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A prospective study of reproductive factors and oral contraceptive use in relation to the risk of uterine leiomyomata.

OBJECTIVE: To investigate the risk of uterine leiomyomata in relation to reproductive factors and oral contraceptive use. DESIGN: A prospective study. SETTING: A cohort of female registered nurses from 14 states in the United States who completed mailed questionnaires in 1989, 1991, and 1993. PATIENT(S): Premenopausal nurses (n=95,061) aged 25-42 years with intact uteri and no history of diagnosed uterine leiomyomata or cancer in 1989. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of self-reported uterine leiomyomata confirmed by ultrasound or hysterectomy. In a sample of 243 cases, 93% of the self-reported diagnoses were confirmed in the medical record. RESULT(S): During 326,116 person-years of follow-up, 3,006 cases of uterine leiomyomata, confirmed by ultrasound or hysterectomy, were reported. After adjustment for other risk factors, the risk of uterine leiomyomata was significantly inversely associated with age at menarche, parity, and age at first birth, and positively associated with a history of infertility and years since last birth. The only notable association with any aspect of oral contraceptive use was a significantly elevated risk among women who first used oral contraceptives at ages 13-16 years compared with those who had never used oral contraceptives. CONCLUSION(S): Reproductive factors and oral contraceptive use at a young age influence the risk of uterine leiomyomata among premenopausal women.

Adult↗

Calcium and phosphorus in milk of Brazilian mothers using oral contraceptives.

OBJECTIVE: Oral contraceptives (OC) are the most efficient method of contraception and it is the most prescribed by doctors in developing countries. Therefore we studied the effects of combination pill and mini-pill on calcium and phosphorus in milk of breast-feeding mothers at different stages of lactation. METHODS: Fifty-four breast-feeding mothers made up three study groups: 33 mothers who had been advised by their doctors to use either combination pill (12), or mini-pill (21), as well as a control group of 21 mothers that used no hormonal contraceptives. All mothers completed a questionnaire and provided samples of milk before and after a measured period of observation. Mean duration of study was 76, 120, and 101 days, respectively for users of mini-pill, combination pill, and controls. Determination of calcium and phosphorus was done by inductively coupled plasma-atomic absorption spectrometry. RESULTS: Overall the decrease in milk concentrations of phosphorus (6%) and calcium (26.3%) during the study period was not influenced by OC treatment. Regression analyses which took into consideration length of treatment, socioeconomic status, number of children, duration of previous lactation, type of contraceptive, and age of mothers and repeated measurements (before and after OC) showed that milk calcium was significantly affected by stage of lactation (p=0.0013). CONCLUSION: The use of hormonal contraceptive such as the combination pill (levonorgestrel 0.15 mg+ethynilestradiol 0.03 mg) and mini-pill (norethindone 0.35 mg) does not seem to affect the secretion of calcium and phosphorus in milk of mothers.

Adolescent↗

Prospective study of oral contraceptive use and risk of breast cancer in women.

In 1976, 118,273 female nurses 30-55 years of age with no history of cancer completed a questionnaire regarding possible risk factors. By 1986, after 1,137,415 person-years of follow-up, we had documented 1,799 newly diagnosed cases of breast cancer. Compared with the risk of breast cancer for nonusers of oral contraceptives, the multivariate relative risks were 1.07 (95% confidence interval, 0.97-1.19) for all users, 1.06 (95% confidence interval, 0.96-1.18) for past users, and 1.53 (95% confidence interval, 1.06-2.19) for current users--women who used oral contraceptives up to 2 years before diagnosis of breast cancer. We conclude that overall past use of oral contraceptives is not associated with a substantial increase in the risk of breast cancer. Although we did not find women who used oral contraceptives before the first pregnancy to have an increased risk of breast cancer, the number of women who used oral contraceptives for a long duration in early reproductive life was too small to permit firm conclusions regarding the risk in this subgroup.

Adult↗

In utero exposure to steroid contraceptives and outcome of pregnancy.

