the development of cancer. [p. 977]

Miscellaneous Reactions: "…Hair loss and changes in hair growth and texture may be related to either the androgenic potency of the progestin component or a decrease in estrogen activity relative to previous endogenous levels. Rarely, a male pattern of hair growth may appear on the face and body or recession of temporal hair may occur on the scalp. Other manifestations of androgenicity include oily skin and scalp and acne…Some women (most commonly those with a previous history of a psychological disorder) may experience mood changes or develop depression while taking OCs… [p.977-8]

Drug Interactions: "There have been reports of pregnancies and breakthrough bleeding when OCs we

re taken with barbiturates, anticonvulsants, and particularly rifampin [Rigadin, Rimactane]…interactions with antibiotics, including ampicillin and tetracycline, resulting in decreased effectiveness of the OC (eg, breakthrough bleeding, pregnancy) have been reported…" [p.978]

Postcoital Contraception – "When coitus has occurred without contraceptive protection and pregnancy is not desired, interceptive (ie, at the post-fertilization stage) measures may eliminate unwanted pregnancy [early abortion] and avoid [surgical] abortion. Postcoital techniques are often referred to as "morning after" contraception. Various estrogen regiments or IUDs may be used for this purpose…Large doses are administered within 72 hours after unprotected midcycle sexual exposure. The estrogen may change the sequence of hormonal influences on the fallopian tubes, thereby disturbing the passage of the ovum. Estrogen also may alter the endometrial milieu and interfere with nidation [early abortion]. The effectiveness of ethinyl estradiol and conjugated estrogens as postcoital contraceptives were compared in a multicenter study. Ethinyl estradiol appeared to be more effective, but both drugs substantially reduced the number of pregnancies. With both preparations, the pregnancy rates were lower when treatment was instituted within 24 hours rather than 24 to 72 hours after coitus (Dixon et al, 1980). The patient who seeks postcoital contraception should understand that these high-dosage estrogen regimens are to be used infrequently or in emergencies (eg, rape, incest), for the presumed risk of serious side effects after frequently repeated large doses is unacceptable. In addition, nausea and vomiting are routinely a problem…Because of the teratogenic potential of estrogens, a pre-existing pregnancy must be ruled out before treatment is begun. DES (diethylstilbestrol) given during the first trimester of pregnancy is associated with a high incidence of vaginal adenosis and, rarely, adenocarcinoma in female offspring, as well as effects on the male urogenital tract…IUDs also are employed as an interceptive method [early abortion]…The IUD should be inserted within one day but may be inserted within several days after unprotected intercourse and left in place, if appropriate, for continuing contraception. [pp. 979-80]

Depot Preparations – "Several long-lasting depot preparations are under clinical investigation for use as contraceptives. These products are usually progestins but may contain both an estrogen and a progestin. One such preparation that is widely utilized throughout the world is depot medroxyprogesterone acetate (DMPA) (Depo-Provera). Intramuscular injection of 150 mg is given every three months, although the effect usually extends beyond this period. The drug is measurable in plasma for six to eight months after the last injection…The major mechanism of action of DMPA is inhibition of ovulation through suppression of the midcycle surge of LH secretion. Other contributing effects include thickening of cervical mucus and development of an atrophic endometrium that cannot support nidation [early abortion]. Fertility is delayed following contraceptive use of DMPA. For this reason, the drug is not recommended for young women whose contraceptive needs are to space children. Average time to conception after the last injection is about one year but may be as long as two and one-half years…" [p. 980, emphasis added]

Adverse Reactions (Depo-Provera): "Side effects include weight gain, depression, and headache. The most common problems are irregular menstrual cycles and spotting or amenorrhea, and most patients who discontinue therapy do so because of these complaints…the routine use of estrogens to "normalize" the menstrual cycle is not advocated. An atrophic endometrium develops progressively, and total amenorrhea is common 6 to 12 months after therapy is begun…DMPA (Depo-Provera) has glucocorticoid properties…Glucocorticoids are teratogenic in rabbits, as are large doses of DMPA…An increased risk of cervical carcinoma in situ also has been investigated…[OC users infected with HPV have a much greater risk of developing cervical cancer, 2003]… [DMPA] seems particularly justified in patients who are unable to use other forms of contraception, in those who are noncompliant in methods requiring cooperation, when estrogens are contraindicated…, and in intellectually or psychologically impaired patients. [pp. 980-1]

Conclusions: "The U.S. Food and Drug Administration (FDA) has refused to label the drug for contraception (it is commonly used in the United States to treat breast and endometrial cancer). The FDA concluded that the benefit/risk assessment differs among areas of the world and, with the advanced health care system in the United States, that the concerns of potential adverse effects outweigh the need for this contraceptive. ["Contraceptive Agents", AMA Drug Evaluations, 5th Ed., AMA, 1983, p.981]


["Agents Used to Treat Infertility", AMA Drug Evaluations, 5th, 1983]:

"Approximately 10% to 15% of couples who wish to have children experience some type of infertility that precludes pregnancy unless treatment is instituted; another 10% have less than the desired number of children (secondary infertility)…the male is the sole partner affected in about 30% of infertile couples…Even in the presence of two perfectly functioning reproductive systems, coitus must occur during the time when the fertile lives of the sperm (36 to 72 hours) and the ovum (24 hours) overlap. If coitus is spaced evenly two or more times a week, sperm capable of fertilization are almost always present in the woman’s reproductive tract… Endometriosis may be the single cause of infertility in 10% of infertile women and is a major factor in 25% to 40%. [pp.985-991]

