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Potencies of oral contraceptives.

Oral contraceptives are combinations of estrogens and progestogens or, in the case of the mini-pills, progestogens alone. With specific test procedures in laboratory animals or human subjects, it is possible to assign potency evaluations to the components relative to the progestational, estrogenic, or antiestrogenic activities of the progestogen or to the estrogenic potencies of the estrogenic component. It might even be possible to quantify the synergistic effects of the estrogen on the progestational agent. Unfortunately, however, it is impossible now to amalgamate such assay results into single estimates of the potencies of the combinations (either the combination products per se or the combination tablets of sequential products). For example, an over-all estrogenic potency of a combination preparation would involve the integration of contributions form the estrogen itself plus the estrogenic products of metabolism of the progestogen minus the antagonistic effect of the progestational agent, if any. These factors cannot now be quantified independently, much less merged into a single figure of clinical significance. Further, even if it were possible to produce such an estimate, it is unlikely that the evaluation would be meaningful in relation to any putative side effect or adverse reaction, i.e., the alleged thrombogenic effects of oral contraceptives cannot currently be related directly to any measure of potency that will allow prediction of these clinical conditions from laboratory models. Any evaluation of the potential of a given contraceptive to produce a specific side effect will depend upon data generated with specific regard to that adverse reaction and the individual product in question.

Contraceptives, Oral↗

[Serum level of thyroxin-binding globulin under oral contraception (author's transl)].

The use of oral contraceptives results in an increase in thyroid-binding-capacity in conformity with a change of results by T3/T4-tests. Using Laurell-electrophoresis and an anti-serum produced by Behringwerke the determination of the thyroid-binding-globulin (TBG) in serum is easy to handle. TBG was determined in serum from 137 women using oral contraceptives for more than 3 months. The apllication of oral contraceptives is followed by a statistically significant increase in the TBG level in serum. Thereby oral contraceptives change the TBG-level in a different degree. Preparations with a marked estrogen potency on the average effect a higher TBG-concentration than those with progesterone activity derived by menses-delay test. The difference of TBG-level is statistically significant. According by the increase of TBG-concentration in serum is caused by estrogen, the extent of the increase is modified by the progesterone component.

Adolescent↗

Carbohydrate studies in women using a norethindrone triphasic oral contraceptive for eighteen months.

Twenty women were tested before and after eighteen months of use of triphasic oral contraceptive (TOC) containing norethindrone and ethinyl estradiol (7-7-7). The evaluation was with an oral glucose tolerance test and plasma glucose and insulin levels were measured. The results showed a lower fasting glucose and elevated one-hour insulin values after TOC use. These results suggest improved safety with these contraceptives.

Contraceptives, Oral↗

Phasic contraceptive pills and functional ovarian cysts.

This seven-case anecdotal report is presented to alert physicians to the possibility of the formation of functional ovarian cysts during use of phasic contraceptive pills. The patients were studied by the combination of history, physical examination, ultrasound examination, and in two cases surgery. The occurrence of functional ovarian cysts during the use of phasic contraceptive pills is well established while not well appreciated by practicing physicians. This seven-case presentation strongly suggests that phasic contraceptive pills may be a threat to patient health and safety. It is suggested that further studies be undertaken to better understand the pathophysiology.

Adult↗

Use of levonorgestrel implants versus oral contraceptives in adolescence: a case-control study.

OBJECTIVE: We compared continuation rates, effectiveness, satisfaction with method, side effects, and condom practices among adolescents using levonorgestrel implants (Norplant, Wyeth-Ayerst Laboratories, Philadelphia) as compared with oral contraceptives. STUDY DESIGN: We conducted a case-control study comparing 94 adolescents < or = 18 years old who received Norplant between March 1, 1992, and Nov. 1, 1993 (cases), with 94 age-matched controls who selected oral contraceptives during this same time period. By use of a structured questionnaire, information was obtained on pregnancy status, duration of use, patient satisfaction, side effects, and condom practices 6 months after initiation. Objective measures included weight on Norplant and oral contraceptive users and hematocrit on implant patients. RESULTS: Forty (43%) oral contraceptive patients compared with no Norplant patients discontinued their selected method before the 6-month interview (p = 0.00). Six patients prescribed oral contraceptives became pregnant. Ninety-three percent of Norplant users expressed overall satisfaction despite experiencing menstrual irregularity and cramping, amenorrhea, nervousness, abnormal hair growth or loss, rashes, and an increase in appetite more often than oral contraceptive users. Although Norplant patients also reported an increase in the duration of menstrual flow and number of days of spotting more often than oral contraceptive users, evaluation of hematocrits in these patients demonstrated a significant increase over the 6-month period (p = 0.00). Assessment of condom practices since initiation demonstrated that Norplant patients used condoms less often than oral contraceptive users (p = 0.00). CONCLUSION: Use of levonorgestrel implants may cause more side effects than oral contraceptives in the early months after initiation but provide superior protection against unintended pregnancy. We concluded that Norplant is a reasonable alternative for adolescents, especially when compliance is an issue.