A cohort study of women who used steroid contraceptives during pregnancy was conducted in Chiang Mai, northern Thailand, between 1984 and 1987. There were 1,573 pregnancies in which the fetus was exposed to the injectable contraceptive Depo-Provera (The Upjohn Company, Kalamazoo, Michigan) (830 accidental pregnancies and 743 infants conceived before the mother started use of Depo-Provera), 601 accidental pregnancies in women who were using oral contraceptives, and 2,578 planned pregnancies with no steroid exposures (controls). Subjects were followed up for interview, and medical records were traced for birth weight. Women using Depo-Provera had more risk factors for adverse pregnancy outcomes than did the other groups. The adjusted odds ratios for low birth weight were increased for accidental pregnancies with fetal exposure to Depo-Provera (odds ratio (OR) = 1.5, 95% confidence interval (Cl) 1.2-1.9) or oral contraceptives (OR = 1.5, 95% Cl 1.2-2.0). The higher risk of low birth weight among infants exposed in utero to Depo-Provera or oral contraceptives is due in part to self-selection for adverse outcomes among women with unplanned pregnancies. However, among accidental pregnancies with Depo-Provera, the risk of low birth weight was significantly increased when conception was estimated to have occurred within 4 weeks of injection. The odds ratios were 1.9 (95% Cl 1.4-3.2) for injection-to-conception intervals of less than or equal to 4 weeks, 1.5 (95% Cl 0.9-2.3) for intervals of 5-8 weeks, and 1.2 (95% Cl 0.7-1.9) for intervals of greater than or equal to 9 weeks. This trend was highly significant. Thus, the authors conclude that early, high-dose in utero exposures to Depo-Provera may affect fetal growth.

Adult↗

Fatal stroke and use of oral contraceptives: findings from a case-control study.

A case-control study of women less than 40 years of age in England and Wales was performed to evaluate the risk of fatal stroke associated with the use of the newer, low-dose oral contraceptives. Included were 296 cases with subarachnoid hemorrhage, 105 cases with other hemorrhagic stroke, and 21 cases with occlusive stroke, all of which occurred during 1986-1988. Two living controls per case, matched for age and marital status, were chosen from the general practice lists. The power of the study was such that the minimum significant increased relative risk of subarachnoid hemorrhage associated with ever having used oral contraceptives that could have been detected with 90% certainty was 1.6; the equivalent value for occlusive stroke was 28.4. Relative risk was estimated by conditional logistic regression allowing for matching. The adjusted relative risk of subarachnoid hemorrhage associated with oral contraceptives was estimated to be 1.1 (95% confidence interval (CI) 0.6-1.9) for current use and 1.3 (95% CI 0.9-1.8) for ever use, while the equivalent relative risk of an occlusive stroke associated with ever use was 4.4 (95% CI 0.8-24.4). Oral contraceptive use may be associated with a small increase in the risk of subarachnoid hemorrhage. These data are consistent with a substantial increase in the risk of occlusive stroke associated with oral contraceptive use.

Adolescent↗

Does contraception modify the risk of endometriosis?

Long episodes of regular, prolonged, abundant menstrual flows are generally agreed to increase the risk of endometriosis. Since oral oestrogen-progestogen combinations reduce and intra-uterine contraceptive devices increase menstrual flow, an effect on the risk of development of endometriosis in women utilizing these forms of contraception could be expected. Analysis of the most recent epidemiological observations shows no consensus on a possible relationship between use of cyclic oral contraceptives and endometriosis, with an increase, a decrease, and no effect on the risk of developing the disease all being reported. A lower relative risk of endometriosis in previous users of the intrauterine contraceptive device was only found in two series, most of the other data suggesting a rise in risk or no effect. Further studies on the relationship between type of contraception and endometriosis are needed to demonstrate whether the risk of development of the disease could be influenced, and whether well tolerated, relatively inexpensive, long-term treatment might be available for symptomatic patients not desiring offspring.

Contraceptives, Oral↗

Contraceptive practice in women with systemic lupus erythematosus.

Since there are few data on the use of various birth control methods in systemic lupus erythematosus (SLE), we performed a cross-sectional study of the actual contraceptive practices in a group of 85 Finnish female SLE patients of reproductive age. We also recorded side-effects experienced during the use of oral contraceptives (OCs) and intrauterine devices (IUDs). The use of contraception was lower in SLE patients than in healthy women of the same age (59 vs 77%, P < 0.001). Sexually active SLE patients requiring contraception used more often barrier and natural methods (P < 0.001) and less often OCs (P < 0.05) than the corresponding healthy women. The risk of deep venous thrombosis in SLE patients while using oestrogen-containing OCs was slightly increased (RR 2.3, 95% CI 0.5 to 10.3). Twenty-five (78%) of the 32 patients, who had used progestagen-only contraceptives discontinued them because of side effects, which were mainly gynaecological. Major bleeding or pelvic infection did not occur during the use of IUDs.

