| 1. Title: Are low-dose oral contraceptives safer and better? [letter] Author: Hannaford PC Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1995 Jun;172(6):1948-9. Abstract: J. W. Goldzieher is concerned about the epidemiologic practice of placing oral contraceptives that contain 50 mcg of mestranol in the same category with those that contain 50 mcg of ethinyl estradiol. Such groupings compare older, "high-dose" pills with newer, "low-dose" pills; the 50-mcg pills contain either mestranol or ethinyl estradiol combined with high doses of progestogen, while those containing less than 50 mcg always contain ethinyl estradiol combined with lower doses of progestogen (including the newer levonorgestrel). In a nested case-control study of stroke from the Royal College of General Practitioners Oral Contraception Study, all 50-mcg oral contraceptives were placed together, but separation of data by specific type of estrogen produces a similar pattern of risk (Table 1). 84 cases and 335 controls were "never users" and had an adjusted odds ratio of 1.0. The adjusted odds ratios with 95% confidence intervals for users of mestranol or ethinyl estradiol at doses higher than, equal to, and lower than 50 mcg were 5.8 (1.2-22.8), 2.9 (1.7-5.0), and 0.6 (0.1-2.9), respectively. For users of mestranol at doses higher than and equal to 50 mcg they were 6.0 (1.5-23.8) and 3.4 (0.5-15.0), respectively. For those who used ethinyl estradiol at doses equal to or lower than 50 mcg they were 2.9 (1.7-5.2) and 0.6 (0.1-3.0), respectively. Secular trends within the cohort were taken into account by matching for age and time of event. These results provide the first evidence that the newer pills have a reduced risk of stroke because of their lower risk potential, rather than because doctors prescribe them to low-risk women. The limited available data concerning the newer pills and the protective effect of oral contraceptives against ovarian and endometrial cancer indicate the effect is not lost. Language: English Keywords: EPIDEMIOLOGIC METHODS | CASE CONTROL STUDIES | ERROR SOURCES | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, LOW-DOSE | MESTRANOL | ETHINYL ESTRADIOL | CEREBROVASCULAR EFFECTS | RISK ASSESSMENT | Research Methodology | Studies | Measurement | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Physiology | Biology | Evaluation Document Number: 105822 |
| 2. Title: Low-dose oral contraceptives are safer than high-dose pills [letter] Author: Lidegaard O Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1995 Jun;172(6):1950. Abstract: J. W. Goldzieher has three concerns regarding a 1990 Danish case-control study on the use of oral contraceptives and cerebral thromboembolism. First, Goldzieher believes the inclusion of transient cerebral ischemia and subarachnoid hemorrhage, neither of which have a thrombotic pathogenesis, confounds the diagnostic entity. Five diagnoses were included: ICD 432 to 436 (International Classification of Diseases, Eighth Revision). Subarachnoidal hemorrhage (ICD 430) is not among these. Cerebral apoplexia (ICD 436) includes 80-85% of thrombotic cases (known from autopsy cases); the inclusion of 98 patients with these unspecified strokes, including cerebral hemorrhages, may have underestimated the calculated odds ratios marginally. Since the calculated odds ratios for transient cerebral ischemia and for ischemic strokes were identical, the inclusion of transient cerebral ischemic attacks in the Danish study did not influence the calculated odds ratios. Second, Goldzieher was concerned that a subject was classified as a nonuser of oral contraceptives if she had not used them for greater than or equal to 1 day preceding the cerebral episode. Women in the study were considered users if they used oral contraceptives at the time of thrombosis, and nonusers if they did not. Third, Goldzieher claims the overriding problem with forming conclusions from the study, in regard to dose relationships, is the failure of the authors to understand that ethinyl estradiol and mestranol are not bioequivalent. During the study period (1985-1990) in Denmark, 50 mcg of mestranol was found in two brands of oral contraceptives. These brands accounted for 3% of sales and were included in the group of middle estrogen (50 mcg) pills on the assumption that all mestranol is converted to ethinyl estradiol. If some mestranol was eliminated without conversion, the middle estrogens included a small number of miniestrogen (30-40 mcg) preparations. In light of their small share of the market, this bias does not influence the calculated risks substantially. The difference in risk would have been greater if they had been included with the miniestrogen group; the safety of the miniestrogen group may be underestimated. Many investigators have found a consistent dose-response relationship between estrogen dose and risk of thrombosis. Language: English Keywords: EPIDEMIOLOGIC METHODS | CASE CONTROL STUDIES | ERROR SOURCES | ORAL CONTRACEPTIVES, LOW-DOSE | MESTRANOL | ETHINYL ESTRADIOL | CEREBROVASCULAR EFFECTS | RISK ASSESSMENT | Research Methodology | Studies | Measurement | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Physiology | Biology | Evaluation Document Number: 105821 |
| 3. Title: Pharmacology of contraceptive steroids. Author: Goldzieher JW Source: In: Contraception, edited by Donna Shoupe, Florence P. Haseltine. New York, New York, Springer-Verlag, 1993. :17-24. (Clinical Perspectives in Obstetrics and Gynecology) Abstract: This consideration of the pharmacology of contraceptive steroids begins with a review of the accidental addition of 17 alpha-ethynyl estrogens to oral contraceptives (OCs) which resulted from the 15% contamination with mestranol of the first 19-norprogestins manufactured. The mestranol caused nausea and other side effects, but, when it was withdrawn, breakthrough bleeding occurred, so it was reintroduced in a smaller dose which was eventually reduced to 20 mcg per tablet. Today, all except progestin-only OCs contain either ethinyl estradiol (EE) or mestranol (MEE) which is absorbed rapidly from the stomach. To illustrate a discussion of the range of pharmacokinetic values for single-dose EE administration, the values reported in the literature are displayed in tabular form. The bioavailability yields for EE and MEE are reported as having wide interindividual and intraindividual variations. It is pointed out that a confusing bioequivalence problem exists because most epidemiologists are unaware that 50 mcg of MEE is equivalent to 35 mcg of EE in an OC. Ethnic differences in enzyme activities of the liver, and possibly the intestine, may account for the differences found in the different proportions of sulfate and glucuronide conjugates which appear among populations in studies of urinary EE metabolites. Different degrees of oxidative metabolism are also seen from country to country. A general discussion continues about the biological activities of progestational compounds which are presented in tabular form. Bioassays have been found for all of them, but some may be irrelevant to oral contraceptive formulation. The complexity of these various biological activities is mentioned as is the goal for new OCs (to be metabolically neutral and to have no effect on carbohydrate metabolism, plasma lipid levels, etc.). The general discussion continues with comments on the complexity of receptor affinity and the potency of progestational compounds and how this is properly defined. Rozenbaum's primer of steroid chemical structure is said to be useful, and norethindrone and levonorgestrel are defined as the reference compounds for the 2 classes of progestins. Finally, the pharmacokinetics and metabolism of norethindrone, levonorgestrel, gestodene, desogestrel, and norgestimate are discussed. Language: English Keywords: ORAL CONTRACEPTIVES | METABOLIC EFFECTS | ESTROGENS | ETHINYL ESTRADIOL | MESTRANOL | NORETHINDRONE | LEVONORGESTREL | GESTODENE | DESOGESTREL | NORGESTIMATE | Contraceptive Methods | Contraception | Family Planning | Physiology | Biology | Hormones | Endocrine System | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin Document Number: 098292 |
