What role for Qlaira in contraception?

Around 25% of women in the UK aged 16-49 years use oral contraception.1 Annually, around 5 million combined oral contraceptive (COC) items are prescribed in primary care in England alone, at a cost of over pound40 million. The effectiveness of such contraception depends on correct and consistent use of the pills and is influenced by unwanted effects that can lead to discontinuation (e.g. bleeding irregularities), and by adherence to specified procedures for when a pill is missed. Qlaira (Bayer plc) is the first licensed COC in the UK to include the oestrogen estradiol valerate (E2V, which is metabolised to oestradiol, a natural human hormone) and the progestogen dienogest (DNG). It has been marketed as "the first and only COC to deliver...the same oestrogen as produced by a woman's body". In theory, it might be less likely than other COCs to cause unwanted effects. However, it has a complex dosage regimen, and has its own missed-pill guidance which differs substantially from that for other pills.3 Here we review the effectiveness and place of Qlaira.

Efficacy and safety of a 28-day oral contraceptive with 7 days of low-dose estrogen in place of placebo.

BACKGROUND: The study was conducted to evaluate the efficacy and safety for the prevention of pregnancy of a 28-day oral contraceptive (OC) containing 150 mcg desogestrel (DSG)/20 mcg ethinyl estradiol (EE) for 21 days followed by 7 days of 10 mcg EE (Cette-28). STUDY DESIGN: A 6-month, prospective, multicenter, single-arm study was conducted in 1302 women aged 18-45 years. RESULTS: Over six cycles of treatment, the cumulative risk of pregnancy among all treated subjects (n=1262) was 0.9%. The Pearl Index for women 18-35 years of age (n=1042) was 2.20, including 9 pregnancies with estimated conception dates during active drug ingestion or up to 7 days after the last combination tablet. The rate of unscheduled bleeding was low and the duration of scheduled bleeding was approximately 2 days during each of the six treatment cycles. The safety profile was similar to what has been reported for other OCs. CONCLUSION: This low-dose, 28-day OC incorporating 7 days of 10 mcg EE during the hormone free interval is effective and safe for the prevention of pregnancy and is well-tolerated by women.

The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation.

Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12-0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09-0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08-0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01-0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38-0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42-0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.

On the epidemiology of oral contraceptives and disease.

PIP: Adverse and beneficial effects, especially with regard to mortality rates, of oral contraceptives (OC) are reviewed. In 1980 approximately 80 million women used OCs worldwide. OCs were first marketed in the United States in the 1960's, but by the 1980's low-dose combination pills with less estrogen and progesterone content became widespread along with the minipill, injectable preparations depo- medroxyprogesterone DMPA, and norethindrone containing capsules. Relative disease risk estimates are based on cohort studies and case- control studies. The Royal College of General Practitioners RCGP Oral Contraceptive Study of 1974 involved 46,000 women aged over 15 (50% were OC users, 50% were nonusers) the Oxford Family Planning Association Contraceptive Study of 1976 recruited 17,032 women aged 25-39, 56% of whom used OCs, and the Walnut Creek Contraceptive Drug Study of 1981 studied 16,638 women aged 18-54 of whom 28% were OC users and 33% were former users. A somewhat elevated mortality among ever-users of OCs in the order of 20% seems to be indicated by these studies mostly attributable to diseases of the circulatory system. Current OC use is also a risk factor in thrombotic stroke of the order of 4 or 5, but former use of OCs lowers the risk to 2. The effect of OC dose and formulation, duration of use, and predisposing factors on hemorrhagic and thrombotic stroke appears to be inconclusive with varying data from different studies. There is evidence for some increase in ischemic heart disease among current OC users, and also a 2-fold increase of myocardial infarction (MI) when smoking, serum cholesterol, and hypertension is taken into account, moreover higher estrogen dosage also contributes to a higher incidence of MI. There is also a 5-fold increase of venous thromboembolism among OC users induced by duration of use and estrogen potency, as OCs seem to promote atherogenesis, although the roles of progesterone and estrogen are conflicting. combination pills reduce the rate of endometrial cancer, provided protection against ovarian cancer, and do not seem to increase breast cancer incidence, although the relative risk of cervical cancer is elevated. Mortality risks with older OCs outweigh the benefits.^ieng

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.