Adolescent↗

Carbon monoxide production and reticulocyte count in normal women. Effect of contraceptive drugs and smoking.

Endogenous production of carbon monoxide (VCO), serum bilirubin (SB) and reticulocyte (retic) count have been followed during the menstrual cycle in 12 women (4 of them smokers) without contraceptive drugs and in 10 women (5 of them smokers) on contraceptive drugs. During the progesterone phase (Pph), VCO in the non-smokers was 18.2 +/- 2.1 mumol/mmol total body heme (TBH) and day (mean +/- 1 S.E.M.), compared with 10.1 +/- 1.0 during the estrogen phase (Eph). In the smokers, VCO was 10.4 +/- 1.9 during Pph and 12.5 +/- 0.7 during Eph. SB for the non-smokers was 5.2+/- 1.0 mug/ml during Pph and 3.9 +/- 0.5 during Eph, compared with 3.2 +/- 0.8 and 3.9 +/- 1.2, respectively, for smokers. The retic count for the non-smokers was 64.1 +/- 4.7 times 10(3)/mul during Pph and 17.7 +/- 5.1 during Eph. In the smokers the corresponding counts were 93.6 +/- 15.9 and 60.8 +/- 7.6. These results confirm earlier reports that VCO is increased during Pph and indicate that the rise could be due to a change in red cell catabolism, since it is concomitant with a significant increase in retic counts, which has not been found in earlier works on VCO, but which is known from reticulocyte studies. Furthermore, the results may indicate that persistent smoking affects the metabolism of CO and/or heme, since the smokers did not react with any change in VCO during Pph. In subjects using contraceptive drugs, VCO was significantly higher (14.9 +/- 0.6 on combined estrogen-gestagen drugs and 14.5 +/- 1.1 on continuous gestagens, respectively) than during Eph in non-smokers (10.1 +/- 1.0 mumol/mmol TBH and day), which might be taken as the baseline group. This indicates that the increased VCO in subjects on contraceptive drugs may be related to the activity of gestagens, which were concluded in all contraceptive drugs tested.

Adult↗

Use of combined oral contraceptive preparations alters the insulin sensitivity of fatty acid and ketone metabolism.

Eight women taking low-dose-oestrogen combined oral contraceptive preparations were compared to eight women in the luteal phase of the menstrual cycle during hourly incremental insulin infusions of 0 (basal), 0.005, 0.01 and 0.05 U/kg/h short-acting insulin. Dose-response relationships between insulin and intermediary metabolites were sought by analysis of variance applied to regression. For insulin (log) and glucose the slope of the relationship was significantly shallower in the oral contraceptive group. For insulin (log) and non-esterified fatty acids the slopes of the regression lines were not different between groups but lines were significantly displaced. For insulin (log) and total ketone bodies (log) slopes of the regression lines were not different but significant displacement was observed. At identical insulin concentrations women taking an oral contraceptive had higher non-esterified fatty acids (NEFA) (difference between groups +0.15 mmol/l, P less than 0.001) and total ketone bodies (log: -0.26 mmol/l, P less than 0.001). The potency of insulin action in oral contraceptive users versus the luteal group was 0.47 (P less than 0.01) for NEFA and 0.38 (P less than 0.001) for total ketone bodies. The results demonstrate, for the first time, in-vivo insulin resistance of NEFA and ketone bodies' metabolism induced by oral contraceptive use.

Adult↗

Is oral contraceptive use still associated with an increased risk of fatal myocardial infarction? Report of a case-control study.