| 4. Title: Consistent lack of association between breast cancer and oral contraceptives using either hospital or neighborhood controls. Author: Morabia A; Szklo M; Stewart W; Schuman L; Thomas DB Source: PREVENTIVE MEDICINE. 1993 Mar;22(2):178-86. Abstract: Between 1973 and 1975, in Maryland, the Baltimore Women's Health Study compared data on less than 60-year-old White women with a first primary breast cancer in Baltimore City and Baltimore County with data on hospital and neighborhood controls to determine whether the previous observed association between breast cancer and oral contraceptive (OC) use varied according to the type of control group. All OC formulations, except Lestrin, had more than 49 mcg of ethinyl estradiol or mestranol. Breast cancer cases were more likely to have more education, no children, a first birth at age 25 or older, a breast lump, or a family history of breast cancer. The relative odds (RO) of breast cancer for ever users of OCs was 1 for hospital controls and 0.8 for neighborhood controls (unmatched analysis). The RO did not increase proportionately with duration of OC use, but the RO for women who had used OCs for at least 24 months was high (1.4 vs. 0.4 for 12-23 months and 0.6 for 1-11 months). Around 50% of all OC users used high progestogen potency OCs, but no association between breast cancer and progestogen potency existed (RO = 1). The matched analysis revealed that the RO of breast cancer for ever users of OCs was 0.9 when the researchers used hospital controls, 1.1 for neighborhood controls, and 0.9 for matched triplets (1 case, 1 hospital control, and 1 neighborhood control). The lack of association of both the unmatched and matched analyses remained the same regardless of control group. The findings of no association between OC use and breast cancer are consistent with those of the CASH study and the study of McPherson et al. These findings are even more encouraging since the strength and potency of OCs have fallen with time. Yet we cannot presume these findings would be the same in nonWhite women, women who used OCs before their first full-term birth, or those who used OCs for more than 2 years. Language: English Keywords: UNITED STATES OF AMERICA | MARYLAND | METHODOLOGICAL STUDIES | CASE CONTROL STUDIES | ORAL CONTRACEPTIVES, COMBINED | BREAST CANCER | RISK FACTORS | CONTRACEPTIVE AGENTS, PROGESTIN | WHITES | TIME FACTORS | AGE FACTORS | MESTRANOL | ETHINYL ESTRADIOL | RESEARCH METHODOLOGY | DATA ANALYSIS | ADMINISTRATION AND DOSAGE | WOMEN | SIDE EFFECTS | EPIDEMIOLOGIC METHODS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | Developed Countries | North America | Americas | Studies | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Biology | Contraceptive Agents, Female | Contraceptive Agents | Ethnic Groups | Cultural Background | Population Characteristics | Demographic Factors | Population | Population Dynamics | Contraceptive Agents, Estrogen | Drugs | Treatment Document Number: 092316 |
| 5. Title: Oral contraceptives. Author: Chaudhuri SK Source: In: Practice of fertility control: a comprehensive textbook. 3rd ed., [edited by] S.K. Chaudhuri. New Delhi, India, B.I. Churchill Livingstone, 1992. :95-119. Abstract: Oral contraceptive (OC) failure rates are < 1% for combined and multiphasic OCs and 3-10% for minipills. Combined OCs are classified by the estrogen component: ethinyl estradiol (EE) or mestranol. EE combined OCs include low dose (< .05 mg ethinyl estradiol) and standard dose (.05 mg ethinyl estradiol). The progestogen component of combined OCs is either the norethisterone group or the norgestrel/desogestrel group. They prevent pregnancy by suppressing ovulation, inhibiting implantation, and making cervical mucus unable to allow penetration of sperm. The multiphasic OCs (biphasic and triphasic OCs) have fewer side effects than combined OCs. Their main way of preventing pregnancy is ovulation suppression. They also contain EE and a progestogen component, but during the cycle, the hormone dose changes. The progestogen only OCs (minipills) contain either 0.3 mg norethisterone, 0.07 mg norgestrel, 0.5 m ethynodiol diacetate, or 0.5 mg lynestrenol. They change the endometrium thereby preventing implantation of the fertilized ovum. They are best for women who have or are at risk of thromboembolism as well as for lactating women. Minipills are more apt to fail and cause breakthrough and irregular bleeding than the multiphasic and combined OCs. Women must take 1 pill every day of their menstrual cycle, except those that have a 7 day gap during menstruation OCs stabilizes the menstrual cycle and eliminates most menstrual disorders. They protect against endometrial and ovarial cancer. OCs even protect against pelvic inflammatory diseases, anemia, malnutrition, and endometriosis. Some minor side effects include nausea, vomiting appetite reduction, headache, vaginal discharge, and breast changes. Major side effects are cardiovascular diseases: increased risk of breast, cervical, and liver cancer; worsening of diabetes mellitus; and liver and gall bladder effects. Women older than 35 who smoke should not use OCs. Barbiturates, sulphonamides, rifampicin, and anticonvulsant drugs adversely affect OC effectiveness. Language: English Keywords: DEVELOPED COUNTRIES | DEVELOPING COUNTRIES | HISTORICAL REVIEW | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, CONTRAINDICATIONS | ORAL CONTRACEPTIVES, SIDE EFFECTS | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | LOW-DOSE PROGESTINS | ETHINYL ESTRADIOL | MESTRANOL | NORETHINDRONE | NORGESTREL | CONTRACEPTIVE EFFECTIVENESS | CONTRACEPTION CONTINUATION | ENDOMETRIAL CANCER | OVARIAN CANCER | NEOPLASMS, BENIGN | CARDIOVASCULAR EFFECTS | BREAST CANCER | CERVICAL CANCER | DIABETES | LIVER NEOPLASMS | HEPATIC EFFECTS | LACTATION | DRUG INTERACTIONS | PREVENTION AND CONTROL | CONTRAINDICATIONS | SIDE EFFECTS | Contraceptive Methods | Contraception | Family Planning | Contraceptive Safety | Safety | Public Health | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Contraceptive Usage | Cancer | Neoplasms | Diseases | Physiology | Biology | Maternal Physiology | Drugs | Treatment Document Number: 079631 |
| 6. Title: Oral contraceptives and breast cancer risk in Denmark. Author: Ewertz M Source: EUROPEAN JOURNAL OF CANCER. 1992;28A(6-7):1176-81. Abstract: In Denmark, researchers compared data on 203 <40-year old women diagnosed with breast cancer between March 1983 and August 1984 with data on 212 <40-year old women with no breast cancer to examine the effect of oral contraceptives (OCs) on breast cancer risk. They did the same analysis with 40-59 year old women (856 cases and 778 controls) between March 1983 and February 1984. No association existed between OC use and Breast cancer risk among the 40-59 year old women. There was no increased breast cancer risk associated with longterm OC use (>4 years) in <40-year old women or before 1st birth. Yet there was an increased risk for short-term use in <40-year old women (age adjusted relative risk [RR]=1.56) or before 1st child birth (RR=1.5 for 2-4 years and 2.7 for <2 years). Recall bias may have accounted for this increased risk. 40-59 year old women living in rural areas had a significantly higher RR of breast cancer than those living in urban areas (1.22; p<.01). Even though no evidence indicated selection bias, it still may have accounted for this increased risk. The largest RR of breast cancer occurred among women who used OCs with at least 50 mcg of mestranol for =or> 5 years (2.05). Major obstacles of this study, like that of other studies, were the get number of OC brands marketed, e.g., 64, and recall bias in terms of brand used and duration. Nevertheless this study did not detect an overall association between OC use and breast cancer risk. It did reveal, however, that longterm use of high-dose estrogen OCs may have elevated the breast cancer risk. Language: English Keywords: DENMARK | METHODOLOGICAL STUDIES | CASE CONTROL STUDIES | ORAL CONTRACEPTIVES, SIDE EFFECTS | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, PROGESTIN | MESTRANOL | BREAST CANCER | AGE FACTORS | BIAS | OBSTACLES | RISK FACTORS | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Europe, Northern | Europe | Developed Countries | Studies | Research Methodology | Contraceptive Safety | Safety | Public Health | Health | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Cancer | Neoplasms | Diseases | Population Characteristics | Demographic Factors | Population | Error Sources | Measurement | Organization and Administration | Biology | Treatment Document Number: 076634 |
| 7. Title: [P-pills and risk of breast cancer. A review of studies published 1970-1990] P-piller og risiko for cancer mammae. En oversigt over undersogelser publiceret 1970-1990. Author: Glud E; Ewertz M Source: UGESKRIFT FOR LAEGER. 1992 Jan 27;154(5):260-6. Abstract: 5 cohort studies investigated the connection between oral contraceptives (OCs) and mammary cancer (MC). 2 English studies followed up 18,000 women for 20 years; the 2 cohorts had 200 cases of MC among them. 2 American studies analyzed 120,000 nurses with 1800 cases of MC among them for 6 and 10 years when OCs had been in use for over 10 years. No connection was found between OCs and MC. In 1 English study a significant increased relative risk (RR) of 5.8% was found among women who had had a pregnancy before the diagnosis of MC. Nulliparas or multiparas did not have an increased risk. Among women aged 30-44 there was also increased risk with an RR of 3.3. A total of 33 case controls studies evaluated this connection: 18 hospital-based ones, 15 population-based ones, and 1 involving both. Most subjects were under age 45. 4 of the hospital studies indicated a significantly increased risk of MC with the use of OCs: RR of 1.1-2. Increased risk of MC was found among women under 33 when diagnoses using OCs for 5 under years: RR of 1.5 in 4 years of use. In contrast, another study reported RR of .4 for OC use of 5 years among women under 50. Among women under 45 with 5-9 years of OC use RR was 1.2-1.9 in 6 studies. RR was significantly increased (1.2-4.1) in OC use of 10 years or longer. A 1981 study found increased risk (not confirmed by others) for MC among women who had used OCs before the birth of their 1st child. In 4 studies increased risk was found (RR of 1.4-3.5) with the OC use of 8 years or longer before 1st birth. The risk of MC was increased with the use of mestranol-containing OCs in 1 study not corroborated by others. Doses of <50 mcg of estrogen and >50 mcg produced RR of 1.4 and 1.5, respectively. There seems to be an increased risk of MC with OC use of 5-10 years before age 45 or before 1st pregnancy. Language: Danish Keywords: ORAL CONTRACEPTIVES | BREAST CANCER | FOLLOW-UP STUDIES | CASE CONTROL STUDIES | RISK ASSESSMENT | MESTRANOL | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Contraceptive Methods | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Studies | Research Methodology | Evaluation | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Treatment | Demographic Factors | Population Document Number: 072388 |