The relationship between mood and sexuality in women using an oral contraceptive as a treatment for premenstrual symptoms.

This study investigated the effects of a triphasic oral contraceptive (OC) on mood and on sexual interest in a group of 45 women with premenstrual complaints. Subjects made daily ratings of mood and sexual interest for one baseline cycle and were then randomly assigned to receive either placebo or OC for 3 mo. Women who received the OC reported decreased sexual interest during the menstrual and postmenstrual phases of the cycle. The predominant effect of both the OC and the placebo on mood was one of improvement, particularly during the premenstrual phase. There was little evidence of co-variation of mood and sexual interest in either group. Although the mechanism for the adverse effects of the OC on levels of sexual interest in unknown, it is clear that this effect was not simply a consequence of pill-induced negative mood change. The findings provide evidence that mood and sexual desire are dissociable and suggest that OCs can have direct effects on women's sexuality.

PIP: In Montreal, Canada, after 45 women who were seeking treatment for self-reported moderate to severe premenstrual changes made daily ratings of mood and sexual interest for 1 baseline cycle, they were blindly allocated to a group receiving a triphasic oral contraceptive (OC) Synphasic for 3 months or a group receiving a placebo for 3 months. Researchers wanted to determine the effects of the OC on mood and on sexual interest. Ratings of depression and sexual interest in both groups demonstrated significant cyclicity. For example, depression scores were highest during the premenstrual phase and lowest during the postmenstrual phase. Sexual interest peaked in the postmenstrual phase and bottomed out in the premenstrual phase. Both groups experienced a loss of cyclicity for mood and sexual interest by the 3rd treatment cycle. During the premenstrual phase, depression scores fell significantly in both groups (p .01), but an increase in sexual interest did not occur. During the menstrual phase, the OC group experienced a considerable drop in sexual interest (p .01), but the mood did not change. On the other hand, postmenstrually, the mood worsened, not significantly however, among the OC users, coinciding with a significant reduction in sexual interest (p .01). Yet mood and sexual interest were not correlated. In fact, covariation of mood and sexual interest basically did not occur in either group. Generally, both the OC and the placebo improved the mood, especially during the premenstrual phase. The negative effect of the OC on sexual interest was not just a result of OC induced negative mood change. These results show that mood and sexual desire are not linked. They intimate that OCs directly influence women's sexuality.

Endometrial abnormalities occurring in young women on long-term sequential oral contraception.

Recently the occurrence of adenocarcinoma of the endometrium has been reported in young women exposed to sequential oral contraceptive agents for long periods of time. Twelve young women who had been using Oracon for periods of from 13 to 93 months were subjected to office endometrial aspirations. Tissue specimens showed endometrium which varied in diagnosis from proliferative endometrium to severe atypical adenomatous endometrial hyperplasia bordering on endometrial carcinoma in situ. Adenomatous endometrial hyperplasia is though by many investigators to be a precancerous condition. The progression of endometrial changes from benign proliferation to cystic hyperplasia and adenomatous hyperplasia accompanied by varying degrees of anaplasia in young women exposed to Oracon for long periods of time is significant. It is not surprising, therefore, that adenocarcinoma of the endometrium has been reported in these women at an age where this condition had been relatively uncommon prior to the use of sequential oral contraceptives.

Adenocarcinoma of the endometrium in women taking sequential oral contraceptives.

Abnormal bleeding while taking oral steroidal contraceptives has been managed by changes in pill or addition of estrogen or progestin moieties. Diagnostic procedures, classically indicated, are universally not undertaken or postponed. Three cases of adenocarcinoma of the endometrium in relatively young patients using sequential oral contraceptives for cause are presented to reiterate the need for tissue diagnosis when abnormal bleeding occurs as a common side-effect of contraceptive therapy.

Endometrial carcinoma in young women taking oral contraceptive agents.

The first 21 cases recorded in the Registry for Endometrial Carcinoma in Young Women Taking Oral Contraceptive Agents are reported. We have found no other such cases in the literature, and indeed several authors have stated that these agents, because of their predominantly progestional action, would be expected to be protective against this disease. In 8 of the 21 patients, factors were present which militated against a close relation between oral contraceptives and carcinoma, and 5 of these 8 patients had taken only or predominantly combined agents. On the other hand, 11 of the remaining 13 patients took sequential agents, a ratio directly opposite that of the usage of combined and sequential agents in the American population. The possible reasons for the excess of sequential agents, chiefly Oracon, are discussed, and directions for future study are suggested.

