| 1. Title: A changing pattern in the association of oral contraceptives and the different groups of congenital limb deficiencies. Author: Czeizel AE; Kodaj I Source: CONTRACEPTION. 1995 Jan;51(1):19-24. Abstract: In Hungary, researchers analyzed 1975-1984 population-based and revised data on 537 children with isolated congenital limb deficiency (CLD) (i.e., cases with at least 1 affected limb) and data on 537 age-matched controls with no CLD. They wanted to determine the association between periconceptional use of oral contraceptives (OCs) and CLD. Personal examination and/or medical documents confirmed reported diagnoses. They separated the isolated CLD cases into terminal transverse CLD, amniogenic CLD, radial and tibial CLD, ulnar-fibular CLD, split hand and/or foot CLD, and intercalary CLD. Periconceptional use of Bisecurin (relatively high dose of 1 mg ethynodiol diacetate and 0.05 mg ethinyl estradiol) was significantly associated with terminal transverse CLD (adjusted odds ratio [AOR] = 1.9; p = 0.03). It was also significantly associated with monomelic CLD (AOR = 1.6; 9.6% vs. 2.9%; p = 0.0015). The monomelic cases comprised 19 terminal transverse cases, 6 amniogenic cases, 7 radial cases, 3 atypical split hand cases, and 2 ulnar cases. 19 of the 20 terminal transverse cases were monomelic. Periconceptional use of Continuin (0.5 mg ethynodiol diacetate alone) was associated, but not significantly so, with terminal transverse CLD (6 cases vs. 1 control; p = 0.06). These findings suggest that use of OCs with a high dose of ethynodiol diacetate increases the risk of terminal transverse defect. Use of low dose OCs likely minimizes this risk. Language: English Keywords: HUNGARY | CASE CONTROL STUDIES | RETROSPECTIVE STUDIES | ORAL CONTRACEPTIVES, COMBINED | CONGENITAL ABNORMALITIES | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES, LOW-DOSE | ADMINISTRATION AND DOSAGE | Developing Countries | Europe, Central | Europe | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Neonatal Diseases and Abnormalities | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Drugs | Treatment Document Number: 102295 |
| 2. Title: Menometrorrhagia in an oral contraceptive user. Author: Murphy NJ; Wallace DL; Behrend AE Source: JOURNAL OF FAMILY PRACTICE. 1993 Feb;36(2):229-31. Abstract: Endometrial carcinoma is the most frequent malignancy of the female reproductive tract, and irregular vaginal bleeding is its most common symptom. It is most common among postmenopausal women and is associated with obesity, nulliparity, and anovulation. Oral contraceptive (OC) use and tobacco smoking have been reported to protect against it. A 30-year-old nulligravida nulliparous woman presented with menometrorrhagia. She had had normal menses since age 11, she had smoked a pack of cigarettes a day for 15 years, and had been obese since age 15 (weighing 302 pounds). At age 26, she started taking a combination OC containing .1 mg ethynodiol diacetate and 35 mcg ethynyl estradiol (EE). 4 years later she gradually developed menorrhagia which improved upon changing the OC to .3 mg norgestrel and 30 mcg EE. Subsequently she developed early cycle metrorrhagia and was placed on .5 mg norgestrel and 50 mcg EE. She continued having early and midcycle breakthrough bleeding with clots. Physical examination and test results including a PAP smear were normal. She was taken to the emergency department because of continued bleeding. The uterus sounded to 14 cm. Curettings were consistent with grade 1-2, well-differentiated adenocarcinoma of the endometrium. 3 weeks later, she had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal biopsy for cytological examination. The pelvis and the abdomen were free of metastasis. Histological examination revealed a superficially invasive, well-differentiated adenocarcinoma consistent with stage IB, grade 1%. Ploidy analysis uncovered 12.5% tetraploid, with 0% aneuploid or hyperploid cells with 8.5% of the cells in S phase and 21% in the proliferative phase. Both estrogen and progesterone receptors were positive. The ploidy analysis and receptor status were consistent with the low-grade nature of the lesions. Postoperative radiation was not recommended, and the patient was well 6 months postoperatively. Language: English Keywords: UNITED STATES OF AMERICA | MISSOURI | CASE STUDIES | ENDOMETRIAL CANCER | MENORRHAGIA | METRORRHAGIA | OBESITY | TOBACCO USE | NORGESTREL | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | HYSTERECTOMY | Developed Countries | North America | Americas | Studies | Research Methodology | Cancer | Neoplasms | Diseases | Menstruation Disorders | Bleeding | Signs and Symptoms | Body Weight | Physiology | Biology | Behavior | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Gynecologic Surgery | Urogenital Surgery | Surgery | Treatment Document Number: 082936 |
| 3. Title: Effects of desogestrel on carbohydrate metabolism. Author: Shoupe D Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1993 Mar;168(3 Pt 2):1041-7. Abstract: Progesterone and the synthetic progestins used in oral contraceptives are associated with a dose-dependent impairment of carbohydrate metabolism. Hyperinsulinemia and alterations in glucose metabolism are significant risk factors for the development of cardiovascular disease. However, long-term use of OCs does not appear to increase the risk of cardiovascular disease. In addition, long-term studies do not indicate any trend toward diabetes in long-term users. Desogestrel, a new progestin derived from 19-nortestosterone, is highly selective for progesterone receptors, with little affinity for androgen receptors. Of the four small studies using 150 mcg monophasic desogestrel and 30 mcg ethinyl estradiol (EE) mild increases in blood glucose were shown in one study after 6 months and after 12 months in another. In addition, plasma insulin decreased in two studies, increased in one, and remained unchanged in one. In a large cross-sectional study, users of OCs for at least 3 months were compared with nonusers. All OC formulations were associated with a deterioration in glucose tolerance. The smallest effect on both glucose tolerance and insulin secretion, as indicated by the C-peptide response, was found with the desogestrel-containing monophasic preparations. In a follow-up study, the metabolic basis of insulin disturbances was investigated as a consequence of the use of combination OCs containing levonorgestrel, norethindrone, or desogestrel as well as progestin-only formulations (norethindrone or ethynodiol diacetate). The levonorgestrel-containing combinations had the greatest effect on intravenous glucose tolerance tests, insulin, and C-peptide concentrations, followed by desogestrel and low-dose norethindrone. The new low-dose OCs show slight decreases in glucose tolerance, usually from 10% to 15% increases in glucose and from 10% to 30% increases in insulin curves compared with base-line. Desogestrel has been demonstrated to have generally less pronounced effects on these parameters of carbohydrate metabolism. Language: English Keywords: LITERATURE REVIEW | DESOGESTREL | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, LOW-DOSE | CARBOHYDRATE METABOLIC EFFECTS | THROMBOEMBOLISM | CARDIOVASCULAR EFFECTS | LONGTERM EFFECTS | ETHINYL ESTRADIOL | LEVONORGESTREL | NORETHINDRONE | ETHYNODIOL DIACETATE | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Oral Contraceptives | Contraceptive Methods | Metabolic Effects | Physiology | Biology | Embolism | Vascular Diseases | Diseases | Time Factors | Population Dynamics | Demographic Factors | Population | Contraceptive Agents, Estrogen Document Number: 094056 |