| 8. Title: [Development of Hungarian oral contraceptives] A magyar fogamzasgatlo tablettak korszerusodese. Author: Seregely G Source: ACTA PHARMACEUTICA HUNGARICA. 1992 Nov;62(6):278-83. Abstract: The Hungarian pharmaceutical company Gedeon Richter has been in the front-line of manufacturing hormonal preparations in Europe in its 91 years of history, because between the 2 world wars it distributed several organotherapeutic drugs. 10 years after Enovid, the first American oral contraceptive (OC), was introduced, the Hungarian Infecundin was introduced containing 2.5 mg of norethynodrel and .1 mg of mestranol. When studies indicated that high estrogen levels resulted in liver damage and produced thromboembolic sequelae, no more than .075 mg of estrogen was mandated by the World Health Organization. In 1970 the Hungarian product Bisecurin, containing 1 mg of ethynodiol diacetate and .05 mg of ethinyl estradiol (EE), was developed. Another OC, Continuin, was developed for women susceptible to thrombosis and for lactating mothers in 1974; it had only gestagen: .5 mg of ethynodiol diacetate. The next OC, Ovidon, contained .25 mg of levonorgestrel (LNG) and .05 mg of EE. Low-dose pills followed: Rigevidon with .15 mg of LNG and .03 mg of EE, which became very popular among young nulliparous women. Postinor, a post-coital OC with .75 mg of LNG, was developed for women who had occasional sex. Phasic OCs prevent endometrial and uterine atrophy: the 2-phase Anteovin (11+10 days) and the 3-phase Tri-Regol (6+5+10 days). Rigevidon and Anteovin are the most popular. In 1991 a total of 2,043,846 Anteovin packets (or cycles) were used in addition to 1,558,785 Rigevidon packets and 521,220 Tri-Regol packets. Results of a multicenter clinical trial with 1891 women taking Tri-Regol during 9596 menstrual cycles indicated only 1 pregnancy, and 34 (1.8%) women discontinued because of side effects. Spotting occurred only in 5%, and subjective side effects included headache, mammary tension, and nausea. Language: Hungarian Keywords: HUNGARY | HISTORICAL REVIEW | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, LOW-DOSE | ORAL CONTRACEPTIVES, PHASIC | NORETHYNODREL | MESTRANOL | THROMBOEMBOLISM | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | LEVONORGESTREL | CONTRACEPTIVE EFFECTIVENESS | Developing Countries | Europe, Central | Europe | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Embolism | Vascular Diseases | Diseases Document Number: 090424 |
| 9. Title: Introduction -- thirty years of the pill. Author: Roland M Source: INTERNATIONAL JOURNAL OF FERTILITY. 1991;36 Suppl 3:8-9. Abstract: The editor of the International Journal of Fertility, gave a historical survey of research and development of oral contraceptives (OCs) at the Pan American Conference on Fertility and Sterility. G.D. Searle and Co. hosted the first symposium on 19-nor progestational steroids in January 1957. 2 other steroids concurrently developed were norethynodrel also called Enovid (G.D. Searle) and norethindrone (Parke-Davis and Syntex). As part of the pilot studies, the editor, who was a medical researcher, examined sequential endometrial biopsies (5-day intervals) in the same cycle from women with normal ovulatory cycles and from those with anovulatory cycles. 1 22-year-old woman had a bilateral oophorectomy at age 19. The various steroids caused morphologic changes in the endometrium. Some researchers found that Enovid caused estrogenic effects on the endometrium and later learned that synthesis of norethynodrel resulted in traces of mestranol. It would have been too costly to remove it. Researchers decided to keep the mestranol component in Enovid since it prevents breakthrough bleeding and prepares the endometrium for the progestogen. They even added 0.1 mg more mestranol to the formulation of Enovid. Eventually, researchers studied other combinations of progestogens and estrogens, e.g., norgestrel and ethinyl estradiol. This early research laid the ground work for development of the long-acting contraceptive implant, Norplant, which contains levonorgestrel. Increased use of such longer acting hormonal contraceptives should result in a considerable fall in use of induced abortion as a birth control method. Language: English Keywords: CONFERENCES AND CONGRESSES | HISTORICAL REVIEW | ORAL CONTRACEPTIVES | RESEARCH AND DEVELOPMENT | PROGESTERONE | NORETHYNODREL | NORETHINDRONE | NORGESTREL | MESTRANOL | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES, COMBINED | ENDOMETRIAL EFFECTS | HISTOLOGY | CONTRACEPTIVE IMPLANTS | LEVONORGESTREL | Contraceptive Methods | Contraception | Family Planning | Technology | Economic Factors | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System Document Number: 080120 |
| 10. Title: Hormonal content of combined oral contraceptives in relation to the reduced risk of endometrial carcinoma. Author: Rosenblatt KA; Thomas DB Source: INTERNATIONAL JOURNAL OF CANCER. 1991 Dec 2;49(6):870-4. Abstract: A retrospective case-control study of endometrial cancer and use of combined oral contraceptives by formulation, including 220 cases and 1537 age- and hospital-matched controls from 9 centers in 7 countries, conducted by WHO found reduced risk with high-progestin dose pills. Women born after 1925-1930, with histologically diagnosed endometrial carcinoma, were matched with up to 8 controls taken from patients admitted with 24 hours of diagnosis, who had no contraindication to taking orals. The histologic type of endometrial carcinoma in cases were adenocarcinomas 88.2%, adenosquamous 7.3%, clear-cell 1.8%, undifferentiated 1.8%, and squamous 0.9%. Oral contraceptives were classified by progestogen activity according to the subnuclear vacuolization scheme of Dickey, and pills were considered low-dose estrogen is they contained <50 mcg ethinyl estradiol for <100 mestranol. Odds ratios, calculated by conditional logistic regression, were 0.00 (95% confidence limits 0.00-1.08) for high dose progestin/low dose estrogen pills, and 1.10 (0.13-9.06) for low progestin/high estrogen pills. Odds ratios for high estrogen/high progestin, and low estrogen/low progestin were in between, 0.15 and 0.59. The odds ratio for all high-dose progestin pills combined was 0.21, and lasted over 10 years, even if a woman had taken them for <2 years. Protection against endometrial cancer for those who took low-dose progestin pills was not apparent until >2 years of use, and lasted <10 years. 2 of 3 previous studies on oral contraceptives by formulation and endometrial cancer obtained similar results. Language: English Keywords: AUSTRALIA | CHILE | CHINA | ISRAEL | MEXICO | PHILIPPINES | THAILAND | STATISTICAL STUDIES | ENDOMETRIAL CANCER | RISK ASSESSMENT | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTIVE AGENTS, ESTROGEN | MESTRANOL | ETHINYL ESTRADIOL | ETHYNODIOL DIACETATE | NORETHINDRONE | LYNESTRENOL | MEDROXYPROGESTERONE ACETATE | NORETHINDRONE ACETATE | NORGESTREL | MEGESTROL ACETATE | MULTIVARIATE ANALYSIS | CASE CONTROL STUDIES | HOSPITALS | Developed Countries | Oceania | South America, Southern | South America | Latin America | Americas | Developing Countries | Asia, Eastern | Asia | Middle East | North America | Asia, Southeastern | Studies | Research Methodology | Cancer | Neoplasms | Diseases | Evaluation | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Data Analysis | Health Facilities | Delivery of Health Care | Health Document Number: 071184 |
| 11. Peer Reviewed Title: [Effects of Sequostat as compared to Sequenz-Ovosiston on selected metabolic parameters] Wirkung von Sequostat im Vergleich zu Sequenz-Ovosiston auf ausgewahlte Parameter des Stoffwechsels. Author: Etzrodt R; Klinger G; Carol W Source: ZENTRALBLATT FUR GYNAKOLOGIE. 1990;112(8):489-96. Abstract: The effects of 2 sequential oral contraceptives (OCs), Sequostat (6 days ethinyl estradiol 0.05 mg, 15 days ethinyl estradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequenz-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg), on triglycerides, total cholesterol, HDL and LDL cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase, and antithrombin III were studied in 2 groups of women (total=75 women). Investigations were performed prior to the hormonal intake and after treatment for 3, 6, and 12 months. SIgnificant but minimal changes were noted across all parameters; however, Sequenz-Ovosiston exerted less of an effect on glucose tolerance. A significant increase in HDL cholesterol and a reduction in the LDL/HDL cholesterol relation was demonstrated during the 1st 6 months, which was the result of estrogen dominance in the OCs. (author's modified) (summaries in GER, ENG) Language: German Keywords: ORAL CONTRACEPTIVES, PHASIC | ETHINYL ESTRADIOL | NORETHINDRONE ACETATE | MESTRANOL | CHLORMADINONE ACETATE | LIPID METABOLIC EFFECTS | CHOLESTEROL | GLUCOSE TOLERANCE TEST | PLASMA PROTEIN BINDING CAPACITY | SIDE EFFECTS | CHANGES | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Oral Contraceptives, Combined | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Norethindrone | Contraceptive Agents, Progestin | Lipids | Physiology | Biology | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Hemic System | Treatment | Social Change | Contraceptive Safety | Safety | Public Health | Health | Demographic Factors | Population Document Number: 064403 |