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.

Endometrial carcinoma and oral contraceptive agents.

Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens.

Clinical assessment of a new triphasic oral contraceptive.

One hundred twenty women completed 901 woman-months of birth control with a new triphasic oral contraceptive. No pregnancies occurred, and good cycle control was achieved. Spotting and breakthrough bleeding were minimal, and amenorrhea did not occur. Changes in body weight and blood pressure were not statistically significant. The triphasic compound was well tolerated. Headache and dizziness were frequent complaints during the initial cycles but tended to subside within a few months.

PIP: The efficacy and safety of a new triphasic oral contraceptive (OC) were evaluated in a trial involving 120 women ages 18-33 years for a total of 901 woman-months of observation. 1 monthly cycle of this triphasic OC provides 6 tablets of 30 mcg ethinyl estradiol (EE) and 50 mcg levonorgestrel (LNg), 5 tablets of 40 mcg EE and 75 mcg LNg, and 10 tablets of 30 mcg EE and 125 mcg NNg. No pregnancies were reported during treatment. Cycle duration was significantly shorter during than before treatment. Before treatment, 88.6% of subjects had cycles of 29-32 days; after treatment, 74.3% had cycles of 20-28 days. The duration of menstruation was 2-5 days in 96.9% of treatment cycles, and the amount of flow was light to moderate in 94.2%. Breakthrough bleeding occurred in 0.4% and spotting in 1.0% of cycles; there was no amenorrhea. Side effects most frequently reported were headache (13.3%) and dizziness (8.2%). Changes in body weight and blood pressure were minimal.

Evaluation and therapy of breakthrough bleeding in women using a triphasic oral contraceptive.

This study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB persisting after three cycles. The new users were compared with a control group of 696 women who had used various OCs for at least 6 months. The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the first 3 months, respectively. Breakthrough bleeding occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively. We hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB. Seventy women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months. Breakthrough bleeding was more likely (P less than 0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.

PIP: this study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1259 women who received a triphasic oral contraceptive (OCs; 7-7-7) for the 1st time and to evaluate a hypothesis of management for BTB persisting beyond 3 cycles. The new users were compared with a control group of 696 women who had used various OCs for at least 6 months. The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the 1st 3 months, respectively. BTB occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively. The authors hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB. 70 women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months. BTB was more likely (p0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.

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.

PIP: Carbohydrate metabolism was investigated over 1-year period in new users of 2 different triphasic oral contraceptives (OCs)--Ortho Novum 777, which contains the progestin norethindrone, and Triphasil, in which levonorgestrel is the progestin. The 2 groups of women were similar in terms of age, parity, and weight. Carbohydrate metabolism was assessed through use of the oral glucose tolerance test before the onset of OC use and again after 12 months of use. In terms of plasma glucose results, only 1 value changed significantly during the study period; fasting glucose was lower than baseline in women taking the norethindrone triphasic OC. There was no significant change among users of either triphasic during the study period in plasma insulin levels. It is now believed that the elevations in birth plasma glucose and insulin levels recorded in earlier studies of OC users reflected the effects of the high dose of synthetic steroids used in these formulations, especially the progestins. The OCs that have been used since the 1980s indicate that low amounts of estrogen also improve carbohydrate metabolism, presumably by inhibiting the degradation of insulin. There are some indications that norgestrel tends to have a greater adverse effect on carbohydrate metabolism than norethindrone, perhaps accounting for the lowered fasting glucose in users of the norethindrone triphasic OC in this study. With norethindrone, the estrogen effect on carbohydrate metabolism predominates, but no significant fasting glucose change seems to occur when levonorgestrel counters the estrogen's improving effects on carbohydrates. Overall, these findings provide reassurance that the triphasic OCs currently in use have minimal effects on carbohydrate metabolism in addition to providing good cycle control and high rates of protection against pregnancy.

Letter: Sequential oral contraceptives.