| 4. 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 |
| 5. Title: Oral contraceptives and breast cancer. Reply of the authors [letter] Author: Staffa JA; Jones JK Source: FERTILITY AND STERILITY. 1992 Dec;58(6):1272. Abstract: Staff scientists at The Degge Group, Ltd. in Arlington, Virginia, respond to a letter providing further information on the association between oral contraceptives (OCs) and breast cancer. The letter refers to research revealing potential mechanisms through which some progestins, either with or without some estrogens, may bring on breast cancer. This basic research helps clarify confusing results of earlier epidemiologic studies and in designing future more optimal studies. For example, an intermediate growth factor or hormone (sex hormone-binding globulin, serum insulin-like growth factor I, or serum growth hormone) may be part of the causal pathway. Thus, researchers would need to actually measure this factor as well as the exogenous hormone to examine the link between OCs and breast cancer in large populations. A colleague misunderstood the staffers to believe that Demulen contains a high-potency progestagen, which research does not necessarily support. They did mention 2 studies which revealed a link between ethynodiol diacetate and breast cancer, but pointed out that the classification of progestins greatly weakened 1 study and that the methods used in most research to determine potency vary and are controversial. The same colleague misinterpreted the fact that the staffers presented some studies in their review, which used single numbers to classify the potency of combination OCs, as approval of this classification. They address the controversy of classifying potencies of progestins, but did not take the time to go into it deeply enough. They supported their colleague's belief that researchers should consider each progestin and combined OC as a separate exposure. They also agreed that researchers should obtain baseline information on endogenous hormone levels before administering the progestins or combined OCs to learn the different effect of the exposure between women. Language: English Keywords: CRITIQUE | ORAL CONTRACEPTIVES, COMBINED | BREAST CANCER | CONTRACEPTIVE AGENTS, PROGESTIN | ETHYNODIOL DIACETATE | RESEARCH METHODOLOGY | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Contraceptive Agents, Female | Contraceptive Agents Document Number: 079368 |
| 6. Peer Reviewed Title: Efficacy and safety of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms, with an emphasis on contraceptive efficacy. A phase IV trial. Author: Friedman AJ; Wheeler J Source: JOURNAL OF REPRODUCTIVE MEDICINE. 1991 Apr;36(4 Suppl):328-33. Abstract: From August 1988-June 1989, 983 physicians participated in a phase IV trial by following 7759 women using the monophasic oral contraceptive (OC), Demulen 1/35 (1 mg ethynodiol diacetate and 35 ug ethinyl estradiol) to evaluate its efficacy and safety. The total number of cycles for the study stood at 21,440. In addition, the total woman-years stood at 1787. Only 6382 patients could be evaluated for safety. 4.4% of the patients had adverse reactions to the OC, but only 1.7% of all patients stopped taking it. The leading side effects included nausea (67 cases), headache (45), amenorrhea (42), emotional changes (30), breast pain (19), dysmenorrhea (12), and 11 cases of weight gain, abdominal/pelvic pain, and bloating. Of the 280 reported adverse reactions, only 87 (31%) were considered severe. The leading serious adverse reactions were depression (10) and hypertension (6). Only 5412 patients could be used to determine efficacy. The physicians initially reported 121 (2.2%) pregnancies during the study. The researchers learned that 33 of the 84 returned 2nd questionnaires (response rate, 70%) reported that the women conceived after enrollment but before taking the OC. 36 conceived while taking it, but 8 did not take it daily. Noncompliance may have contributed to pregnancy for the remaining 28 cases. Therefore the 36 confirmed pregnancies made for a failure rate of .7%. 85.7% of the pregnancies happened in the 1st 3 months of taking the OC. Either patient noncompliance or true medication failure accounted for treatment failure. Therefore it is important for physicians to instruct patients on how to take OCs correctly. Language: English Keywords: UNITED STATES OF AMERICA | METHODOLOGICAL STUDIES | HUMAN VOLUNTEERS | PROSPECTIVE STUDIES | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES, PHASIC | CONTRACEPTIVE EFFECTIVENESS | CONTRACEPTION FAILURE | USER COMPLIANCE | OVARIAN CYSTS | CONTRAINDICATIONS | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | ORAL CONTRACEPTIVES, SIDE EFFECTS | WOMEN | Developed Countries | North America | Americas | Clinical Research | Research Methodology | Studies | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Oral Contraceptives, Combined | Oral Contraceptives | Contraceptive Methods | Contraceptive Usage | Behavior | Diseases | Treatment | Contraceptive Safety | Safety | Public Health | Health | Demographic Factors | Population Document Number: 066061 |
| 7. Peer Reviewed Title: Incidence of ovarian cyst formation in women taking ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms. Author: Friedman AJ; Wheeler JM Source: JOURNAL OF REPRODUCTIVE MEDICINE. 1991 Apr;36(4 Suppl):345-9. Abstract: A total of 7,759 women were treated with ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 mcg (EDA 1 mg with EE 35 mcg) in a field study involving 983 obstetrician-gynecologists evaluating the incidence of ovarian cyst formation. 6382 patients were evaluable; 1377 could not be evaluated because of failure to meet inclusion criteria or inconsistent or incomplete data collection. Cysts were detected in 80 patients at the time of the final visit. Follow-up questionnaires were received on 61% of patients and confirmed the presence of 12 newly formed ovarian cysts in patients taking EDA 1 mg with EE 35 mcg. Only 3 women required an operation for ovarian cysts; 2 women had functional ovarian cysts (1 follicular and 1 luteal), and 1 had neoplastic cyst (cystadenoma). Thus, the incidence of ovarian cyst formation requiring surgical intervention was 0.05% in women taking EDA 1 mg with EE 35 mcg. (author's) Language: English Keywords: RESEARCH REPORT | CLINICAL RESEARCH | ORAL CONTRACEPTIVES, LOW-DOSE | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | OVARIAN CYSTS | RISK ASSESSMENT | INCIDENCE | TREATMENT | LITERATURE REVIEW | HISTOLOGY | EXAMINATIONS AND DIAGNOSES | FOLLOW-UP STUDIES | SIDE EFFECTS | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Diseases | Evaluation | Measurement | Biology | Studies | Contraceptive Safety | Safety | Public Health | Health | Demographic Factors | Population Document Number: 066064 |