| 12. Title: Cytogenetic study of blood in women who had used oral contraceptives. Author: Fridrichova I Source: NEOPLASMA. 1990;37(5):545-53. Abstract: Health professionals took 87 peripheral blood samples from 31 20-25 year old students from Bratislava, Czechoslovakia who had never used any oral contraceptive (OC) before to observe the cytogenic effects of OC. They got the 2nd sample 1 month after 24 women began using an OC and the 3rd sample 2 months after 7 began using it. The 3rd sample was taken after 3 months and only 25 women were still using an OC. Before OC use, they observed only 6.005% of all cells being abnormal. Most of these abnormal cells had chromatid gaps (4.3%) and breaks (1.11%). No matter what OC was used, the percentage of abnormal cells after 1, 2 and 3 months stood at 8.99%, 11%, and 12.12%. respectively. Again chromatid gaps and breaks were responsible for most of the abnormalities, and they occurred more often (5.68 and 1.77; 8.57 and 1.86; 7.6 and 2.28 respectively). The researchers also saw more complicated rearrangements of chromosomes, e.g., deletions, rings, and dicentrics, after OC use. no significant difference existed between the occurrence of hypodiploidy cells before OC use (3.44%) and after OC use (3.64%). Using Poisson's distribution, the researchers learned that a highly significant difference occurred in the total number of structural abnormalities between the controls and the affected variants (4.18, 3.12 and 7.36 after 1, 2, and 3 months) and the affected cells after 1 and 3 months (3.66). Further, there was a statistical difference between the controls and samples after 1 and 3 months (2.36, 4.40). In addition, after 3 months of OC use only a slow increase in the genetic effect on chromosomes can be expected. The researchers recommended that young women should use OCs cautiously before conceiving a child since OCs may also cause chromosomal abnormalities in gametes. Language: English Keywords: CZECHOSLOVAKIA | CYTOLOGY | ORAL CONTRACEPTIVES | CHROMOSOME ABNORMALITIES | HEMATOLOGIC TESTS | NORGESTREL | MESTRANOL | NORETHINDRONE ACETATE | ESTRADIOL | Developing Countries | Europe, Central | Europe | Biology | Contraceptive Methods | Contraception | Family Planning | Neonatal Diseases and Abnormalities | Diseases | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Norethindrone | Estrogens | Hormones | Endocrine System | Physiology Document Number: 065667 |
| 13. Peer Reviewed Title: Pharmacokinetics of ethinyl estradiol and mestranol. Author: Goldzieher JW; Brody SA Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1990 Dec;163(6 Pt 2):2114-9. Abstract: Pharmacokinetically, a 50 mcg oral dose of mestranol (which itself is inactive), is bioequivalent to a 35 mcg dose of ethinyl estradiol. Physiologically, mestranol ranges from 50-100% of the activity of ethinyl estradiol, depending on the endpoint chosen. Compounds such as these, which are metabolized with a 1st pass effect and are enterohepatically recirculated, demonstrate large interindividual and intraindividual variability in their pharmacokinetics. Thus, a given dose of ethinyl estradiol in 1 person may produce an effect equivalent to a substantially larger (or smaller) does in another person. This wide variability confounds efforts to establish tight dose-response relationships, a point rarely considered in clinical or epidemiologic studies of these compounds. The circulating levels of ethinyl estradiol sulfates may be higher than those of free ethinyl itself. It has been thought that these sulfates represent a reservoir of ethinyl estradiol. The author's studies show that this idea is untenable because the 1.2-life of the sulfates is not long enough for such an effect. Differences in the pharmacokinetics of ethinyl estradiol and mestranol have been observed in studies of various populations. The reality of these group differences is affirmed by analyses of urinary metabolite patterns. (author's) Language: English Keywords: UNITED STATES OF AMERICA | SRI LANKA | NIGERIA | ETHINYL ESTRADIOL | MESTRANOL | ETHNIC GROUPS | LABORATORY EXAMINATIONS AND DIAGNOSES | COMPARATIVE STUDIES | CROSS-CULTURAL COMPARISONS | ANALYSIS | Developed Countries | North America | Americas | Asia, Southern | Asia | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Cultural Background | Population Characteristics | Demographic Factors | Population | Examinations and Diagnoses | Studies | Research Methodology Document Number: 064663 |
| 14. Title: Selected aspects of the pharmacokinetics and metabolism of ethinyl estrogens and their clinical implications. Author: Goldzieher JW Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1990 Jul;163(1 Pt 2):318-22. Abstract: The variability in the pharmacokinetics of ethinyl estradiol (EE) is pronounced, especially regarding such parameters as area under the curve, half-life, and time to peak. This variability shows up in different populations, different individuals, or in the same individual, and can even exceed the differences between low dose (35 mcg) and high- dose (50 mcg) formulations. 50 mcg of mestranol and 35 mcg of ethinyl estradiol both produce similar plasma EE levels. Qualitative differences in the oxidative metabolites of estrogens may be of significance with respect to oncogenic potential. The pharmacokinetic differences of EE whether caused by dietary, ethnic, or other factors are not merely differences in gastric absorption or renal excretion. Studies on kinetics and bioavailability showed that after oral administration of EE 3-sulfate only about 20% appeared as free EE in the blood, while EE 17-sulfate produced about half this amount. Individual variation showed a large spread both for plasma total EE sulfate levels and free EE. The pharmacokinetics of three 1 mg norethindrone/35 mcg EE and three 1 mg norethindrone/50 mcg mestranol formulations were analyzed and the mean values, standard deviations, and highest and lowest individual plasma patterns of the 3 EE preparations were indistinguishable. The administration of 50 mcg of mestranol resulted in an average area under the curve EE of 963 +- 544, whereas the dose 35 mcg of EE produced an area under the curve of 1036 +- 483, thus 35 mcg of EE proved to be a stronger dose than 50 mcg of mestranol. Inter- and intraindividual variability was demonstrated in a study: 24 patients received 35 mcg EE formulations and 27 others received 50 mcg mestranol agents. 3 identical formulations by different manufacturers proved to be bioequivalent. Extreme values ranged from -79% to +134% of the mean of the 3 determinations per individual. Clinical implications of these findings are that plasma EE levels engendered by 35 mcg EE may be indistinguishable from those produced by 50 mcg in another person. 2 to 3 mcg of moxestrol (the 11 beta-methoxy derivative of EE) is an effective contraceptive, as it is 10 times as potent as EE. Exposure of certain cell clones to estradiol, EE, and stilbestrol causes formation in vitro to foci of transformed (neoplastic) cells. However, moxestrol did not produce such cell transformation and these oxidative metabolites increased with estradiol or EE but not with moxestrol. This does not prove the oncogenic role of estrogens in humans, but it offers a new approach in the development of safer estrogens. Language: English Keywords: LITERATURE REVIEW | ETHINYL ESTRADIOL | MESTRANOL | NORETHINDRONE | ESTROGENS | COMPARATIVE STUDIES | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Hormones | Endocrine System | Physiology | Biology | Studies | Research Methodology Document Number: 062156 |
| 15. Title: [Characteristics of estrogens and gestagens] Charakteristik der Estrogene und Gestagene. Author: Goretzlehner G; Kohler G Source: ZEITSCHRIFT FUR ARZTLICHE FORTBILDUNG. 1990;84(1-2):7-12. Abstract: The most important synthetic orally effective estrogens are ethinyl estradiol (EE) and mestranol as well as the depot testrogens, quinestrol, and turisteron. 1.1.5 mg of EE and 1.5-2.0 mg of mestranol are the minimal proliferation doses of a quiescent endometrium within 14 days, while the ovulation inhibition dose of EE is .7 mg between the 5th and 15th days of menstruation. In 1-phase preparations, 20 mcg of EE is used, and in sequential pills, 50 mcg of EE is used. Low doses have diminished the stability of the menstrual cycle, increased spotting, and rushed ovulation. Micropills contain <50 mcg of EE, medium-dose pills contain 50 mcg of EE, and high-dose pills contain >50 mcg of EE. THe average dose of mestranol is 80 mcg. The first 2-phase preparations (sequential pills) were followed by normo-phasic pills: gestagen taken from the 8th day in addition to estrogen. Estrogen-gestagen combination and normo-phasic pills protect against endometrial carcinoma. Weekly pills (Deposition) are taken once a week: 1 pill containing 1 mg of EE for 3 weeks followed by 10 mg of norethisterone acetate on the 4th weeks. Usually, hormonal withdrawal bleeding ensues 2-3 days after gestagen application. The Pearl Index value is 1-2. EE sulfonate therapy is recommended for no longer than 2 years because of the risk of hyperplasia of the endometrium. 