Choosing contraceptive steroids and doses.
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Contraceptives, Oral↗
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Long-term effects of Depo-Provera on carbohydrate and lipid metabolism.
Long-term effects of injection Depo-Provera (depo-medroxyprogesterone acetate) on carbohydrate and lipid metabolism were studied in 157 women who were treated continuously for a mean duration of 43.3 months. The patients were matched with 162 controls for race, age, parity and height. Glucose tolerance was impaired with higher intolerance at longer duration. Glucose areas were significantly higher at 48 and 60 months of injection. Insulin levels were also significantly decreased at 30 minutes and increased at 150 minutes but the area was normal. Triglycerides were initially decreased, being significant at 36 months (p less than 0.001) and returned to normal at 60 months while cholesterols were significantly higher at 24 and 36 months (p less than 0.05) and 60 months (p less than 0.001). In view of these findings, Depo-Provera may have an advantage over oral pills on a short term basis as there are less alterations in carbohydrate and lipid metabolism.
Adult↗
Clinical experience with a triphasic oral contraceptive.
A triphasic combined oral contraceptive containing fluctuating amounts of ethinylestradiol and levonorgestrel was tested clinically in a multicenter trial at six hospitals in Norway. 367 women were included in the study, 3 588 cycles were studied, and the follow up period was 12 months. The one year continuation rate was 67%. Five pregnancies occurred during the study period. All of them had to be considered as patient failures. The causes for stopping medication were side effects in about 50% and the rest for personal reasons. The cycle control taking into account duration of bleeding, amount of flow, and intermenstrual bleeding was good and comparable to the low-dose monophasic combined pills. The incidence of side effects was low. One woman had an increase in systolic blood pressure to more than 140 mmHg. Thrombophlebitis was not registered. In conclusion the triphasic oral contraceptive was effective and had a good cycle control and low incidence of side effects.
Adult↗
Reproductive and hormonal factors and breast cancer in a Northern Italian population.
Between January 1980 and March 1983, data were collected to evaluate risk factors for breast cancer in a case-control study based on 368 women with breast cancer admitted to the General Hospital of Pordenone (a district in North Eastern Italy with a particularly high breast cancer mortality rate), and 373 age-matched controls. Nulliparity or low parity, late age at first birth and later menopause were associated with an increased risk of breast cancer. The elevated risk associated with nulliparity could be almost completely explained by marital status, thus pointing to a specific protection given by parity, rather than some putative influence of infertility or subfertility in breast cancer cases. Likewise, risk did not vary materially according to history of abortions when marital status was controlled for. Increased risk associated with later age at first birth, on the other hand, was not accounted for by marital status or parity. The population studied, though frequently multiparous, showed late average at first birth: this might, at least partly, explain its high mortality rate from breast cancer. The risk estimate was higher if menarche occurred below age 15; however, there was no evidence of a trend for the relative risk to rise with lower age at menarche. The use of oral contraceptives or other female hormones (such as oestrogen replacement therapy) did not appear to be related to the risk of breast cancer. The role of the major menstrual and reproductive variables considered (age at menarche, parity, age at first birth) was apparently stronger in pre-menopausal women, thus suggesting an influence of these factors (and possibly, their hormonal correlates) on one of the latter stages of the process of carcinogenesis.
Abortion, Spontaneous↗
Clinical and metabolic study of a new pill containing 20 mcg ethinylestradiol plus 0.150 mg desogestrel.
The clinical and metabolic effects of a short-term treatment with a combination contraceptive pill containing 0.150 mg desogestrel and 20 mcg ethinylestradiol were evaluated in a group of 17 healthy women. In spite of the low estrogen content, the pill exerted a good cycle control and the incidence of irregular bleedings was low. The minor side effects commonly associated with oral contraceptive (OC) use rarely occurred, and an improvement of premenstrual symptoms was reported during pill intake. As for the different biochemical parameters tested, the formulation induced a significant increase of fibrinopeptide A (FPA) plasma levels. However, the resulting increase of peptide was lower than that induced by pills containing 30 mcg ethinylestradiol. No significant modifications of plasma total cholesterol (T-CH) and low-density lipoprotein cholesterol (LDL-CH) were observed, while triglycerides (TG), high-density lipoprotein cholesterol (HDL-CH) concentrations and the HDL-CH/LDL-CH ratio significantly increased. A significant increase of apolipoproteins AI (Apo AI) and apolipoproteins AII (Apo AII) concentrations was also observed. Moreover, the pill did not alter fasting insulin and glucose levels and their response to an oral glucose tolerance test (OGTT). It may be concluded that this new formulation can be considered acceptable for clinical use, mainly in consideration of the minor or no changes in the biochemical parameters regarded as risk factors for venous and arterial diseases.
Adult↗
A morphometric study of the effect of oral norethisterone or levonorgestrel on endometrial blood vessels.
A morphometric study was undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens.