| 8. Peer Reviewed Title: Incidence of breakthrough bleeding during oral contraceptive therapy. Author: Hill GA; Wheeler JM Source: JOURNAL OF REPRODUCTIVE MEDICINE. 1991 Apr;36(4 Suppl):334-9. Abstract: A phase Iv, open-label, multicenter survey of 983 obstetrician-gynecologists was conducted to evaluate the incidence of intermenstrual bleeding in 6382 women receiving a low-dose monophasic oral contraceptive (OC), ethynodiol diacetate 1 mg along with ethinyl estradiol (EE) 35 mcg (EDA 1 mg with EE 35 mcg) over a 6-month period. Most patients (75%) did not experience intermenstrual bleeding during therapy. Followup questionnaires were sent to the physicians for the 1526 women reported breakthrough bleeding or spotting; 1027 followup questionnaires (67%) were returned. The questionnaires revealed that approximately 1/5 of the patients were placed on EDA 1 mg with EE 35 mcg to regulate preexisting bleeding. Of these, 71% reported an improvement, 13% reported a worsening, and 16% reported no change in their cycle regularity. Most breakthrough bleeding of spotting (91%) occurred in the 1st 3 months of therapy in women with preexisting irregular bleeding as well as in those using OCs solely for birth control. Although a fair number of women experienced intermenstrual bleeding, very few (5.1%) discontinued therapy because of it. Thus, the study demonstrated that the incidence of breakthrough bleeding and spotting appears to be within or below the range reported for other monophasic and multiphasic OCs. Further, in agreement with previously published reports, the data suggest that cycle control will improve after 3 months of OC use. (author's) Language: English Keywords: FOLLOW-UP STUDIES | ORAL CONTRACEPTIVES, LOW-DOSE | BLEEDING | INCIDENCE | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | LITERATURE REVIEW | UTERINE EFFECTS | CONTRACEPTION TERMINATION | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Signs and Symptoms | Diseases | Measurement | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology Document Number: 066060 |
| 9. 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 |
| 10. Peer Reviewed Title: Complexion changes in oral contraceptive users. Results from a phase IV multicenter trial evaluating the safety and efficacy of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms. Author: Wheeler JM; Malinak LR Source: JOURNAL OF REPRODUCTIVE MEDICINE. 1991 Apr;36(4 Suppl):340-4. Abstract: An open-label, phase IV, multicenter survey of obstetrician-gynecologists was conducted to investigate the efficacy and safety of a low-dose monophasic oral contraceptive (OC), ethynodiol diacetate, 1 mg, with ethinyl estradiol (EE), 35 mcg. Surveys from 983 community-based physicians reported on 6382 women, most of whom did not experience "clinically noticeable complexion changes" (5695/6382 or 89.2%). Of the 687 who did, nearly 3/4 reported an improvement (501/587 or 72.9%). A followup questionnaire was sent to 127 respondents (18.6%) who reported worsening of their complexions; 70% of the questionnaires were returned. Most had a slight degree of complexion worsening (63%) as reported by the patient and not the physician (84% vs 16%), and these changes were experienced during the 1st 2-3 months (84%). Although the literature includes many references to skin condition improvement while taking OCs, this report of a descriptive study gives clinicians an estimate of the incidence and severity of complexion changes during actual use. (author's modified). Language: English Keywords: SURVEYS | CLINICAL RESEARCH | ORAL CONTRACEPTIVES, LOW-DOSE | DERMATOLOGICAL EFFECTS | PHYSICIANS | ACNE | ETHINYL ESTRADIOL | ETHYNODIOL DIACETATE | SIDE EFFECTS | CHANGES | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Sampling Studies | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Physiology | Biology | Health Personnel | Delivery of Health Care | Health | Dermatitis | Diseases | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Treatment | Social Change | Contraceptive Safety | Safety | Public Health | Demographic Factors | Population Document Number: 066063 |
| 11. Peer Reviewed Title: Oral contraceptives, lipoproteins, and atherosclerosis. Author: Adams MR; Clarkson TB; Shively CA; Parks JS; Kaplan JR Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1990 Oct;163(4 Pt 2):1388-93. Abstract: A nonhuman primate model was developed to study the effects of oral contraceptives (OCs) on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The 1st study compared a vaginal ring containing levonorgestrel and estradiol with an OC containing norgestrel and ethinyl estradiol. A 2nd study compared 2 oral combinations: norgestrel/ethinyl estradiol and ethynodiol diacetate/ethinyl estradiol. As predicted, use of all the contraceptives led to a lowering of high- density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing OCs did not lead to an increase in the prevalence or extent of atherosclerosis. The authors concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of OCs. (author's) Language: English Keywords: LABORATORY ANIMALS | LIPID METABOLIC EFFECTS | ATHEROSCLEROSIS | VAGINAL RING | LEVONORGESTREL | ETHINYL ESTRADIOL | NORGESTREL | ETHYNODIOL DIACETATE | ORAL CONTRACEPTIVES, COMBINED | FEMALE CONTRACEPTION | CHANGES | ADMINISTRATION AND DOSAGE | ANALYSIS | Clinical Research | Research Methodology | Lipids | Physiology | Biology | Arteriosclerosis | Arterial Occlusive Diseases | Vascular Diseases | Diseases | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Oral Contraceptives | Social Change | Drugs | Treatment Document Number: 063848 |
| 12. Peer Reviewed Title: The efficacy of the progestogen-only pill as a contraceptive method. Author: Bisset AM; Dingwall-Fordyce I; Hamilton MI Source: British Journal of Family Planning. 1990 Oct;16(3):84-7. Abstract: For more than a decade, it has been stated that the progestogen-only pill (POP) is an underused method of contraception. The experience at the Aberdeen Central Family Planning Clinic with POPs currently available in the United Kingdom was investigated in a retrospective study. 1042 cases with a mean exposure of 24 months (interquartile range 5-29 months) formed the study population. This paper assessed the efficacy of the method and is part of a larger study assessing method acceptability and continuation rate for POPs. The Pearl Index (PI) of the method for all ages was found to be 1.01; adjusted for patient failure, the corrected PI was 0.43. The range of PI according to age was from 0.0 (ages under 25 and over 45) to 0.78 (ages 25-34). For a single center with consistent counselling, the efficacy of the POP as a contraceptive is approaching that of the combined pill. In view of these findings, the authors would encourage greater use of the progestogen-only pills in all age groups. (author's) Language: English Keywords: UNITED KINGDOM | RETROSPECTIVE STUDIES | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTIVE METHOD ACCEPTABILITY | AGE DISTRIBUTION | PEARL'S FORMULA | ETHYNODIOL DIACETATE | NORETHINDRONE | NORGESTREL | LEVONORGESTREL | PREGNANCY RATE | PREGNANCY, ECTOPIC | CONTRACEPTION FAILURE | CONTRACEPTIVE USAGE | FAMILY PLANNING PROGRAM EVALUATION | COUNSELING | Developed Countries | Europe, Western | Europe | Studies | Research Methodology | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Age Factors | Population Characteristics | Demographic Factors | Population | Contraceptive Use-Effectiveness | Contraceptive Effectiveness | Fertility Measurements | Fertility | Population Dynamics | Pregnancy Complications | Diseases | Family Planning Programs | Clinic Activities | Program Activities | Programs | Organization and Administration Document Number: 064036 |