4-5 mg of quinestrol (3-cyclopentylether of EE) is used as a once-a-month pill with chlormadinone acetate, norethisterone acetate (NEA), quingestanol, or levonorgestrel (LNG) taken on the 25th day of the cycle. Synthetic gestagens consist of progesterone derivatives (retroprogesterones, 17-hydroxyprogesterone) and of testosterone derivatives (19-nortestosterone, 3-desoxy-19-nortestosterone). They cause the secretional transformation of a proliferated endometrium. The bioavailability of micronized pills is greater: the transformation dose of LNG is 5-6 mg, and of micronized LNG it is 2.5 mg. Chlormadinoacetate (CMA), a 17-alpha-hydroxyprogesterone derivative, is injected sc in fatty tissue. CMA is antiandrogenic, and after 3 days only 17% is excreted in the urine and stool. 50-60% of NEA is bioavailable when taken orally, 50-70% of it is excreted in the urine after 4 days, and 30-40% is eliminated in the stool. LNG is a very strong gestagen and antiestrogen reaching the highest concentration 1-2 hours after ingestion. By replacing sex hormone binding globulin bound testosterone, it is slightly androgenic. The maximum serum level of dienogest (DNG) is reached 1-2 hours after administration. DNG is anti-androgenic; it does not cumulate, but wide fluctuations of plasma levels cause bleeding. Language: German Keywords: GERMANY | CRITIQUE | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | ORAL CONTRACEPTIVES, LOW-DOSE | HORMONES | CONTRACEPTIVE AGENTS, ESTROGEN | ETHINYL ESTRADIOL | MESTRANOL | CONTRACEPTIVE MODE OF ACTION | CHLORMADINONE ACETATE | QUINGESTANOL ACETATE | CONTRACEPTIVE AGENTS, PROGESTIN | Europe, Central | Europe | Developed Countries | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Endocrine System | Physiology | Biology | Contraceptive Agents, Female | Contraceptive Agents Document Number: 062901 |
| 16. Title: Gastrointestinal disease and oral contraception. Author: Hanker JP Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1990 Dec;163(6 Pt 2):2204-7. Abstract: THe recent trend toward decreased dosages of estrogen and progestogen in oral contraceptives (OCs) makes it especially important that attention be directed toward additional factors-- dietary factors, gastrointestinal disturbances or diseases, or drugs that interact with OCs--that may further reduce the bioavailability of steroids and thus compromise contraceptive protection. At present, there is no evidence that antibiotics interfere with OC steroids at the level of enterohepatic circulation; also unlikely is a clinically significant interaction between OCs and antacids. Unlike estrogens, progestogens do not undergo enterohepatic recirculation as unchanged drugs; presumably due to the lack of direct conjugation at the 17 position. Thus, no impact on contraceptive efficacy is produced by disruptions in progestogen metabolism. On the other hand, there is an ample body of research suggesting a link between OCs and chronic inflammatory bowel disease, especially Crohn's disease. The finding of reduced bioavailability of estrogen and progestogen in women who have undergone jejunoileostomy demonstrates that OCs are mainly absorbed in the small bowel and that contraceptive efficacy is related to its absorptive capacity. Overall, it is recommended that careful attention be given to OC acceptors with chronic inflammatory disease, non-colonic diarrhea, ileostomy, and jejunoileal bypass. Language: English Keywords: ORAL CONTRACEPTIVES | ESTROGENS | PROGESTERONE | DRUG INTERACTIONS | HEPATIC EFFECTS | GASTROINTESTINAL EFFECTS | STEROID METABOLIC EFFECTS | CONTRACEPTION FAILURE | ETHINYL ESTRADIOL | MESTRANOL | ANTIBIOTICS | Contraceptive Methods | Contraception | Family Planning | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Drugs | Treatment | Metabolic Effects | Contraceptive Usage | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents Document Number: 064787 |
| 17. Title: Summary and update of the Oxford-based studies. Author: McPherson K Source: In: Oral contraceptives and breast cancer. The implications of the present findings for informed consent and informed choice, edited by R.D. Mann. Carnforth, England, Parthenon Publishing Group, 1990. :55-66. Abstract: A summary of 5 matched control studies on oral contraceptives and breast cancer conducted by the Department of Community Medicine, Oxford, and drawing subjects from 8 London teaching hospitals, Oxford and Edinburgh is analyzed. For discussion purposes, 4 studies of 1176 matched case- control pairs aged <50 were massed as "Study A," and 1125 pairs aged <64 are called "Study B." All results showed no increased risk of use of orals for developing breast cancer, except a group of women <45 in Study B. The women who had used pills for 1-4 years before 1st term pregnancy incurred a risk of 1.97, while those using for 4 or more years had a risk of 2.59. The linear trend was significant (p<0.01). The data were examined for possible bias due to chance and survey methods, without any indication of differences. The results are discussed as a possible case of a latent effect, possibly due to a long-term process just beginning to emerge, or a multi-stage process. The analogy was made with carcinogenesis caused by diethylstilbestrol which was not evident in early studies, but appeared 22 years later. Only pills containing ethinyl estradiol were among cancer cases in this group. While the data suggest a latent effect of pill use for 4 or more years before 1st pregnancy, only 2 cases and 1 control were in this category, so more studies are needed. Language: English Keywords: UNITED KINGDOM | ETHINYL ESTRADIOL | MESTRANOL | BREAST CANCER | RISK FACTORS | TIME FACTORS | NULLIPARITY | RETROSPECTIVE STUDIES | COMPARATIVE STUDIES | MATCHED GROUPS | LINEAR REGRESSION | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE METHODS | SIDE EFFECTS | United Kingdom | Europe, Western | Europe | Developed Countries | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Biology | Population Dynamics | Demographic Factors | Population | Parity | Fertility Measurements | Fertility | Studies | Research Methodology | Control Groups | Statistical Regression | Data Analysis | Contraceptive Safety | Safety | Public Health | Health | Treatment Document Number: 064337 |
| 18. Title: Oral contraception and breast cancer in New Zealand. Author: Paul C; Skegg DC; Spears GF Source: In: Oral contraceptives and breast cancer. The implications of the present findings for informed consent and informed choice, edited by R.D. Mann. Carnforth, England, Parthenon Publishing Group, 1990. :85-97. Abstract: The risk of breast cancer in oral contraceptive users was examined in a populations-based study in New Zealand, focusing on women aged 25-54 with histologically confirmed breast cancer diagnosed between 1983-1987. 891 cases were selected, with 1864 matched controls taken from election rolls. New Zealand is notable for high prevalence, 20%, of women using oral contraceptives in 1966, long-term use, and early use by young women, predating the trend both in the U.K. and the U.S. study subjects were interviewed by telephone, and results checked from records of general practitioners. The results reported here are based on analysis of 433 cases and 897 controls 2 years into the study. There was no overall association between oral contraception and breast cancer risk, nor was there any increased risk by duration of use, age at 1st use or time since 1st use. The relative of women diagnosed at age 25-34 was 2.2. The lack of effect of pill use before 1st pregnancy was not due to small numbers in this study, since early use is more extensive in New Zealand than in Britain. In this study the risk with pills containing ethinyl estradiol was below 1. These results so far are reassuring, providing strong evidence that there is no increased risk of taking oral contraceptives before age 25 or before the 1st pregnancy. Language: English Keywords: NEW ZEALAND | MESTRANOL | ETHINYL ESTRADIOL | BREAST CANCER | RISK FACTORS | TIME FACTORS | NULLIPARITY | COMPARATIVE STUDIES | MATCHED GROUPS | LINEAR REGRESSION | LONGTERM EFFECTS | RETROSPECTIVE STUDIES | ORAL CONTRACEPTIVES | Developed Countries | Oceania | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Biology | Population Dynamics | Demographic Factors | Population | Parity | Fertility Measurements | Fertility | Studies | Research Methodology | Control Groups | Statistical Regression | Data Analysis | Contraceptive Methods Document Number: 064335 |