Administration, Oral↗
Oral contraceptives containing chlormadinone acetate and cancer incidence at selected sites in the German Democratic Republic--a correlation analysis.
The use of oral contraceptives containing chlormadinone acetate in 1972 by women of 13 districts (out of 15) of the GDR has been related to the incidence of cancer of breast, corpus uteri, and ovary during the period 1961 to 1980. Cancer incidence was represented by cohort parameters showing the risk of the cohorts in relation to each other. No statistically significant association between the two events was noted. Although not significant, our data are consistent with an elevated relative risk for breast cancer of 1.3 and a decreased risk for ovarian cancer of 0.5.
Adult↗
Maternal exposure to exogenous sex hormones in relation to birth weight of offspring.
Birth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (less than 25, 25-29, and 30-39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for "threatened abortion," but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal growth.
Birth Weight↗
Developing applications of prostaglandins in obstetrics and gynecology.
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Abortion, Induced↗
Clinical chemistry in women treated with levonorgestrel implants (Norplant) or a TCu 200 IUD.
Two groups of implant users and two groups of IUD users participated in the study at different times. In the first groups, fractionation of lipoproteins was performed on serum samples from 28 subjects who had used the implants for 37 months and from 26 subjects who had used the Copper TCu 200 for 30 months. Users of the implants had significantly lower levels of total cholesterol, triglycerides and LDL-cholesterol than users of the IUDs. HDL-cholesterol levels were not different between the groups. In the other groups of women, general chemistries and selected hormone assays were carried out on samples from 30 subjects who had used implants for 51 months and from 24 subjects who had used the TCu 200 IUDs for 43 months. The parameters studied were the SM-12 chemistry group profile, estradiol, cortisol, testosterone, triiodothyronine, thyroxine and thyroid stimulating hormone. In the implant group, mean serum glucose levels were statistically significantly elevated and inorganic phosphorus levels were significantly reduced as compared to the IUD group. In both cases all individual measurements were within the normal range for the population. Testosterone and triiodothyronine levels in the implant group were significantly lower than in the IUD group, but no individual values were outside the normal range for the population. Mean values for all other parameters were not significantly different between the groups.
Adult↗
Oral contraceptives, lipids and cardiovascular disease.
Evidence for the involvement of changes in lipid metabolism and oral contraceptive use in the development of cardiovascular disease is briefly reviewed with particular reference to the main object of the article, to assess the effect of different oral contraceptive formulations on serum lipid levels. The preferred formulations should contain a low dose of ethynyloestradiol and should not increase serum levels of cholesterol and LDL-C or reduce those of HDL-C. Such formulations appear to be the triphasic one containing ethynyloestradiol and levonorgestrel and the ethynyloestradiol-desogestrel combination, which appears to be unique in that it may actually increase HDL-C. However other determinants in addition to effects on lipid metabolism will be important in deciding the choice of an oral contraceptive. Any changes which do occur in serum lipid concentrations with OC use appear within the first three months and do not appear to be progressive with continued use after this time.
Adult↗
Vaginal administration of a combined oral contraceptive containing norethisterone acetate.
The effects of vaginal administration of an oral contraceptive pill containing 1 mg of norethisterone acetate and 0.05 mg of ethinyl oestradiol were studied in 20 subjects for a total of 57 cycles. The results show effective ovulation suppression in the two dose regimens used. The lower dose regimen was associated with fewer side effects and no breakthrough bleeding. No significant change was observed in the serum concentration of glucose, total proteins, albumin, cholesterol and HDL after several cycles of treatment in both dose regimens used. It is concluded that vaginal administration of this preparation of oral contraceptives is an effective alternative method of hormonal contraception.
Adult↗
The association between vaginal bleeding patterns and reasons for discontinuation of contraceptive use.
This paper describes the relationship between menstrual bleeding patterns recorded and reasons for discontinuing method use given by women using one of four types of hormonal contraception: combined oral pills, progestogen-only oral pills, a vaginal ring or depot-medroxyprogesterone acetate (DMPA). The women were recruited to five clinical trials, each of which lasted at least 48 weeks. The subject's reason for discontinuation was recorded if she stopped contraceptive use before the scheduled time. Overall, the reason expressed for discontinuing method use was a close reflection of the subject's experience. Among women using either type of oral contraceptive or a vaginal ring, subjects who discontinued for a non-menstrual reason or were lost to follow-up had bleeding patterns which did not differ markedly from those of women who continued method use. Only in the DMPA group was there any evidence that women who complained of non-menstrual side effects or were lost to follow-up might have ceased method use because they were unwilling or unable to tolerate their bleeding patterns. Subjects who discontinued because of amenorrhea had few bleeding/spotting days and at least one prolonged bleeding-free interval; women who complained of longer bleeding had long episodes and short intervals. Women who reported heavier bleeding had patterns which were similar to, but less extreme, than those of subjects who reported longer bleeding. The complaint of irregular bleeding, however, did not concur with the bleeding patterns recorded, regardless of contraceptive method. The predominant menstrual disturbance in this group of women was frequency of bleeding. They had no special difficulty in predicting either the time of onset or the length of their bleeding episodes. There were marked differences between individuals in terms of their acceptance of bleeding disturbances. Nevertheless, the results of this study confirm the importance of counselling. Women using DMPA tolerated far greater menstrual disruption than subjects using any other method. Subjects using an oral contraceptive were unlikely to have been warned of potential bleeding problems; when they encountered any, they tended to cease method use. In contrast, subjects using DMPA would have been advised to expect irregular patterns and possibly amenorrhea; prepared for such disturbances, their perseverance was remarkable.