| 13. Peer Reviewed Title: Clinical experience with the progestogen-only pill. Author: Broome M; Fotherby K Source: CONTRACEPTION. 1990 Nov;42(5):489-95. Abstract: Experience with the progestogen-only pill (POP) in a family planning clinic is presented. From the clinic records, 408 women were identified who had opted to use a POP. Of these, 50 women had used the POP during lactation and these were excluded from the analysis. The remaining 358 women used the POP for up to 150 months, giving a total of 18,125 women- months or use. 3 pregnancies occurred, giving a Pearl Index of 0.2/100 women-years. Nonmenstrual side effects were minor and were reported by 77 women. For the women who discontinued the POP, the main reason was menstrual irregularity (47.5%). However, despite the longterm use by most of the women, almost 40% maintained a mostly regular menstrual pattern. The findings suggest that the POP provides a very acceptable method of oral contraception for many women and that it should be more actively promoted. (author's) Language: English Keywords: UNITED KINGDOM | FAMILY PLANNING CENTERS | LEVONORGESTREL | NORETHINDRONE | ETHYNODIOL DIACETATE | CONTRACEPTION TERMINATION | POPULATION CHARACTERISTICS | CONTRACEPTIVE AGENTS, PROGESTIN | BLEEDING | CONTRACEPTIVE METHOD ACCEPTABILITY | MENSTRUATION DISORDERS | EVALUATION | ORAL CONTRACEPTIVES | FEMALE CONTRACEPTION | CLINICAL RESEARCH | ADMINISTRATION AND DOSAGE | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | United Kingdom | Europe, Western | Europe | Developed Countries | Health Facilities | Delivery of Health Care | Health | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Demographic Factors | Population | Signs and Symptoms | Diseases | Contraceptive Usage | Contraceptive Methods | Research Methodology | Drugs | Treatment Document Number: 064016 |
| 14. Title: Oral contraceptives and cardiovascular risk. Taking a safe course of action. Author: Derman RJ Source: POSTGRADUATE MEDICINE. 1990 Sep 15;88(4):119-22. Abstract: The cardiovascular effects of oral contraceptives, as predicted by studies on serum lipid changes in users, are based on the progestin dose, androgenic potency and biologic effect of the estrogen in the pill. Women suffer 250,000 deaths per year in the U.S. resulting from cardiovascular disease, almost half as many as men. They have the same risk factors: high cholesterol, high blood pressure and smoking, and also have more risk from diabetes than men do. The serum HDL, especially HDL2, correlates closely and inversely with heart disease risk. Exogenous estrogens raise HDL and HDL2, and lower LDL, conferring protection against coronary disease, in direct proportion to dose. Progestins usually have adverse effects, in proportion to dose, but progestin potency and type also determine their effects. The estrane progestins norethindrone, norethindrone acetate and ethynodiol diacetate are less potent and much less androgenic, while the gonanes norgestrel and especially levonorgestrel are 5-20 times as potent and androgenic. Each pill needs to be considered as a unit. Several comparative studies are reviewed, corroborating the prediction that pills with higher progestin potency have adverse effects on serum lipids, compared to those with higher estrogen effect. For new lower dose multiphasics, the effects either way are minimal, but HDL2 is still significantly lowered by pills containing levonorgestrel. Progestin-only pills lower HDL2 17- 21%. It is prudent to follow and treat the long-term effects of oral contraceptives on blood lipids. Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | CONTRACEPTIVE AGENTS, PROGESTIN | ETHINYL ESTRADIOL | LEVONORGESTREL | NORGESTREL | NORETHINDRONE | NORETHINDRONE ACETATE | ETHYNODIOL DIACETATE | HEART DISEASES | MYOCARDIAL INFARCTION | LIPID METABOLIC EFFECTS | RISK FACTORS | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | Developed Countries | North America | Americas | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Diseases | Lipids | Physiology | Biology | Oral Contraceptives | Contraceptive Methods Document Number: 064008 |
| 15. Peer Reviewed Title: The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. Author: Godsland IF; Crook D; Simpson R; Proudler T; Felton C; Lees B; Anyaoku V; Devenport M; Wynn V Source: NEW ENGLAND JOURNAL OF MEDICINE. 1990 Nov 15;323(20):1375-81. Abstract: Oral contraceptives (OCs) can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low- density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, the authors examined whether modification of the type or dose of progestin in OC preparations diminishes these changes. They measured plasma lipoprotein levels and performed oral glucose tolerance tests in a cross-section of 1060 women who took 1 of 9 types of OCs for at least 3 months and 418 women who took none. 7 of the OC formulations contained various doses and types of progestin: levonorgestrel in low (150 mcg), high (250 mcg), and triphasic (50-125 mcg) doses; norethindrone in low (500 mcg), high (1000 mcg), and triphasic (500-1000 mcg) doses; and a new progestin, desogestrel, in 1 150 mcg dose. All 7 contained 30-40 mcg ethinyl estradiol. 2 additional formulations contained progestin alone. As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13-75% in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14% in women taking the desogestrel combination and by 12% in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5% and 16% by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29% and 43% respectively; in the levels of HDl subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10%. The desogestrel combination increased HDL cholesterol levels by 12%. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose tolerance test that were 43-61% higher than in controls, insulin responses 12-40% higher, and C-peptide responses 18-45% higher. Progestin-only formulations had only minor metabolic effects. The appropriate dose and type of progestin may reduce the adverse effects of OCs on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated with the most favorable profiles. (author's) Language: English Keywords: UNITED KINGDOM | LIPID METABOLIC EFFECTS | CARBOHYDRATE METABOLIC EFFECTS | RISK FACTORS | LABORATORY EXAMINATIONS AND DIAGNOSES | LEVONORGESTREL | NORETHINDRONE | ETHYNODIOL DIACETATE | DESOGESTREL | GLUCOSE TOLERANCE TEST | CARDIOVASCULAR EFFECTS | ORAL CONTRACEPTIVES, COMBINED | COMPARATIVE STUDIES | ANALYSIS | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | United Kingdom | Europe, Western | Europe | Developed Countries | Lipids | Physiology | Biology | Metabolic Effects | Examinations and Diagnoses | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Laboratory Procedures | Oral Contraceptives | Contraceptive Methods | Studies | Research Methodology | Treatment | Demographic Factors | Population Document Number: 064243 |