| 19. Title: [Pharmacodynamics of synthetic estrogens. Review article] Farmacodinamica de los estrogenos sinteticos. Articulo de revision. Author: Sojo-Aranda I; Cortes-Gallegos V Source: Ginecología y Obstetricia de México. 1990 Oct;58:277-83. Abstract: Some studies of the peripheral concentration and concentration in reproductive tissues of ethinyl estradiol (EE) and mestranol are reviewed. Orally administered EE is observable in the peripheral circulation within 30-60 minutes. A 1970 study of radioactive EE demonstrated that the endometrium and ovaries captured most of the EE, with levels in the uterus and serum much lower. Adipose tissue was found to be important in storing the hormones. Other studies of radioactive mestranol and EE demonstrated that the compounds were deposited in other organs in significant quantities and that the deposits were perhaps irreversible or of very slow release. The ability of estrogens to remain concentrated at the systemic level and not just in reproductive organs may be related to some adverse effects reported in women using oral contraceptives (OCs). Advances in radiochemistry and immunology in the 1960s made it possible to measure steroid hormone levels in different tissues. The capacity of the endometrium to concentrate natural steroids such as 17-beta estradiol and progesterone during the ovulatory menstrual cycle was demonstrated in 1978. A subsequent study showed that the endometrium captured and stored the synthetic estrogen EE in even greater concentrations than the natural estrogen estradiol. A study of the pharmacodynamics of EE in hysterectomized women showed that 24 hours after the 1st dose of 30 mcg the EE was not detected in the peripheral circulation. But the peripheral concentration increased with continuous daily administration of 30 mcg of EE. 27 days after suppression of treatment it was still detectable in the peripheral circulation. Another experiment was designed to measure simultaneously the concentrations of EE in the peripheral circulation and in the endometrial tissue of 36 women terminating use of OCs containing norgestrel and EE after 2-36 months of treatment. The study showed that synthetic estrogen was still observable in the endometrial tissue 1 month after discontinuing OC use. Inexplicably, levels of EE were higher in the circulation in the cycle after treatment than in the final treatment cycle. 5 of the women participated in the study for 3 posttreatment cycles. EE was observed in the circulation 1 month after termination of OC use in 5 women, 2 months after termination in 4 women, and 3 months after termination in 3 women. The persistence of EE in the tissue months after termination of treatment suggests the need for further research and assessment of possible resulting risks. Language: Spanish Keywords: MEXICO | LITERATURE REVIEW | ETHINYL ESTRADIOL | MESTRANOL | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE METHODS | SIDE EFFECTS | North America | Latin America | Americas | Developing Countries | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Safety | Safety | Public Health | Health | Treatment Document Number: 067425 |
| 20. Title: A comparative study of Norinyl 1/35 versus Lo-Ovral in Ile-Ife Nigeria. Author: Ayangade O; Akinyemi A Source: INTERNATIONAL JOURNAL OF GYNAECOLOGY AND OBSTETRICS. 1989 Oct;30(2):165-70. Abstract: A comparative study of 2 combined oral contraceptives was conducted on 100 women in Ile-Ife, Nigeria. Women were randomly allocated to receive either Lo-Ovral or Norinyl 1/35. Lo-Ovral and Norinyl 1/35 have similar low dose estrogen content, but different progestogen formulations and dosages. The women in the Lo-Ovral group were significantly younger than the Norinyl 1/35 group, with mean ages of 28.3 and 30.6 years respectively. There was no significant statistical difference between the education levels of the 2 groups. The mean parity of the groups was not statistically different, either. Only 3 women had serious complaints at the onset. 15 women, (31.9%) in Norinyl 1/35 and 9 (18.8%) in the Lo-Ovral group reported at least 1 menstrual complaint. However, the difference between the groups was not significant. 28 women (59.6%) in the Norinyl group, and 23 women (47%) in the Lo-Ovral group reported at least 1 complaint. All the women who had initial serious complaints chose to continue the method, and did not report the problems again at follow-up visits. Most of the other complaints decreased in most users with use. 10 women (21.2%) in the Norinyl group and 12 women (25.0%) in the Lo-Ovral group discontinued the method during the study. The difference was not statistically significant. Travel/movement was the primary reason for not continuing in both groups. The loss to follow-up rate was 33.3% and 27.1% for Norinyl and Lo-Ovral, respectively. No pregnancies were reported during the study. The dosages of estrogen used appear very effective and the progesterone component well tolerated. Gastrointestinal symptoms were minimal. Side effects did not contribute to the high rate of discontinuation. Language: English Keywords: COMPARATIVE STUDIES | CONTRACEPTIVE AGENTS, FEMALE | NORETHYNODREL | MESTRANOL | NIGERIA | ORAL CONTRACEPTIVES, LOW-DOSE | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, PROGESTIN | ETHINYL ESTRADIOL | CONTRACEPTION CONTINUATION | AGE FACTORS | CLINICAL RESEARCH | FAMILY PLANNING ACCEPTOR CHARACTERISTICS | RESEARCH REPORT | SIDE EFFECTS | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | Studies | Research Methodology | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Africa, Western | Africa, Sub Saharan | Africa | Developing Countries | Oral Contraceptives | Contraceptive Methods | Contraceptive Usage | Population Characteristics | Demographic Factors | Population | Family Planning Acceptors | Family Planning Programs | Treatment | Contraceptive Safety | Safety | Public Health | Health Document Number: 059058 |
| 21. Title: Exacerbation of adenomyosis symptomatology by estrogen-progestin therapy: a case report and histopathological observations. Author: Falk RJ; Mullin BR Source: INTERNATIONAL JOURNAL OF FERTILITY. 1989 Nov-Dec;34(6):386-9. Abstract: A 32 year old woman underwent exploratory surgery because she had severe dysmenorrhea, the physicians found fibroids, and they excised pelvic endometriosis. 1 year later, she sought the assistance of the Center for Fertility and Reproductive Endocrinology at the Columbia Hospital for Women in Washington, D.C. because of continual dysmenorrhea and pain. A physician at the center treated her with Ovulen, a continuous estrogen/progestin therapy, yet her pain worsened. Upon a pelvic reexamination 16 months later, a physician noted a tender, enlarged, and irregularly shaped uterus (16 cm from fundus to cervix and 726g). Further, pelvic sonography detected multiple leiomyomas, 1 being 9x7 cm. The physician did a laparotomy to perform a myomectomy and therefore preserve fertility, but could not establish cleavage planes. Thus she needed to undergo a hysterectomy. Pseudodecidualized adenomyotic islands were found in the enlarged posterior myometrial wall. The results of this woman's use of Ovulen are similar to previous research on prostaglandins' role in which they act as intermediaries in decidual metaplasia. This case report affirms that progestins do not treat adenomyosis and cause significant exacerbation of its symptoms. Based on previous research and this case, the author believes that an undefined luminal component and progestin stimulation causes development of a decidual response in the uterus. Once the stimulus is defined, be it chemical, infectious, or mechanical, researchers could identify other approaches for the symptomatic relief of this debilitating and difficult to diagnose ailment. Language: English Keywords: DISTRICT OF COLUMBIA | CONTRACEPTIVE AGENTS, FEMALE | ETHYNODIOL DIACETATE | MESTRANOL | DECIDUAL CELL REACTION | MYOMETRIAL EFFECTS | SIGNS AND SYMPTOMS | PAIN | LAPAROTOMY | HYSTERECTOMY | CASE STUDIES | UNITED STATES OF AMERICA | Developed Countries | North America | Americas | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Estrogen | Cytologic Effects | Physiology | Biology | Myometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Diseases | Surgery | Treatment | Gynecologic Surgery | Urogenital Surgery | Studies | Research Methodology Document Number: 060280 |
| 22. Title: Oral contraceptive treatment for rheumatoid arthritis: an open study in 10 female patients. Author: Hazes JM; Dijkmans BA; Vandenbroucke JP; Cats A Source: BRITISH JOURNAL OF RHEUMATOLOGY. 1989;28 Suppl 1:28-30. Abstract: 10 female patients (median age 37 years, range 23-45) with active rheumatoid arthritis (RA; 9 seropositive, 1 seronegative, 7 erosive, 3 nonerosive) were treated during 6 months with 1 of the earlier (higher- dosed) oral contraceptives (Lyndiol, each tablet containing 2.5 mg lynestrenol and 0.00w5 mg ethinyl estradiol). None of the patients had been previously treated with a disease-modifying drug. In 1 patient, therapy with Lyndiol was stopped within 14 days after initiation because of vomiting. 3 of the 9 remaining patients stopped therapy after 3 months because of inefficacy. Erythrocyte sedimentation rate deteriorated during the study. Except for the number of swollen joint, no clinical or laboratory parameters improved. The authors conclude the Lyndiol has no disease-modifying effect in RA. (author's) Language: English Keywords: NETHERLANDS | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, FEMALE | LYNESTRENOL | MESTRANOL | DISEASES | ANALGESIA | TREATMENT | EVALUATION | ADMINISTRATION AND DOSAGE | Europe, Western | Europe | Developed Countries | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents | Contraceptive Agents, Progestin | Contraceptive Agents, Estrogen | Drugs Document Number: 060738 |
| 23. Title: Bioequivalence of Norethin and Ortho-Novum in healthy females. Author: Kisicki J Source: ADVANCES IN THERAPY. 1989 Nov-Dec;6(6):261-8. Abstract: The pharmacokinetic profiles and in particular the bioavailability of Norethin 1/35E (norethindrone 1 mg, ethinyl estradiol [EE] 35 mcg), and Norethin 1/50M (norethindrone 1 mg, mestranol 50 mcg) were compared with those of Ortho-Novum 1/35 and Ortho-Novum 1/50, respectively, in 2 separate studies. Both studies employed a full crossover design and a 7-day washout period between treatments. Blood samples were obtained from 20 minutes to 36 hours after oral drug administration for determination of plasma concentrations of norethindrone and EE by radioimmunoassay. Analysis of the plasma concentration vs time curves for both norethindrone and EE after Norethin 1/35E and Ortho-Novum 1/35 administration demonstrated no significant differences between the 2 formulations in maximum plasma concentration (Cmax), area under the curve from the time of drug administration until the last plasma sample (AUCO-36), or AUC from the time of drug administration extrapolated to infinity (AUCO-infinity). Similarly, in the comparison of Norethin 1/50M and Ortho-Novum 1/50, there were no significant differences in Cmax, AUCO-36, and AUCO-infinity between the 2 formulations. Thus, there is complete bioequivalence between Norethin 1/35E and Ortho-Novum 1/35, and between Norethin 1/50M and Ortho-Novum 1/50. (author's) Language: English Keywords: MESTRANOL | NORETHINDRONE | ETHINYL ESTRADIOL | LABORATORY EXAMINATIONS AND DIAGNOSES | ORAL CONTRACEPTIVES | HEMATOLOGIC TESTS | ANALYSIS | ADMINISTRATION AND DOSAGE | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Examinations and Diagnoses | Contraceptive Methods | Laboratory Procedures | Research Methodology | Drugs | Treatment Document Number: 065000 |