OBJECTIVE: To investigate the association between fatal myocardial infarction and use of modern low-dose oral contraceptives. DESIGN: A case-control study. SETTING: General practices throughout England and Wales. SUBJECTS: 161 women aged under 40 dying from myocardial infarction during 1986-1988. Living controls (2 per case), matched for age and marital status, were chosen from general practice lists. Information was collected during structured interviews with general practitioners, and from postal questionnaires sent to surviving partners of the cases and to control women. MAIN OUTCOME MEASURES: Mortality from myocardial infarction in relation to many risk factors, notably oral contraception, as measured by relative risk. RESULTS: After allowing for the confounding effects of medical risk factors and for surgical sterilization, the overall relative risk associated with both current and past use of oral contraceptives was estimated to be 1.9 (95% CI 0.7 to 4.9, and 1.0 to 3.5 respectively). The relative risk associated with current use of preparations containing 50 micrograms of oestrogen, however, was estimated to be 4.2 (0.5 to 39.2). At least some of the relative risk associated with oral contraceptive use is likely to be attributable to the confounding effect of cigarette smoking, but it is impossible to estimate how much from the available data. CONCLUSIONS: If there was an increased risk of fatal myocardial infarction associated with oral contraceptive use in 1986-1988 it is likely to have been less than two-fold; in this study risks were slightly, but not significantly, elevated with both current and previous use. It may be that any increase in risk is associated solely with the older combined preparations containing 50 micrograms of oestrogen.

Adult↗

Contraceptive use among female adolescents.

Teenage pregnancy continues to be a problem in the United States despite the availability of reliable contraceptive methods. A pilot study was conducted to determine the use of reliable contraception by teenagers following an abortion or negative pregnancy test. The results indicated that 96.6% of the teenagers experiencing a therapeutic abortion and 49.6% of the teens having a negative pregnancy test reported choosing reliable contraception after the procedure or the test. At a subsequent clinic visit, however, only 27.5% in the abortion group and 5.7% in the negative pregnancy test group reported use of reliable contraception. Further research is needed to identify factors involved in teenagers' use or nonuse of contraception.

Abortion, Legal↗

The significance of oral contraceptives in causing chromosome anomalies in spontaneous abortions.

The significance of oral contraceptives in causing chromosome aberrations in the fetus was studied in 246 non-selected spontaneous abortuses using Q-banding technique. No significant difference in the frequency of abnormal karyotypes or in the sex ratio was found between 124 abortuses of women who had taken oral contraceptives in comparison with 122 abortuses of women who had never used oral contraceptives. The study did, however, show that women who had used oral contraceptives were significantly younger than women who had not used these pills. In addition, the gestational age of the chromosomally abnormal abortuses was on the average 6 days longer in the group of women who had used oral contraceptives than in the group who had not. The difference was significant only with regard to the karyotype 45,X.

Abortion, Spontaneous↗

The influence of a combined oral contraceptive on uterine activity and reactivity to agonists in primary dysmenorrhea.

The mechanisms underlying the therapeutic effect of an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol daily for 21 days) in primary dysmenorrhea were studied by recordings of uterine activity and reactivity to lysine (L) vasopressin (VP) and prostaglandin (PG) F2 alpha on the first day of menstruation in 14 women before and after one period of oral contraceptive treatment. During the first session, when all women had moderate to severe dysmenorrhea, intra-uterine pressure recording showed an intensive uterine activity, and bolus injections of LVP (6 pmol/kg body weight; 6 subjects) or PGF2 alpha (6 or 12 nmol/kg body weight; 4 subjects in each group) increased contractile activity and discomfort. After oral contraceptive treatment, spontaneous uterine activity, measured as total pressure area, decreased significantly (p = 0.02 and p = 0.03 in the VP and PG groups, respectively). The mean uterine responses to LVP and PGF2 alpha were on average smaller after oral contraceptive treatment and the women experienced minimal discomfort after this injection. It is suggested that inhibition of uterine activity could be an important mechanism for the therapeutic effect of gestagen-dominated oral contraceptives in primary dysmenorrhea and that reduced uterine reactivity to agonists might contribute to this effect.

Adolescent↗

Labeling emergency contraception.