| 16. Title: Pharmacokinetics of oestrogens and progestogens. Author: Kuhl H Source: MATURITAS. 1990 Sep;12(3):171-97. Abstract: There are large inter- and intraindividual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral intake of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the 1st liver passage. Estradiol and estrone are interconvertible, dependent on the local concentrations in liver and target organs, and estrone sulphate serves as a large reservoir. The estrone/estradiol ratio has no physiological significance, as estrone is only a weak estrogen. Estrone is both a precursor and a metabolite of estradiol. Estriol is extensively conjugated after oral administration. Therefore, the estriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg estriol resulting in similar systemic effectiveness. Conjugated estrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinyl estradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group. (author's) Language: English Keywords: ESTROGENS | PROGESTERONE | ESTRADIOL | ESTRONE | ESTRIOL | MEASUREMENT | STEROID METABOLIC EFFECTS | LABORATORY EXAMINATIONS AND DIAGNOSES | ETHINYL ESTRADIOL | LEVONORGESTREL | ETHYNODIOL DIACETATE | LYNESTRENOL | NORETHINDRONE | CYPROTERONE ACETATE | CHLORMADINONE ACETATE | NORETHINDRONE ACETATE | ANALYSIS | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Research Methodology | Metabolic Effects | Examinations and Diagnoses | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Hormone Antagonists Document Number: 064558 |
| 17. Title: The treatment of hyperandrogenism with oral contraceptives. Author: Azziz R; Gay F Source: SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY. 1989 Aug;7(3):246-54. Abstract: Oral contraceptives are usually effective, simple and inexpensive for treatment of women with hyperandrogenism. Hyperandrogenism is usually caused by ovarian overproduction of testosterone, androstenedione or dehydroepiandrosterone-sulfate, due to high LH overstimulating the thecal cells. Androgens can be elevated from adrenal hyperplasia, Cushings disease or tumors. Failing that, "idiopathic hirsutism" can be a result of overactive 5alpha-reductase in skin. Oral contraceptives work by suppressing LH and FSH in a dose-dependent manner, reducing steroid release by ovaries; decreasing free testosterone by raising levels of sex-hormone-binding globulin; reducing adrenal androgen production by an unknown mechanism; and inhibiting skin 5alpha-reductase by competition with progestins. Improvement is reported in 60-100% of women, usually within 2 cycles. The most dramatic improvement is cessation of new hair growth. Old hairs may become thinner, but will need to be removed by electrolysis, Orals regulate withdrawal bleeding, and acne and oily skin usually improve. Auxiliary treatments are low dose tetracycline, spironolactone, low dose glucocorticoid and androgen antagonists such as cyproterone acetate. Language: English Keywords: LITERATURE REVIEW | ANDROGENS | CYPROTERONE ACETATE | ADRENAL CORTEX HORMONES | LUTEINIZING HORMONE | ETHYNODIOL DIACETATE | ACNE | HIRSUTISM | AMENORRHEA | OBESITY | GLUCOSE METABOLISM EFFECTS | ORAL CONTRACEPTIVES, COMBINED | ETHINYL ESTRADIOL | Hormones | Endocrine System | Physiology | Biology | Hormone Antagonists | Gonadotropins, Pituitary | Gonadotropins | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Dermatitis | Diseases | Signs and Symptoms | Menstruation Disorders | Body Weight | Carbohydrate Metabolic Effects | Metabolic Effects | Oral Contraceptives | Contraceptive Methods | Contraceptive Agents, Estrogen Document Number: 064713 |
| 18. 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 |
| 19. Title: The progestogen-only pill and thrombosis. Author: Fotherby K Source: British Journal of Family Planning. 1989 Oct;15(3):83-5. Abstract: Many studies have shown that combined oral contraceptives (COC) may produce changes in the concentration or activity of most hematological factors. In contrast, limited studies of the progestogen-only pill (POP) suggest that it causes little change. The published data for the POP are summarized in a table. Other studies are also relevant, eg no change was observed in a large number of hematological factors when norethisterone or LNG was administered orally in doses greater than those used in the POP. When changes in hematological factors do occur in women using contraceptive steroids and are of a magnitude indicative of a hypercoagulable state, there is no evidence that this will necessarily lead to thrombosis. It could be postulated that it may do so in women who have a disposition form thrombotic events but again, evidence to support such a hypothesis is lacking. Despite the number of epidemiological studies which have been performed it is still controversial whether, and to what extent, even use of COC's increases the incidence of cardiovascular disease. In the Oxford-FPA study involving 3303 woman-years of observation, 4 women developed cardiovascular disorders but it is not possible from the information presented to determine whether this is more or less than expected. A recent study reported changes in a number of hematological factors in women who had been using LNG subdermal implants (Norplant) for 1 year. The changes, however, were small, even for those factors which showed a statistically significant change, and are unlikely to be of clinical significance. These findings are at variance with those from other studies. The pathogenesis of venous and arterial thrombi are probably different and hematological factors are only 1 of many components involved in thrombus formation. (Author). Language: English Keywords: ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, PROGESTIN | THROMBOSIS | LITERATURE REVIEW | NORETHINDRONE | LEVONORGESTREL | CONTRACEPTIVE AGENTS, FEMALE | ETHYNODIOL DIACETATE | ETHINYL ESTRADIOL | HEMATOLOGICAL EFFECTS | CONTRACEPTIVE IMPLANTS | CLINICAL RESEARCH | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents | Thromboembolism | Embolism | Vascular Diseases | Diseases | Contraceptive Agents, Estrogen | Hemic System | Physiology | Biology | Research Methodology Document Number: 271620 |