| 24. Title: Oral contraceptives: significance of their effects in man and relationship to findings in animal models. Author: Pasquale SA Source: TOXICOLOGIC PATHOLOGY. 1989;17(2):396-400. Abstract: A historical review of the 28-year history of oral contraceptives from the viewpoint of correlation or lack thereof between drug toxic and pathologic effects seen in laboratory animals and those seen clinically is presented. Early high dose pills were expected to cause growth of uterine fibroids, but instead they had the unexpected effect of an estrogen dose-related venous thrombosis risk. Work on rats predicted that pills would cause liver cancers, but instead to slightly increase the incidence of being liver adenomas in women. Similarly, rat research predicted pituitary microadenomas. Pituitary effects in women, while rare, are thought to be due to prescription of pills to women with irregular cycles of pituitary origin. Progestins of the 17-acetoxy series were considered likely to produce breast cancers, as they had in beagle dogs. They apparently have not done so in women. They were reports in the mid-1970s that sequential pills containing 100 mcg ethinyl estradiol cause endometrial carcinoma. These pills have been discontinued. Recent evidence has been accumulating that low-dose pills containing levonorgestrel increase blood pressure and possible LDL-cholesterol. Risk of death from vascular disease, however, seems to be concentrated in women who smoke, especially those over 35. Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | HISTORICAL REVIEW | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | CHLORMADINONE ACETATE | MESTRANOL | LEVONORGESTREL | CONTRACEPTIVE AGENTS, FEMALE | NORETHYNODREL | NORETHINDRONE | CARDIOVASCULAR EFFECTS | HYPERTENSION | THROMBOEMBOLISM | LIVER NEOPLASMS | LIPID METABOLIC EFFECTS | BREAST CANCER | FIBROIDS | PITUITARY GLAND | LABORATORY ANIMALS | COMPARATIVE STUDIES | Developed Countries | North America | Americas | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents | Contraceptive Agents, Estrogen | Physiology | Biology | Vascular Diseases | Diseases | Embolism | Neoplasms | Lipids | Cancer | Neoplasms, Benign | Endocrine System | Clinical Research | Research Methodology | Studies Document Number: 060515 |
| 25. Title: Manufacturers phase out high-dose oral contraceptives. Source: FDA DRUG BULLETIN. 1988 Aug;18(2):19. Abstract: The 3 manufacturers of high-dose oral contraceptives (OCs) have notified prescribers that they are discontinuing the production and distribution of these products. These "Dear Doctor" letters follow recommendations of FDA's Fertility and Maternal Health Drug Advisory Committee that OCs containing more than 50 mcg of estrogen no longer be marketed because these formulations are no more effective than the lower-dose formulations. In a presentation before the advisory committee, a spokesman for the American College of Obstetricians and Gynecologists opposed continued use of the high-dose formulations. The formulations being phased out contain 75-100 mcg of estrogen. The manufacturers and products are: Ortho Pharmaceutical--Ortho-Novum 1/80 and Ortho-Novum 2 mg; Syntex--Norinyl 2 and Norinyl 2+80; G.D. Searle--Enovid E-21 and Ovulen. The manufacturers notified physicians at the end of March that these products would be discontinued in 6 months, and advised clinicians to transfer patients using the high-dose products to lower-dose formulations containing 30-50 mcg of estrogen. FDA has estimated that 3% of patients taking OCs--or about 400,000 women--were taking the high-dose products before the manufacturers announced their withdrawal. FDA has recommended, since January 1970, that physicians prescribe the lowest possible effective dose OC (see April 1970 Drug Bulletin). (full text) Language: English Keywords: ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | PRODUCTION | ECONOMIC DEVELOPMENT | NORETHINDRONE | MESTRANOL | HORMONES | REPRODUCTIVE CONTROL AGENTS | NORETHYNODREL | CHANGES | Contraceptive Methods | Family Planning | Contraceptive Agents | Macroeconomic Factors | Economic Factors | Contraceptive Agents, Progestin | Contraceptive Agents, Estrogen | Endocrine System | Physiology | Biology | Social Change Document Number: 056412 |
| 26. Title: Oral contraceptives and breast cancer: what has 20 years of research shown? Author: Buehring GC Source: BIOMEDICINE AND PHARMACOTHERAPY. 1988;42(8):525-30. Abstract: Animal model, histologic, and epidemiologic studies over a 20 year period do not support an increased risk of breast cancer with oral contraceptive (OC) use. Even though the US Food and Drug Administration required using the dog, the monkey, and the rodent as animal models for OC testing at the end of the 1970s, research showed that theses models do not adequately match humans. For example, primates rarely get breast cancer yet the incidence for humans ranges from 7%-10%. The beagle experiences 1-2 estrus cycles/year while humans have 12 menstrual cycles/year. Although rodents have a breast cancer incidence similar to humans, study results varied widely depending on strains, doses, and/or administration routes. As of 1988, no case control or cohort studies had demonstrated a statistically significant overall increase in breast cancer incidence in OC users vs. never users. Yet at least 18 studies in which the investigator corrected for major confounding variables showed an insignificant increased risk of breast cancer among certain subsets of women associated with OC use. Various studies supported the theory that OCs may augment multiplication of already altered cells. For example, OCs induced an increased incidence of mammary cancer only in animal models and strains which had an incidence of mammary cancer at least as high as humans. Further, mammographic studies of breast dysplasia revealed that OC users have >18 times the risk of developing breast cancer than do nonusers. Additionally, in breast tissue culture studies, combination OCs containing norethynodrel-mestranol and norgestrel-ethinyl estradiol triggered cancerous cells to multiply faster than normal cells. Research must continue so as to know how to alter OCs to reduce any tumor promotion capabilities without foregoing contraceptive efficiency. Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | CONTRACEPTIVE AGENTS, PROGESTIN | ETHINYL ESTRADIOL | NORETHYNODREL | NORGESTREL | PROGESTERONE | BREAST CANCER | HISTOLOGY | LABORATORY ANIMALS | IN VITRO | EPIDEMIOLOGIC METHODS | ORAL CONTRACEPTIVES | MESTRANOL | Developed Countries | North America | Americas | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Cancer | Neoplasms | Diseases | Clinical Research | Research Methodology | Contraceptive Methods Document Number: 058709 |
| 27. Title: Oral contraceptives. Author: Chaudhuri SK Source: In: Practice of fertility control: a comprehensive textbook. 2nd ed., [by] S.K. Chaudhuri. New Delhi, India, B.I. Publications, 1988. :102-24. Abstract: Despite the fact that steroidal oral contraceptives are at present the most effective means of family planning, used by 60 million women worldwide, they are used by only 2.3% of all contraceptive users in India. Their avoidance is due to unfounded fears of side effects. Modern oral contraceptives are of 4 types: combined low-dose pills, phasic pills, mini-pills, and postcoital hormonal pills. The combined low-dose pills are of 2 kinds: 1) estrogens (ethinyl estradiol or mestranol) and 2) progestagens (norethisterone or norgestrel). Combined low-dose hormonal pills are taken orally in the 5th day for 3 weeks, followed by 1 week off. Phasic pills are of 2 types: triphasic and biphasic. The phasic pill of choice is the triphasic Triquilar -- .05 mg levonorgestrel and .03 mg ethinyl estradiol per day for 6 days, .075 mg levonorgestrel and .04 mg ethinyl estradiol per day for 5 days, and .125 mg levonorgestrel and .03 mg ethinyl estradiol per day for 10 days. Mini-pills, containing progestagens only, are taken daily by subjects in whom estrogen is contraindicated. Estrogen and norgestrel may be used as postcoital contraceptives in emergency situations. The combined estrogen/progestagen pills work by inhibiting ovulation, by altering the endometrium and thus preventing ovum implantation, and by altering the cervical mucus to inhibit sperm penetration. The phasic pills and the postcoital pills work by altering the endometrium to prevent ovum and blastocyst implantation respectively. If used correctly, oral contraceptives have a failure rate of .07 per 100 woman-years. In developed countries, where oral contraceptives account for 29% of contraceptive use, continuation rates are high 50% to 70% after 2 years). But in developing countries, where oral contraceptives comprise only 12% of