["Estrogens, Progestagens, Oral Contraceptives", Modern Pharmacology, Craig and Stitzel, Little, Brown, and Company, 1982]

"The commercially available progestagens are primarily derivatives of either progesterone or testosterone. The latter are known as 19-norsteroids…The 19-norsteroids usually have more virilizing effects than progesterone derivatives…the 19-norsteroids are used primarily in oral contraceptive preparations…"[pp. 825-6] "Thus, biochemical effects produced by steroid hormones ultimately involve the regulation of intracellular protein synthesis in target tissues. [Estrogens "rapidly penetrate the cell membrane, largely by simple diffusion, and then interact with a cytoplasmic protein receptor…the estrogen-protein complex is transported to the nucleus" where it interacts with DNA and "results in…specific mRNA [for] ribosomal protein synthesis".] [pp. 829-831] "…Approximately 40 percent of postmenopausal women continue to have adequate estrogenic function and do not exhibit specific symptoms of hormone deficiency or associated metabolic effects. The use of endocrine therapy in patients with postmenopausal estrogen deficiency should be individualized…The lowest

possible effective dose is given for the shortest possible time (preferably less than 3 years)…[endometrial] biopsy should be repeated at 6 to 12 month intervals throughout the course of treatment…since only about 25 percent of postmenopausal women develop osteoporosis and since the effects of estrogen may be only temporary, it is difficult to justify the long-term administration of estrogens for this condition…The administration of diethylstilbestrol (DES) during pregnancy has resulted in an increased incidence of vaginal adenosis or adenocarcinoma in female offspring; congenital heart defects and lib-reduction defects also are possible. It is presumed that other estrogenic substances would have similar effects…In females, the cyclic administration of estrogen with or without a progestagen frequently relieves acne. There is a risk, however, of inducing amenorrhea in adolescent girls whose sexual development may still be incomplete. This is not acceptable therapy." [pp.831-832] "Worldwide use of oral contraceptives amounts to a yearly business of 350 million dollars, of which about 150 million is done in the United States [1982]. Although these compounds may be used for a variety of endocrine disorders, their most extensive use is in fertility control. Several therapeutic strategies have been followed for achieving this end. The sequential regimen was one in which an estrogen alone was given for 15 to 16 days, followed by 5 days of an estrogen-progestagen combination; these preparations have been withdrawn from the U.S. market because of a reportedly higher than normal incidence of endometrial carcinoma associated with its use. Another procedure involves small daily doses of a progestagen (the so-called mini-pill) such as norethindrone or dl-norgestrel…as mentioned earlier, progesterone has been incorporated into a T-shaped intrauterine device designed to release a constant amount of the hormone into the uterine cavity." [pp. 833-4]

Table 61-1. Estimated Annual Mortality Rate of Women from Myocardial Infarction (MI) by Use of Oral Contraceptives, Smoking Habits, and Age

  MI Mortality Rate (per 100,000)
  Women Aged
Women Aged
  Contraceptive Contraceptive
Smoking Habits Users Non-Users Users Non-Users
Smokers 10.2 2.6 62.0 15.9
Nonsmokers 1.8 1.2 10.7 7.4

Source: A.K. Jain, Mortality risk associated with the use of oral contraceptives, Stud. Fam. Plann. 8:3, 52, 1977. Reprinted with permission of The Population Council. [p. 835]

Estrogen & Male Feminization

Canadian scientists have found that water in a pond (created for this experiment) contaminated with estrogen from birth-control pills is having disastrous effects on male fish species. Studies have shown that male fish, from tadpoles to lake trout, are becoming "feminized", meaning that egg proteins are growing abnormally in their bodies, rendering them incapable of reproducing. In fact, the entire Fathead minnow population was nearly wiped out in this pond. "It's a feminization…it's enough to be concerned about what's going on in the bigger picture (from estrogen)", said karen Kidd, a research scientist at the Canadian Freshwater Institute.

Now the U.S. Geological Survey's Columbia Environmental Research Center is studying whether estrogen-contaminated water is affecting human males as well. As early as 1992, the Cincinnati Enquirer [11Sept92] reported that the sperm count in healthy males had dropped by half in the past 50 years, according to a global review of 61 studies involving nearly 15,000 men. Also, the risk of developing testicular cancer is up by 50% over the past 25 years, although neither have been attributed to estrogen contamination at this time.

Serious consideration should also be given to estrogen's effect on the male offspring of women who are on the birth control pill. Of the 10.4 million pill users in America, over 5 percent, or one-half million, get pregnant each year (i.e. the pill fails) according to the FDA. How does pill estrogen affect these children conceived during pill use?

We know today that women who were given Diethylstilbestrol (DES) in the 1950s, 60s and early 70s, have a 35% increased risk of developing breast cancer. Their daughters (and in some cases, their sons) have a higher rate of infertility and increased risk of unsuccessful pregnancies. A rare form of vaginal cancer in the daughters of women who were using DES has been attributed to this therapy…

[Compiled by Human Life Alliance, HLA Action News, Summer 2003 from reports in Couple to Couple League's MedWatch, the St. Paul Pioneer Press 28June2003; HLI Special Report, 1998, and Aging Today, May/June 2003]