| 20. Title: Choosing the best oral contraceptive. Author: Stubblefield PG Source: CLINICAL OBSTETRICS AND GYNECOLOGY. 1989 Jun;32(2):316-28. Abstract: This guide to choice of oral contraceptives, for U.S. clinicians, includes a review of the available types of pills, the pharmacology of the steroids in pills, safety issues regarding thrombosis, arterial disease and hypertension related to estrogens and progestins in pills, common side effects, and therapeutic uses of orals. Choice of an oral contraceptive narrows down to which of the 5 available progestins and their formulation, since all contain ethinyl estradiol as the estrogen. While Briggs' theory espoused picking a pill with the minimal metabolic effect, recent evidence suggests that some estrogenic activity may be preferable to the unopposed progestagen, actually an anti-estrogenic receptor effect, to prevent adverse lipid and blood pressure effects in users. Current pills with low doses of estrogens probably are not significant risks for women as regards thrombosis, particularly if predisposed women and smokers are excluded. Pills containing 0.35 mg ethinyl estradiol and 0.5 mg norethindrone, based on large population trials, are probably the minimal effective dose yet even these are more effective than most other contraceptive methods. Breakthrough bleeding and spotting have been further minimized, however, with multiphasic pills. It is best to start with a 0.30-0.35 mg estrogen oral contraceptive, such as Loestrin, Demulin, Orthonovum 1.35, Orthonovum 7/7/7 or Nordette, encouraging the patient to accept early side effects for 3 months before switching to others. Disorders that can be managed with oral contraceptives include recurring and pre-existing ovarian cysts, endometriosis, dysfunctional uterine bleeding and dysmenorrhea. Brief guidelines for handling normal side effects and treatment of the above disorders are included. Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | NORETHINDRONE | NORETHINDRONE ACETATE | LEVONORGESTREL | NORGESTREL | ETHYNODIOL DIACETATE | CONTRACEPTIVE AGENTS, FEMALE | ARTERIAL OCCLUSIVE DISEASES | HYPERTENSION | THROMBOEMBOLISM | LIPID METABOLIC EFFECTS | SIGNS AND SYMPTOMS | OVARIAN CYSTS | ENDOMETRIAL EFFECTS | DYSMENORRHEA | Developed Countries | North America | Americas | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents | Contraceptive Agents, Progestin | Vascular Diseases | Diseases | Embolism | Lipids | Physiology | Biology | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Menstruation Disorders Document Number: 060667 |
| 21. Title: Carbohydrate and lipid metabolism in low-dose oral contraception. Author: Wynn V; Godsland I; Simpson R; Lees B; Proudler T; Felton C; Anyoku V; Crook D Source: In: Fertility, sterility and contraception, edited by P. Belfort, J.A. Pinotti and T.K.A.B. Eskes. Carnforth, England, Parthenon Publishing Group, 1989. :287-98. (Advances in Gynecology and Obstetrics Series Vol. 1) Proceedings of the 12th World Congress of Gynecology and Obstetrics, Rio de Janeiro, October 1988. Abstract: In a cross sectional study, women taking low-dose oral contraceptives with constant dose of estrogen, 30-40 mcg ethinyl estradiol, and various progestin formulations, either levonorgestrel (LG), norethindrone (NE), desogestrel (DG) or ethynodiol diacetate (ED), were compared with respect to lipid and glucose tolerance 3 months or more. Subjects had a glucose tolerance test with measurement of insulin and C-peptide on menstrual cycle Day 21-27 or pill cycle Day 17-21. Groups were matched for smoking, alcohol use, exercise, parity, and family history of diabetes or heart disease. All pills tended to lower fasting glucose and increase insulin, C-peptide and incremental glucose area, the fixed dose LG pill being most active. Combined pills increased triglycerides. Fixed dose NE and DG reduced LDL. The fixed dose and triphasic LG pills significantly increased apo B, the protein in LDL. 2 fixed-dose LG pills and high fixed dose NE pills reduced HDL. Low fixed dose NE and DG pills increased HDL. All combined pills increased apo A1, the major protein in HDL, except high fixed dose LG pills, which lowered apo A1. HDL2/LDL ratio was reduced by all LG pills and the high fixed dose NE pill. NE progestagen only pills reduced HDL and HDL2. The results were interpreted in the discussion in terms of the estrogen androgen balance of the pills. Ranking pills by HDL2/LDL ratio as an indicator of lipid status, resembled their ranking by carbohydrate metabolic impact. The DG and NE pills had least adverse effects, the LG triphasic has moderate impact, and the combined LG pills had the most adverse impact on both lipid and carbohydrate status. Language: English Keywords: UNITED KINGDOM | COMPARATIVE STUDIES | MATCHED GROUPS | CONTROL GROUPS | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | ETHINYL ESTRADIOL | LEVONORGESTREL | CONTRACEPTIVE AGENTS, FEMALE | NORETHINDRONE | ETHYNODIOL DIACETATE | CARBOHYDRATE METABOLIC EFFECTS | GLUCOSE METABOLISM EFFECTS | LIPID METABOLIC EFFECTS | United Kingdom | Europe, Western | Europe | Developed Countries | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents | Contraceptive Agents, Progestin | Metabolic Effects | Physiology | Biology | Lipids Document Number: 058791 |
| 22. Title: Effect of administration and withdrawal of oral contraceptive pills on serum lipids and lipoproteins. Author: Arora S; Arora RC; Garg RK; Agarwal N; Nautiyal A Source: INDIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY. 1988 Jan-Mar;32(1):67-71. Abstract: Studies on the use of oral contraceptives in the West have shown that they induce changes in total serum cholesterol, triglycerides, high density lipoproteins, low density lipoproteins, and very low density lipoproteins -- changes which are implicated in the development of atherosclerosis. In India, however, women consume low fats, low cholesterol and fewer calories; they drink less alcohol and rarely smoke; and they engage in more physical activities. 2 groups of Indian women were tested for lipid metabolism alterations during and after use of oral contraceptives supplied by the Indian government. 1 group of 23 women, aged 20-30, received low dose oral contraceptives containing 30 ug ethinyl estradiol and 1 mg of norethisterone acetate, and their serum lipid levels were tested after 3 and 6 months of use. A 2nd group of 12 multiparas, aged 25-35, who had been taking oral contraceptives for 1 1/2 to 2 years (either 50 um ethinyl estradiol and .5 mg norgestrel, called Ovular or Primovlar-50, or 30 ug ethinyl estradiol and .5 mg ethynodiol diacetate, called Ovular-50) were examined for serum lipid levels 3 and 6 months after withdrawal from the pills. In the 1st group no significant change was observed in any lipid fraction after 3 or 6 months of oral contraceptive use. In the 2nd group low density lipoprotein levels were significantly lower 3 and 6 months after withdrawal, in comparison with the basal values of the 1st group. It is concluded that low dose oral contraceptives supplied by the Indian government have no significant effect on serum lipids after 6 months of use. Language: English Keywords: INDIA | LIPID METABOLIC EFFECTS | STEROID METABOLIC EFFECTS | LIPIDS | CHOLESTEROL | ATHEROSCLEROSIS | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | ETHYNODIOL DIACETATE | NORETHINDRONE ACETATE | NORGESTREL | Asia, Southern | Asia | Developing Countries | Physiology | Biology | Metabolic Effects | Arteriosclerosis | Arterial Occlusive Diseases | Vascular Diseases | Diseases | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Norethindrone Document Number: 055801 |