contraceptive use, continuation rates are low (4% to 10% at 18 months in India). Oral contraceptives, not only are the most effective method for preventing pregnancy, they have a curative effect on menstrual disorders and a stabilizing effect on the menstrual cycle. They have also been shown to reduce the risk of pelvic inflammatory disease, hirsutism and acne, endometriosis, anemia, ectopic pregnancy, benign breast diseases, ovarian cysts, uterine fibromyoma, endometrial and ovarian cancer, rheumatoid arthritis, and thyroid disorders. The greatest danger from use of combined oral contraceptives is the increased risk of myocardial infarction, cerebrovascular accident, and pulmonary embolism, especially in women over 45 and smokers. The modern lower dosage of estrogens should ameliorate these risks. Some evidence exists linking oral contraceptives to an increased risk of cervical, breast, and liver cancer. Persistent amenorrhea after contraceptive termination may indicate pituitary microadenoma. Diabetic women and women taking barbiturates, sulfonamides, rifampicin or anticonvulsant drugs may require adjusted dosages of the contraceptive agents. Obese women who smoke should not take them. Minor side effects reported include nausea and vomiting, sore breasts, vaginal discharge, oligomenorrhea, weight gain, headache, chloasma, and acne. In general, the benefits of oral contraceptives far outweigh the risks. Research continues in the development of pills with fewer side effects, long-acting (such as once-a-month) pills, and postcoital pills. Language: English Keywords: INDIA | DEVELOPING COUNTRIES | DEVELOPED COUNTRIES | CONTRACEPTION | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTIVE AGENTS, PROGESTIN | PROGESTERONE | NORGESTREL | MESTRANOL | CONTRACEPTIVE AGENTS, POSTCOITAL | FERTILITY CONTROL, POSTCOITAL | HORMONES | OVULATION SUPPRESSION | ENDOMETRIUM | CERVICAL MUCUS | MYOCARDIAL INFARCTION | CARDIOVASCULAR EFFECTS | CONJUGATED ESTROGENIC SUBSTANCES | ESTROGENS | ETHINYL ESTRADIOL | LEVONORGESTREL | EMERGENCY CONTRACEPTION | OBESITY | TOBACCO USE | DIABETES | NORETHINDRONE ACETATE | ETHYNODIOL DIACETATE | Asia, Southern | Asia | Family Planning | Contraceptive Methods | Contraceptive Agents | Progestational Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Estrogen | Contraceptive Mode of Action | Uterus | Genitalia, Female | Genitalia | Urogenital System | Cervix | Heart Diseases | Diseases | Body Weight | Behavior | Norethindrone Document Number: 047668 |
| 28. Title: Endometrial response to the use of a sequential oral contraceptive. Author: Coppens M; Thiery M Source: JOURNAL OF OBSTETRICS AND GYNAECOLOGY. 1988;8(3):281-4. Abstract: Belgium is 1 of the few countries where sequential oral contraceptives are still commercially available. The authors investigated the endometrial effect of Ortho-Novum SQ (14 tablets of 100 mcg mestranol and 7 tablets of 100 mcg mestranol + 2 mg norethisterone) in 222 biopsy specimens obtained from 184 asymptomatic Caucasian women (mean +or- s.d, age and parity, 34.6 +or- 6.7 and 2.0 +or- 1.0, respectively) who had used this sequential OC during an average of 52.5 months. Notwithstanding predominantly longterm use of Ortho-Novum SQ, 43% of the tissue samples had normal proliferative or luteal endometrium. The data suggest a positive correlation between the endometrial response and the duration of pill use. No premalignant or malignant changes were found. In 15 of 24 subjects for whom multiple biopsy specimens were available, the histological picture was static; 7 showed regression and only in 2 were the changes progressive, although never more severe than minor 'class 2' lesions. These results, which are at variance with those reported for users of other sequential brands (mainly Oracon), suggest that prolonged use of Ortho-Novum SQ does not enhance the risk of endometrial cancer in premenopausal women having no additional risk factors for the development of this type of neoplasia. (author's) Language: English Keywords: BELGIUM | EUROPE, WESTERN | EUROPE | ORAL CONTRACEPTIVES, PHASIC | ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | ENDOMETRIAL EFFECTS | UTERINE EFFECTS | GENITAL EFFECTS, FEMALE | UROGENITAL EFFECTS | NORETHINDRONE | MESTRANOL | HORMONES | REPRODUCTIVE CONTROL AGENTS | HISTOLOGY | ANATOMY | RISK FACTORS | ENDOMETRIAL CANCER | CANCER | NEOPLASMS | DISEASES | CHANGES | Developed Countries | Oral Contraceptives, Combined | Contraceptive Methods | Family Planning | Contraceptive Agents | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Estrogen | Endocrine System | Social Change Document Number: 056237 |
| 29. Title: Vaginal pills: systemic contraception induced by vaginal administration of contraceptive pills. Author: Coutinho EM Source: In: Contraception research for today and the nineties: progress in birth control vaccines, [edited by] G.P. Talwar. New York, New York, Springer-Verlag, 1988. :67-79. (Progress in Vaccinology Volume 1.) Abstract: Clinical trials with the various pills reveal a significantly lower occurrence of vaginal problems requiring discontinuation in vaginal pill users than those reported by vaginal ring users. Ring expulsion, interference with coitus, the user's dislike or difficulty with insertion or removal of the ring, unpleasant ring odor, difficulty with storage or ring loss, which account for the majority of vaginal ring users' discontinuation, are absent among vaginal pill users. Few vaginal pill users discontinue because of vaginal problems. Vaginal discharge itself did not appear to be a serious problem. Its incidence in vaginal pill users (20%) is not higher than that occurring in oral contraceptive or IUD users, suggesting that its occurrence may be unrelated to vaginal pill use. Pathogenic agents identified in the vaginal discharge of women using the vaginal pill were the same agents frequently found in vaginal discharge of women using other contraceptive methods. Furthermore, patients may be successfully treated for vaginitis without necessarily interrupting vaginal pill insertion, even in cases where vaginal creams are used. This is possible because the vaginal pill remains a relatively short time in the vagina, dissolving quickly and being completely absorbed within 1 or 2 hours. Despite the low plasma levels, cycle control is as good or better than that reported for low-level combined oral contraceptives. The incidence of intermenstrual bleeding and spotting is minimal. The continuation rate of the vaginal pill at 1 year (64%) also compares favorably with continuation rates recorded in most family planning clinics for ring users (48%) and oral contraceptive users (47%). Vaginal pills should be indicated for women both at the beginning (adolescents) and at the end of their reproductive life span because they are better tolerated and provoke almost no side effects. Vaginal pills should also be tried by women for whom IUDs are contraindicated or those who develop gastrointestinal side effects while on oral contraceptives. Studies in progress show that the incidence of nausea is significantly reduced when high-dose estrogens or progestogens are administered by the vaginal route as postcoital contraceptives. Language: English Keywords: CONTRACEPTIVE AGENTS, SIDE EFFECTS | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | FAMILY PLANNING | VAGINA | GENITALIA, FEMALE | GENITALIA | WOMEN | VAGINAL RING | NORGESTREL | HORMONES | ETHINYL ESTRADIOL | LEVONORGESTREL | NORETHINDRONE | MESTRANOL | Contraceptive Agents | Urogenital System | Physiology | Biology | Demographic Factors | Population | Contraceptive Methods | Contraceptive Agents, Progestin | Endocrine System | Contraceptive Agents, Estrogen Document Number: 052852 |
| 30. Peer Reviewed Title: Assessment of a new low-dose once-a-month injectable contraceptive. Author: Garza-Flores J; Jimenez-Thomas S; Salomon-Andonie J; Diaz-Sanchez V Source: CONTRACEPTION. 1988 May;37(5):471-81. Abstract: Norethisterone (NET) in combination with mestranol (ME), in a macrocrystalline aqueous suspension that provides sustained release of steroids, was assessed as a once-a-month injectable contraceptive in 10 healthy women of reproductive age. The ovarian function was studied before and after the intramuscular administration of 12 mg NET + 1.2 mg ME, delivered as crystals of 150 mcm average size. Serial blood samples were taken throughout the injection intervals in all women to measure sperm progesterone, estradiol, and NET. The NET/ME preparation effectively inhibited ovulation in 23 of 25 injection intervals studied. The administration of this formulation induced in some women a small degree of follicular maturation not followed by luteal activity. The endometrial bleeding patterns after each injection showed a bleeding-free period of 2-3 weeks. The overall data demonstrate that the parenteral administration of a macrocrystalline steroid preparation of NET/ME can bring about a sustained release contraceptive system at a substantially lower dose than those currently employed in a once-a-month injectable contraceptive. (author's) Language: English Keywords: INJECTABLES | EVALUATION | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | NORETHINDRONE | MESTRANOL | HORMONES | REPRODUCTIVE CONTROL AGENTS | OVULATION SUPPRESSION | OVULATION | REPRODUCTION | LABORATORY EXAMINATIONS AND DIAGNOSES | EXAMINATIONS AND DIAGNOSES | BLEEDING | SIGNS AND SYMPTOMS | ESTRADIOL | ESTROGENS | PROGESTERONE ANALYSIS | CORPUS LUTEUM HORMONES | ANALYSIS | Contraceptive Methods | Family Planning | |