PIP: Lyon, Silverberg, and Makowski published papers showing that young women taking long-term sequential oral contraceptives, especially Oracon, may develop adenocarcinoma of the endometrium. Other reports have shown that sequentials may cause adenomatous hyperplasia accompanied by severe degrees of anaplasia. All patients studied were asymptomatic, and the majority were oligomenorrheic prior to using sequentials. Patients who choose to continue with these agents should be closely observed and subjected to office endometrial aspirations at 6-month intervals. If adenomatous hyperplasia is diagnosed, patients should be encouraged to use nonsteroid forms of contraception. Repeat aspiration should be performed in 3-6 months; the patients should keep basal body temperature records. If situation persists and the adenomatous hyperplasia persists for 3-6 months, oral or parenteral progesterone therapy is indicated. It is believed that progestins will reverse the adenomatous hyperplasia. If it does not revert to secretory endometrium and severe, atypical adenomatous hyperplasia is found, hysterectomy may be indicated.^ieng

Histology of the endometrium in long-term use of a sequential oral contraceptive.

Non-atypical adenomatous hyperplasia was found in 13.5% of 111 biopsies obtained from long-term, predominantly black, users of Oracon. An association between length of time of use (95 cycles for those with adenomatous hyperplasia versus 73 for those without) and the development of adenomatous hyperplasia was noted, but there was no association with hypertension or obesity. Cystic glandular dilatation was seen in 63% but was not thought to represent hyperplasia. No more advanced lesions were seen.

Oral contraceptives and neoplasia.

PIP: Some of the available data concerning the suspected association between oral contraceptive (OC) use and the development of cancer is surveyed, and the attempt is made to evaluate possible associations between OCs and human neoplasia in light of pregnancy risk or benefit of oral contraception. The principal investigative methods in humans include various epidemiologic approaches, and the methodologies most often used are case reports (tumor registries), disease rates and trends, case-control studies, and cohort studies. These methods cannot prove a causal relationship between exposure to a possible carcinogen and the occurrence of disease. Consistent positive or negative evidence, confirmed by multiple epidemiologic approaches, can be used to guide physicians and regulatory agencies in formulating policy for the clinical use of OCs. Both the progestogen-only and the combined OCs have been shown to have a protective effect on the development of benign breast disease with this protective effect not appearing until 2 years of use. Long-term combined OC use appears to be related to the development of benign liver neoplasia, and this risk increases with the dose of the steroid and the age of the user. These lesions are quite rare but may be life threatening because of potential spontaneous rupture and hemorrhage. Long-term postmenopausal use of estrogens appears to increase significantly the risk of developing endometrial hyperplasia and adenocarcinoma of the endometrium. Estrogens appear to be related to the growth of pre-existing uterine leiomyomas. Endocervical cells under the influence of progestogens may develop adenomatous changes, and these benign changes have on occasion been misinterpreted as carcinoma.^ieng

Multi-centre open study of a triphasic levonorgestrel-ethinyloestradiol combined oral contraceptive ('Trinordiol').

A long-term, multi-centre open study was carried out to evaluate the efficacy, cycle control and side-effects with a triphasic, combined oral contraceptive containing levonorgestrel and ethinyloestradiol ('Trinordiol'). A total of 2517 women completing at least 1 cycle of treatment was followed up at 2 to 3-monthly intervals; the overall number of cycles on treatment was 37,090. During treatment, only 2 pregnancies occurred which were attributable to pill failure. Cycle control was good: cycle irregularities were 9.6% overall, but were most common (19.6%) during the first 3 cycles. Only 3.8% of patients withdrew from the study for this reason. Side-effects were those commonly seen with oral contraceptives, and they produced a drop-out rate of only 13.9%. There were no clinically significant effects on blood pressure or body weight. The results also suggested that 'Trinordiol' has a beneficial effect on pre-existing acne.

Combined clinical, histological and stereomorphometric studies with a new oral contraceptive of normophasic type: Fysioquens.