Administration, Intravaginal↗
Oral contraceptives and mortality from circulatory system diseases: an epidemiologic study in Taiwan.
An epidemiological study on the association between oral contraceptive (OC) use and circulatory system disease (CSD) mortality undertaken in Taiwan by proxy interview of closest family members of 306 deceased cases, 305 deceased controls, and 611 healthy neighborhood controls indicated that the relative risk between the cases and health controls was 0.98 (0.62-1.54) and that between cases and health controls was 0.82 (0.56-1.21). Use of OC by Taiwanese women has not produced any overwhelming adverse effects on CSD mortality.
Adult↗
The effect of an oral contraceptive containing ethinylestradiol and desogestrel on hair growth and hormonal parameters of hirsute women.
A group of 22 hirsute women was treated with a combination of 0.030 mg of ethinylestradiol and 0.150 mg of desogestrel (EE-DG) for 6 or 12 months. After 6 months the hair growth was decreased in 17 patients. There was a significant decrease in testosterone/sex hormone binding globulin (T/SHBG) ratio and serum dehydroepiandrosterone sulphate (DHEAS) levels. The changes in the hirsutism and the T/SHBG ratio showed correlation (rho 0.36, P less than 0.05). The patient groups with the best and the poorest clinical response differed in terms of summed changes in the T/SHBG ratio and DHEAS. These findings suggest that the therapeutic effect of the EE-DG is based on combined changes in the related hormone levels.
Adolescent↗
Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception. II. Effect of postovulatory administration on ovarian function and endometrium.
A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinylestradiol (EE) was administered orally at 36 hours after the detection of the luteinizing hormone peak and again at 48 hours in 12 healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17 alpha-hydroxyprogesterone, and estradiol (E2) in control (placebo) and treatment cycles. Five subjects showed no significant change in the levels of these steroids but had a shortened luteal phase. The treatment significantly decreased both P and E2 levels in three subjects, while two subjects showed diminished E2 levels only. The remaining two subjects had lower P levels and fluctuating E2 patterns. Endometrial biopsies from both study cycles indicated asynchronous development of the epithelial and stromal components in the treatment cycle. These findings (abnormal luteal phase steroid levels and duration and outphased endometrial development) indicate that corpus luteum function was variously affected by the action of norgestrel-EE treatment.
Adult↗
The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use.
Sixty-one women were randomly assigned to use one of two different triphasic oral contraceptives (OCs), for one year's time (Ortho Novum 777, Ortho Pharmaceutical Corp., Raritan, NJ, and Triphasil, Wyeth Laboratories, Philadelphia, PA), containing the progestins norethindrone and levonorgestrel, respectively. The carbohydrate metabolism was evaluated using the oral glucose tolerance test before OC use and at the end of the 12th month. Both plasma glucose and insulin levels were measured. The fasting glucose value in the norethindrone-containing OC group (777) was significantly lower at the 1-year testing. All other values were unchanged. These data demonstrate that the triphasic oral contraceptive preparations currently in use have minimal effects on carbohydrate metabolism.
Adult↗
Neoplasia of the cervix uteri and contraception: a possible adverse effect of the pill.
The incidence of biopsy-proven cervical neoplasia during a 10-year follow-up was determined in 6838 parous women who entered the Oxford-Family Planning Association contraceptive study while using oral contraceptives and 3154 parous women who entered the study while using an intrauterine device (IUD). Risk factors for cervical neoplasia, continuation of attendance at family planning clinics, and frequency of examination by cervical cytology were similar in the two groups. All 13 cases of invasive cancer occurred in women in the oral contraceptive group; 9 had more than 6 years' use of the pill. Both carcinoma-in-situ and dysplasia also occurred more frequently in the oral contraceptive group than in the IUD group, and when the two conditions were considered together there was a trend in incidence with duration of oral contraceptive use. The incidence for all three forms of neoplasia combined rose from 0.9 per 1000 woman-years in those with up to 2 years' pill use to 2.2 per 1000 woman-years in those with more than 8 years' pill use. Amongst IUD users, there was no such trend in incidence with duration of use: the rate fluctuated around 1.0 per 1000 woman-years. The great majority of cases of invasive cancer were detected by means of cervical smears and were treated while the disease was still curable. Long-term users of oral contraceptives should have regular cervical cytological examination.
Adult↗