According to the signers of a November 28 citizens' petition filed with the Food and Drug Administration (FDA), unintended pregnancies and abortions could be reduced significantly if the FDA would require the relabeling of several oral contraceptives as emergency or postcoital contraception, also known as "morning after pills." It has long been established that within 72 hours after unprotected intercourse or contraceptive failure, a specified combination of pills taken at specified intervals can reduce the risk of pregnancy by an estimated 75%. Although physicians at university health clinics, in hospital emergency rooms treating rape victims, and at some family planning clinics prescribe emergency contraceptives, other physicians are reluctant to do so without relabeling, and most women taking the pill do not know the correct dosage. Calling this a "critical public health issue," attorneys at the Center for Reproductive Law and Policy petitioned the FDA for a labeling change on the grounds that manufacturers are in fact "misbranding" pills by suppressing emergency contraceptive information. If pill makers rewrite their patient packet inserts, women undoubtedly would have far greater control over the occurrence of an unintended pregnancy, the attorneys said.

Americas↗

Male contraceptives under trial.

The International Planned Parenthood Federation held its 4th biological workshop in New Delhi on October 17-19, 1974. The topic of this meeting was "Agents affecting fertility in the male." 10 internationally known experts in the field of male reproductive physiology attended and each presented an up-to-the-minute account of their work in the field, followed by a full discussion. Much basic work was described, and the results of the latest human trials of male contraceptives were reported. Dr. F. Neumann of the Schering Company, Berlin, reported on clinical trials of the drug cyproterone acetate. This drug has been in the news for some time as a possible male contraceptive. It is found that small doses prevent sperm from maturing in the epididymis. This drug is already on the British market as Androcur. In large doses it is useful for curbing libido, and in this format it is used to control "sexual offenders." In the small doses at which it is useful as a contraceptive, the effects on libido are negligible, and the drug is at present undergoing human trials as a contraceptive agent. However, much work has still be done on, for example, long-term side effects. Another approach described by Dr. J. Frick from Innsbruck, Austria, is that of giving men a progestagen combined with testosterone. Whereas the progestagen has the effect of inhibiting sperm production in the testis, the testosterone compensates for androgen loss and maintains libido and male characteristics. Dr. Frick reported studies using 15 progestagen combinations, including a new drug provisionally titled R2323. The overall conclusion of the meeting was that there are still many problems to be solved, and it will be some years before a male contraceptive will be commercially available.

Contraception↗

Discontinuation of contraceptive use in Ghana.

Using data from the Ghana Demographic and Health Survey 1998, this paper analyzed the duration of use of a contraceptive method and the reasons for its non-use given by former users of contraception. The results showed that the duration of use tended to be short, particularly so for the use of condom and withdrawal. Injectable contraceptives and periodic abstinence tended to be used for relatively long periods. After type of method, a woman's age and residence (urban or rural) were the most significant predictors of duration of use. The reasons for not currently using contraception given by significant numbers of former users of pill and injectable contraceptives should concern service providers and educators.

Adolescent↗

Long term use of inert intrauterine contraceptive devices in 94 women in Israel.

A 22 year retrospective survey was undertaken in an Israeli family practice to determine how long inert (plastic only, unmedicated) intrauterine contraceptive devices could be safely left in place. Ninety four women were identified who had used 100 inert intrauterine contraceptive devices continuously for between five and 19 years. Fifty nine women complained of pain, increased uterine bleeding or increased vaginal discharge, but these were the reasons for removal of the device in only 32 women. There was only one case of pelvic inflammatory disease but this was treated without removal of the intrauterine contraceptive device. Of 14 women who requested to have their device removed after between five and nine years without having had any side effects, 11 women conceived within nine months. The results of the study indicate that inert intrauterine contraceptive devices can be safely left in place until the menopause. As it will take many years before the new type of copper devices can be shown to be as safe for long term use, it seems an appropriate time to reintroduce inert intrauterine contraceptive devices for women.

Adolescent↗

Determinants of contraceptive choice among single women in the United States.

Data from the 1983 National Survey of Unmarried Women are used to analyze characteristics that affect contraceptive decision-making among single women aged 20-29 who are exposed to the risk of pregnancy. Factors found to affect whether these women use a relatively effective method such as the pill or the IUD, use coitus-dependent methods or use no method include family structure at age 15, educational level, work status, religious affiliation, fertility relative to desired fertility, and past contraceptive failure. Bivariate analyses revealed notable differences between whites and blacks in contraceptive behavior. Multivariate analyses showed that while the decision to use a contraceptive method was somewhat affected by race, method choice was not. Overall, contraceptive decision-making was relatively unaffected by race, length of the relationship and current living arrangement.

Adult↗