| 23. Peer Reviewed Title: Lipid and lipoprotein changes associated with oral contraceptive use: a randomized clinical trial. Author: Burkman RT; Robinson JC; Kruszon-Moran D; Kimball AW; Kwiterovich P; Burford RG Source: OBSTETRICS AND GYNECOLOGY. 1988 Jan;71(1):33-8. Abstract: To determine the effects of oral contraceptives (OCS) on lipids and lipoproteins over a 6-month period, the authors randomized 266 women into 4 groups--1) ethinyl estradiol 35 mcg + ethynodiol diacetate 1 mg; 2) ethinyl estradiol 30 mcg + levonorgestrel 0.15 mg; 3) ethinyl estradiol 35 mcg + norethindrone 1 mg; and 4) ethinyl estradiol 35 mcg + norethindrone 0.5 and 1 mg (biphasic). For all groups, total cholesterol increased 5.9-9.1% from baseline values over the 6 months. Triglycerides increased with all preparations, with the ethynodiol diacetate group (37.6%) and the biphasic norethindrone group (45.3%) showing the greatest increase. Low density lipoprotein (LDL) cholesterol increased 10-15.6% among the groups; LDL-apolipoprotein B changed proportionally to the LDL cholesterol increases. All groups except the ethynodiol diacetate group showed a decrease of HDL cholesterol, with the levonorgestrel group (8.7%) and biphasic norethindrone group (4.5%) showing the largest declines. Apolipoprotein A-1 increased in all groups, with the ethynodiol diacetate preparation (19.3%) showing the greatest increase and the levonorgestrel preparation (3.2%) showing the smallest increase from baseline values. The changes in apolipoprotein A-1 were out of proportion to the changes in HDL cholesterol, suggesting that the HDL particle may be undergoing some type of metabolic alteration. (author's) Language: English Keywords: CLINICAL RESEARCH | RESEARCH METHODOLOGY | ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | LIPID METABOLIC EFFECTS | METABOLIC EFFECTS | DATA COLLECTION | LABORATORY EXAMINATIONS AND DIAGNOSES | EXAMINATIONS AND DIAGNOSES | POPULATION CHARACTERISTICS | DATA ANALYSIS | CHANGES | ETHINYL ESTRADIOL | NORETHINDRONE | LEVONORGESTREL | ETHYNODIOL DIACETATE | HORMONES | REPRODUCTIVE CONTROL AGENTS | BLOOD PRESSURE | POPULATION AT RISK | CARDIOVASCULAR EFFECTS | Contraceptive Methods | Family Planning | Contraceptive Agents | Lipids | Physiology | Biology | Demographic Factors | Population | Social Change | Contraceptive Agents, Estrogen | Contraceptive Agents, Progestin | Endocrine System | Hemic System Document Number: 046931 |
| 24. 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 |
| 25. Peer Reviewed Title: The varying effects of progestins on lipid levels and cardiovascular disease. Author: La Rosa JC Source: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. 1988 Jun;158(6 Pt 2):1621-9. Abstract: A recent study at George Washington University Lipid Research Clinic compared 3 oral contraceptives (OCs) containing different progestins and found that increases in total cholesterol, triglycerides, and apoprotein. All were not progestin related. Other effects, however, were apparently dependent on the type of progestin, with the androgenically potent agent dl-norgestrel causing dramatic increases in low-density lipoprotein (LDL)-cholesterol and the ratio of LDL to HDL and decreases in HDL, particularly HDL2, and apoprotein A1. Reductions in HDL2 and increases in the LDL/HDL ratio are strongly associated with the development of atherosclerosis. In a study of postmenopausal women receiving hormone replacement therapy, estrogen alone was compared with estrogen plus dl-norgestrel. In contrast to the findings of the previous study, norgestrel lowered LDL and produced less substantial decreases in HDL and HDL2. Thus, although an antiestrogenic effect was evident, it cannot be assumed that the changes associated with progestin-containing OCs will automatically occur when lower doses of progestin are used in hormone replacement therapy. (author's) Language: English Keywords: DISTRICT OF COLUMBIA | LIPID METABOLIC EFFECTS | CONTRACEPTIVE AGENTS, PROGESTIN | CONTROL GROUPS | ETHINYL ESTRADIOL | CONTRACEPTIVE AGENTS, FEMALE | NORETHINDRONE ACETATE | ETHYNODIOL DIACETATE | HEART DISEASES | HORMONES | CARDIOVASCULAR EFFECTS | UNITED STATES OF AMERICA | CHANGES | ADMINISTRATION AND DOSAGE | PREVENTION AND CONTROL | Developed Countries | North America | Americas | Lipids | Physiology | Biology | Contraceptive Agents | Contraception | Family Planning | Research Methodology | Contraceptive Agents, Estrogen | Norethindrone | Diseases | Endocrine System | Social Change | Drugs | Treatment Document Number: 058987 |
| 26. Title: Estrogen dose-response relationship [letter] Author: Edgren RA Source: CLINICAL PHARMACOLOGY AND THERAPEUTICS. 1987 May;41(5):587. Abstract: This letter criticizes a report on the increased relative risk of developing gall bladder disease with increasing dose exposure to the estrogens in oral contraceptives. The chief objection is the assumption that the risk is said to apply to mere dose of estrogen, without acknowledging that 2 different estrogens of different potency on various target organs were ingested since 1980. From 1980 to 1980, pills with over 50 mg estrogen contained mestranol, while later pills of lower dose contained ethinyl estradiol (EE). Furthermore, the effect of estrogens is modified by the type and dose of the progestin used in the combination. Five different progestins were used during the period: norethindrone (with mestranol or EE), northynodrel (with mestranol), ethynodiol diacetate (with either estrogen), and norethindrone acetate and norgestrel (with EE). Norethindrone and norgestrel as such, while the others are metabolized to various degrees to norethindrone. Thus, the dose-response relationship between estrogen and gall bladder disease cannot be supported by the data presented. Language: English Keywords: CALIFORNIA | UNITED STATES OF AMERICA | NORTH AMERICA | FAMILY PLANNING | CONTRACEPTION | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTIVE AGENTS, ESTROGEN | ORAL CONTRACEPTIVES, SIDE EFFECTS | ORAL CONTRACEPTIVES, COMBINED | REPRODUCTIVE CONTROL AGENTS | HORMONES | ETHINYL ESTRADIOL | MESTRANOL | ETHYNODIOL DIACETATE | NORETHINDRONE | NORETHYNODREL | BILIARY TRACT DISEASES | GALLBLADDER DISEASES | RESEARCH METHODOLOGY | DISEASES | SIDE EFFECTS | Developed Countries | Americas | Contraceptive Agents | Contraceptive Safety | Safety | Public Health | Health | Oral Contraceptives | Contraceptive Methods | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Treatment Document Number: 044584 |