PIP: Fysioquens, a new contraceptive based on the normophasic scheme (0.050 mg [EE] ethinyl estradiol for the first 7 days followed by 0.050 mg EE and 1 mg lynestrenol for 15 days) was administered to 120 patients for a total of 2281 cycles. No pregnancies and/or dropouts were recorded. Cycle control was very good and the incidence of irregular bleedings was low (1.6%). Endometrial biopsies taken on cycle day 9-11 (tablet day 5-7) from 50 Fysioquens patients treated for more than 2 years were compared blindly to 50 biopsies taken on cycle 9-14 from 50 controls (without hormonal therapy). Some anomalies were observed in both groups with similar incidence (Fysioquens 10/50; Control 7/50). A 2nd biopsy taken 6 months later on cycle day 24-26 (tablet day 20-22) in the 100 Fysioquens patients with some endometrial anomalies on tablet day 5-7 revealed that this abnormal picture had spontaneously disappeared without interruption of treatment. The stereomorphometric comparison between the 10 abnormal Fysioquens biopsies taken in the 1st part of the cycle and 6 normal biopsies showed a significant increase in glandular diameter and in % volume of glandular lumen. The stereomorphometric study of the 10 biopsies taken 6 treatment cycles later on cycle day 24-26 (tablet day 20-22) in comparison with 7 normal control biopsies revealed a very significant decrease in glandular diameter, glandular lumen, and glandular volume, resulting in a very significant increase in stroma. It is consequently concluded that the abnormal biopsies observed in the beginning of the cycle in some treated patients is due only to a transitory estrogenic effect and that the early administration of progestagen in the normophasic dosage scheme not only counteracts this effect but could play a protective role against hyperplasia.^ieng

Evaluation of a new triphasic oral contraceptive in private practice.

We evaluated the clinical and metabolic effects of a new triphasic regimen developed in the continuing attempt to reduce the dose of estrogen and progestogen in oral contraceptives. A combination of ethinyl estradiol (EE) and levonorgestrel (LNg) was used (six tablets with 30 micrograms EE + 50 micrograms LNg, five tablets with 40 micrograms EE + 75 micrograms LNg, and 10 tablets with 30 micrograms EE + 125 micrograms LNg), also known as Triphasil (Wyeth). In a private practice, 409 subjects participated in 7,286 treatment cycles. Three pregnancies occurred, all due to subject failure. Menstrual regulation was excellent and the incidence of side effects extremely low. Withdrawals from the study for possibly drug-related medical reasons totaled 9.0% through 56 cycles of treatment. Metabolic changes also were evaluated in 14 of these women over a 6-month period. The only statistically significant increase in carbohydrate values occurred at 6 months. The mean glucose level at 30 minutes of the oral glucose tolerance test was above the baseline mean value, but serum insulin levels showed no statistically significant deviation. Lipid values presented are total lipids, total cholesterol, triglycerides, alpha-, beta-, and pre-beta-lipoproteins, and high density and low density lipoprotein cholesterol. There was no statistically significant difference between the mean values at baseline and those during treatment for any lipid variable. These results indicate that this triphasic oral contraceptive has a high degree of efficacy, a low incidence of side effects, excellent cycle control, and high subject compliance, and would seem to indicate a minimal influence on the metabolism of lipids and carbohydrates in the small number of subjects studied.

PIP: We evaluated the clinical and metabolic effects of a new triphasic regimen developed in the continuing attempt to reduce the dose of estrogen and progestogen in oral contraceptives. A combination of ethinyl estradiol (EE) and levonorgestrel (LNg) was used (6 tablets with 30 microgram EE + 50 microgram LNg, 5 tablets with 40 microgram EE + 75 microgram LNg, and 10 tablets with 30 microgram EE + 125 microgram LNg), also known as Triphasil (Weyth). In a private practice, 409 subjects participated in 7,286 treatment cycles. 3 pregnancies occurred, all due to subject failure. Menstrual regulation was excellent and the incidence of side effects extremely low. Withdrawals from the study for possibly drug-related medical reasons totaled 9.0% through 56 cycles of treatment. Metabolic changes also were evaluated in 14 of these women over a 6-month period. The only statistically significant increase in carbohydrate values occurred at 6 months. The mean glucose level at 30 minutes of the oral glucose tolerance test was above the baseline value, but serum insulin levels showed on statistically significant deviation. Lipid values presented are total lipids, total cholesterol, triglycerides, alpha-,beta, and pre-beta-lipoproteins, and high density and low density lipoprotein cholesterol. There was no statistically significant difference between the mean values at baseline and those during treatment for any lipid variable. These results indicate that this triphasic oral contraceptive has a high degree of efficacy, a low incidence of side effects, excellent cycle control, and high subject compliance, and would seem to indicate a minimal influence on the metabolism of lipids and carbohydrates in the small number of subjects studied.