Adolescent↗

A comparative study of Norinyl 1/35 versus Lo-Ovral in Ile-Ife Nigeria.

A comparative analysis of those women on Norinyl 1/35 versus those on Lo-Ovral showed those on Norinyl 1/35 were significantly (P less than or equal to 0.05) older than women in the Lo-Ovral group. There were no significant differences (P greater than or equal to 0.05) between the groups for other characteristics at admission. There were no significant differences (P greater than or equal to 0.05) between the groups at follow-up in the number of women reporting serious complications, menstrual complaints or other pill-related problems. The continuation rates at 12 months were 79.4 for the Norinyl 1/35 group and 76.7 for the Lo-Ovral groups. There were no pregnancies reported during the study period.

Adult↗

The use of triphasic oral contraceptives in a continuous use regimen.

OBJECTIVE: The objective of this study was to describe the characteristics of and outcomes and side effects in patients using triphasic oral contraceptives (OCs) in a continuous use regimen. METHODS: A retrospective review of patient charts from four community-based physician practices was conducted. All patients had been using triphasic OCs in a continuous regimen (i.e., to prevent withdrawal bleeding) for a planned duration of at least three 28-day cycles. Data collected through retrospective chart abstraction included demographic and clinical indicators, duration of and reason for continuous triphasic OC use, prior OC history and side effect incidence and treatment. RESULTS: Forty-three patients meeting the inclusion criteria had data of sufficient quality to be included in all analyses. These patients represented 603 total cycles. Nearly half of the patients (49%) indicated that their primary reason for continuous OC use was personal preference rather than medical reasons. More than half of the patients (56%) had previously used triphasic OCs in a noncontinuous regimen; 24% had no prior OC experience. The median duration of continuous use was 237 days (including right-censored patients; range, 55-994). Of the 39% of patients who terminated continuous use, the most common reason given was the desire to become pregnant (35%). Sixty-one percent of the patients reported no side effects from continuous use. The most common side effect occurring beyond Day 21 of continuous use was breakthrough bleeding (reported in four patients). Survival analysis indicated that time on continuous triphasic use was positively related to parity >0 (p<.05) and the absence of side effects (p<.1). CONCLUSION: The data suggest that successful continuous use is feasible with triphasic OCs, with few adverse side effects.

Adolescent↗

Patient acceptability and satisfaction with Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension).

The results from a User Satisfaction Questionnaire, Treatment Assessment Questionnaire, and Global Well-Being Schedule questionnaire administered to women participating in an open-labeled, nonrandomized, parallel, controlled study comparing a new monthly injectable contraceptive containing 25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate (E2C) (MPA/E2C) (Lunelle Monthly Contraceptive Injection) and a triphasic norethindrone (0.5, 0.75, 1.0 mg)/0.035 mg ethinyl estradiol (NET/EE) oral contraceptive (Ortho-Novum 7/7/7) are reviewed. Approximately 85% of all 1103 women enrolled in the comparative trial completed their initial and final questionnaires. To better assess the comparison of a new and extant method of contraception, outcome data were divided among MPA/E2C users and new and previous oral contraceptive (OC) users. Despite the inherent inequalities in comparing an injectable to an oral method of contraception, few treatment assessment and satisfaction outcomes were significantly different when comparing MPA/E2C users to new OC (NET/EE) users. More women in the MPA/E2C study group reported discomfort with their method than women in either NET/EE study group; however, only 19.4% of MPA/E2C users rated the administration of their contraceptive to be moderately uncomfortable or worse, compared to 11.7% of new NET/EE users and 13.4% of previous OC users. Among MPA/E2C users, 86.3% reported no interference with social activities compared with 90.4% of new NET/EE users. MPA/E2C and new NET/EE users were also similar in their responses recommending their respective contraceptive method to friends, with > 90% of both groups stating that they had a very favorable experience and would definitely recommend their method to a friend. In general, MPA/E2C was well accepted by women in the study group. Their attitudes and perceptions are similar to those of women who were starting OCs for the first time. These data support the premise that MPA/E2C may become a well accepted, first-line contraceptive option for women in the US.

Adolescent↗

Comparison of the effects of triphasic oral contraceptives with desogestrel or levonorgestrel on apolipoprotein A-I-containing high-density lipoprotein particles.