| 27. Title: [Progestagens as contraceptives] Progestagene zur Empfangnisverhutung. Author: Kuhl H Source: WIENER MEDIZINISCHE WOCHENSCHRIFT. 1987;137(18-19):433-40. Abstract: The different spectrum of biological actions of the various synthetic progestogens is compared on the basis of chemical structure, pharmacokinetics, and interaction with the multiple receptors. The mechanism of action of the progesterone derivatives (medroxyprogesterone acetate, chlormadinone acetate, and cyproterone acetate), the norethisterone-related (norethisterone, ethynodiol diacetate, lynestrenol, and norethynodrel), and the norgestrel-related progestogens (levonorgestrel, desogestrel, gestodene, and norgestimate), and a possible influence of some metabolites on the biological profile are discussed. With regard to progestogenic activity, the time course of the serum concentrations of the steroids after the application (pharmacokinetics) which is dependent on absorption, metabolization in the gastrointestinal tract and liver (1st-pass effect), distribution and storage in fat and other tissues, binding to serum proteins, inactivation, and conjugation is of particular importance. The various side effects of the progestogens are based mainly on their influence on hepatic metabolism (lipids, lipoproteins, serum proteins) and upon other organs which influence their estrogenic, antiestrogenic, androgenic, antiandrogenic, glucocorticoid, and antimineralocorticoid actions. (author's modified) (summaries in ENG, GER) Language: German Keywords: HORMONES | REPRODUCTIVE CONTROL AGENTS | STEROID METABOLIC EFFECTS | METABOLIC EFFECTS | LIPID METABOLIC EFFECTS | SIDE EFFECTS | ANALYSIS | MEDROXYPROGESTERONE ACETATE | CHLORMADINONE ACETATE | CYPROTERONE ACETATE | NORETHINDRONE | LYNESTRENOL | ETHYNODIOL DIACETATE | NORETHYNODREL | LEVONORGESTREL | Endocrine System | Physiology | Biology | Family Planning | Lipids | Treatment | Research Methodology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Hormone Antagonists Document Number: 051407 |
| 28. Title: Oral contraceptives and breast cancer. In vitro effect of contraceptive steroids on human mammary cell growth. Author: Longman SM; Buehring GC Source: CANCER. 1987 Jan 15;59(2):281-7. Abstract: The growth responses were measured of human mammary epithelial cells, from 59 normal, nonmalignant atypical and malignant breast specimens, in tissue culture with oral contraceptive steroids. The steroid levels, 0.1 mcg/ml for estrogens and 1.0 mcg/ml for progestins, were taken from dose response curves so that the lowest steroid doses found to stimulate maximum growth in control cell lines were chosen. These concentrations were 3 times the serum estrogen level and 4 times the progesterone level of late pregnancy. Growth was assessed by daily area measurements of cells attached to culture vessels, known to be proportional to cell numbers, and expressed either as proportion of stimulated cultures or as doubling times. Stimulated growth was highly individual, especially in response to progestins. Growth was generally stimulated by ethinyl estradiol alone and in combination, and by 17B-estradiol, but not by mestranol. Most (75%) of the malignant cultures responded to at least 1 progestin, but nonmalignant cells usually did not. The progestins progesterone, norethindrone, norgestrel and norethinodrel stimulated most of the malignant cultures. Ethynodiol diacetate was less active, and mestranol inhibited growth of 1 specimen. Proliferative response to estrogens was rather well correlated with presence of estrogen receptor, but that to progestins was unrelated to progesterone receptor. Malignant cells grew faster than nonmalignant cells from the same subject in the presence of 2 combinations: ethinyl estradiol/norgestrel and mestranol/norethindrone. This study demonstrated the ability of progestins alone to stimulate neoplastic cell growth, in some cases more rapidly than normal tissue. This opens the possibility that oral contraceptive steroids could act as cancer promoters, selectively stimulating the growth of a few previously transformed cancer cells. The relationship of the highly individualized and heterogeneous responses seen here to actual cells growing in vivo is unknown. Language: English Keywords: FAMILY PLANNING | CONTRACEPTION | CONTRACEPTIVE AGENTS, FEMALE | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, ESTROGEN | CONTRACEPTIVE AGENTS, PROGESTIN | HORMONES | ETHINYL ESTRADIOL | MESTRANOL | NORETHINDRONE | NORGESTREL | NORETHYNODREL | ETHYNODIOL DIACETATE | CORPUS LUTEUM HORMONES | PROGESTERONE | ESTROGENS | ESTRADIOL | NEOPLASMS | CANCER | BREAST CANCER | HORMONE RECEPTORS | PHYSIOLOGY | GROWTH | RESEARCH METHODOLOGY | RESEARCH AND DEVELOPMENT | IN VITRO | CALIFORNIA | Contraceptive Agents | Contraceptive Methods | Endocrine System | Biology | Progestational Hormones | Diseases | Membrane Proteins | Child Development | Technology | Economic Factors | Clinical Research | Developed Countries | United States of America | North America | Americas Document Number: 045164 |
| 29. Title: Endocrine effects of systemic, steroidal contraceptives. Author: Edgren RA Source: In: Contraceptive steroids: pharmacology and safety, edited by A.T. Gregoire and Richard P. Blye. New York, New York, Plenum, 1986. :163-78. Abstract: Researchers have been able to predict clinical effects of systemic, steroidal contraceptives based on animal models. They cannot accurately predict, however, what quantities are appropriate for humans. Therefore, scientists should depend on human data to identify the optimum dose. Estrogens bind to cytoplasmic receptors in laboratory animals which cause several effects including prevention of uterine growth, particularly the preovulatory endometrium,; control of cyclic changes in the vagina; and regulation of the menstrual cycle. When estrogens are administered simultaneously with progestagens, however, the estrogenic induced uterine and vaginal effects do not appear. Most progestagens bind to the endometrial progesterone receptor, except those that are derivatives of 19-nortestosterone. Further, some bind to the testosterone receptor and produce androgenic effects. Progestational effects consist of secretory change of the uterus, delay of menstruation, and efficacy as an oral contraceptive when combined with estrogen. The progestogen, medroxyprogesterone acetate, binds to the glucocorticoid receptor. Toxicological tests indicate clinical corticoid action, such as deterioration of the adrenal gland. These effects have not yet appeared in Depo Provera users, however. Recommendations for preclinical criteria include not changing present requirements for endocrine studies and pharmacological and clinical effects, allow field trials after 6 months of toxicity studies in 2 species, narrow toxicity criteria to those established for other classes of drugs, and no longer require the 7 year dog and 10 year monkey studies which test for tumor development. Language: English Keywords: UNITED STATES OF AMERICA | CALIFORNIA | GOVERNMENT AGENCIES | |