Recent observations suggest that the risk of coronary artery disease (CAD) is associated with both the level and composition of the two major populations of apolipoprotein (apo)-defined high-density lipoprotein (HDL) particles: those containing both apo A-I and apo A-II [Lp(AI,AII)] and those containing apo A-I without apo A-II [Lp(AI)]. While sex hormones are known to affect HDL, their influence on these apo-defined HDL particles is not known. We have determined the effects of two triphasic oral contraceptive (OC) formulations on these HDL particles in healthy normolipidemic women aged 21 to 35 years. The formulations contain comparable quantities of ethinyl estradiol (EE) and either desogestrel (DG), a minimally androgenic progestin, or levonorgestrel (LN), a more androgenic progestin. Lipid and lipoprotein levels were measured during the third week of the normal menstrual cycle and the sixth month of OC use. The DG/EE formulation significantly increased total cholesterol (C) 15%, triglyceride (TG) 99%, phospholipid (PL) 17%, apo A-I 28%, apo A-II 34%, apo B 21%, very-low-density lipoprotein cholesterol (VLDL-C) 238%, HDL-C 20%, and HDL3-C 28% (P < .02 to .005, n = 11), but not low-density lipoprotein cholesterol (LDL-C). The LN/EE formulation also increased total C 15%, TG 33%, apo A-I 15%, HDL3-C 21% (P < .05, n = 10), apo B 30% (P < .005), and, additionally, LDL-C 19% (P < .05). Both formulations increased Lp(AI,AII) (DG/EE, 34%, P < .005; LN/EE, 24%, P < .01). These changes reflected comparable increases of small (7.0 to 8.2 nm) and medium (8.2 to 9.2 nm) particles in the LN/EE group and a predominant increase of medium-sized particles in the DG/EE group. Also, in the LN/EE group but not the DG/EE group, there were fewer large (9.2 to 11.2 nm) particles. Lp(AI) increased only in the DG/EE group (25%, P = .075) and was due to the presence of more large particles. The level of Lp(AI) did not change in the LN/EE group, but the lipid/A-I ratio of these particles was lower (P = .012) and there were more small particles. Thus, triphasic OC formulations with progestins of different androgenicity had different effects on VLDL, LDL, and the level and composition of HDL particles with and without apo A-II, possibly reflecting estrogen/progestin/androgen balance. Estrogen dominance increases both Lp(AI,AII) and Lp(AI) and favors large Lp(AI) particles, while progestin/androgen dominance increases only Lp(AI,AII) and favors small particles. Because of the importance of HDL in the arterial wall physiology, OC formulations with different estrogen and progestin content may affect arterial wall health to a different extent.

Adult↗

Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol.

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.

Adult↗

The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. II. Serum lipid levels.

The response of lipids in the blood between two groups of six young women was compared. Group 1 took oral contraceptives and group 2 had never taken oral contraceptives. Two experimental diets supplied about 13% of the calories from protein, 36% from fat, and 51% from carbohydrate. Of the carbohydrate, 84% was either sucrose or wheat starch. Each diet was fed for 4 weeks in a cross-over design. In the portion of the research presented here, subjects were fed a high sucrose meal before each dietary period and after weeks 1 and 3 of each dietary period. Blood lipids were measured before and 30, 60, 120, and 180 min after each meal. Cholesterol and lipoproteins were not affected by the sucrose meal, but free fatty acid levels decreased significantly in both groups. The serum levels of triglycerides, beta-lipoproteins, and cholesterol were significantly higher in users than in nonusers of oral contraceptives. Free fatty acid levels were affected by an interaction between diet and time, and the decrease in response was greater after the sucrose than after the wheat starch diet. Triglycerides, cholesterol, and total lipids were not significantly different after the two carbohydrate diets.

Adult↗

Oral contraceptives.

Variations in the side chains attached to the gonadal hormones can produce marked changes in the potency of these compounds and can even change their predominant actions. Modification of testosterone renders it less androgenic and greatly enhances its progestational effect. The antifertility action of oral contraceptives may be exerted through any of several mechanisms: supression of follicular development, suppression of ovum expulsion or changes in endometrium or cervical mucus.

Anemia↗

[The action of Sequostat in comparison to Sequence Ovosiston on selected metabolic parameters].

The effects of two sequential oral contraceptive preparations, Sequostat (6 days ethinylestradiol 0.05 mg, 15 days ethinylestradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequence-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg) on triglycerides, total cholesterol, HDL- and LDL-Cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase and antithrombin III were studied in two groups of 46 and 29 young women respectively. Investigations were performed prior to the hormonal intake and after treatment for 3, 6 and 12 months. In nearly all parameters studied significant but minimal changes could be demonstrated which in most cases showed a minor degree in the Sequostat-group, while Sequence-Ovosiston exerted a less effect on glucose tolerance. A significant increase of HDL-cholesterol and a reduction of LDL/HDL-cholesterol relation could be demonstrated at least in the first six months, resulting from the estrogen dominance of the contraceptives.

Adolescent↗

Estrogen's role in endometrial cancer.

Data reported since 1975 indicate that the natural hormone estrogen may act as a carcinogen when unopposed by an adequate amount of progesterone. Carcinogenesis may proceed when it is present at a high level for a short time. It is generally accepted that 3 groups of women have been at risk of developing cancer from exogenous estrogen exposure: 1) women who took sequential oral contraceptives; 2) post-menopausal women who received estrogen replacement therapy; 3) girls with ovarian dysgenesis who received unopposed estrogen therapy at puberty. Similarly, 4 groups of women appear to be at risk of developing cancer form endogenous estrogen sources: 1) women with granulosa-cell or theca-cell ovarian tumors; 2) anovulatory women; 3) obese postmenopausal women; 4) women with liver disease. The falling incidence of endometrial cancer associated with diminished estrogen sales is the final proof of an association of estrogen exposure with development of disease.

Anovulation↗