Triphasic Oral Contraceptives Research Articles

Ovarian function is effectively inhibited by a low-dose triphasic oral contraceptive containing ethinylestradiol and levonorgestrel

For various metabolic and clinical reasons, it has been strongly advocated to reduce the dose of both the estrogen and progestogen components of oral contraceptives (OCs). In this study, we compared after 6 months of treatment, the action on various hormonal parameters of a standard-dose combined OC containing ethinylestradiol (EE) 0.050 mg and levonorgestrel (LNg) 0.250 mg and a low-dose triphasic combination containing a 59% reduced amount of the same steroids. Hormonal measurements in the last 3 days of OC intake indicated that basal levels of FSH and LH were less inhibited by the low-dose preparation, while PRL levels were unchanged. However, gonadal function was effectively inhibited by both high and low dose OCs, as demonstrated by equally low levels of E2, E1, P and 17-P. Consequently, no residual gonadal function could be anticipated from the observed low steroid concentrations. These results corroborated other studies (reviewed in this paper) in which serial hormonal measurements also revealed a complete lack of follicular maturation during low-dose triphasic OC treatment. Moreover, inhibition of circulating levels of A, DHEA, DHEAS, free T and DHT was similarly obtained with both preparations. Collectively, these data indicate that ovarian function is as effectively inhibited by a low-dose triphasic preparation as by a higher, standard-dose OC containing the same steroids.

Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel

The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): Trigynon R (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); Marvelon R (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and Ovidol R (n = 10), a sequential OC containing higher doses (50 νg) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol>Marvelon>Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged. Collectively, these data indicate that ( a) all three OCs are effective ovulation inhibitors, ( b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, ( c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and ( d) free testosterone levels are equally well suppressed by all three Ocs.

Clinical experience with a triphasic oral contraceptive ('Trinordiol') in young women.

Seven hundred and fifty cycles of treatment with a new triphasic oral contraceptive (WL-49(50). 'Trinordiol') containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years), 70% of whom had regular, normal cycles. Sixty-five percent had not used contraception before; the others had previously been on combined or progestagen-only oral contraceptives or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. No pregnancy was recorded during the 750 cycles of treatment. Fifteen (20%) women dropped out of the study for medical reasons, essentially breast tenderness, weight increase, spotting and nausea, in decreasing order of frequency. Mastalgia was present in 21% of the women (8.9% of the cycles) during triphasic oral contraception, but this symptom disappeared in more than half of the cases within 3 months of continued use. Other side-effects were less frequent: vaginal discharge (4.4% of the cycles), nausea (3.7%), abdominal and leg cramps (2.8%), headaches (3.2%) and weight increase (3%). Spotting and breakthrough bleeding were reported during only 1.9% of the cycles, a remarkably low frequency. No absence of withdrawal bleeding was noted. Weight and blood pressure changes were minimal and never reached statistical significance. Hypertension developed during triphasic medication in 1 predisposed individual. Complaints of oestrogen-related symptoms such as breast tenderness and digestive disorders were probably due to the reduced progestagen content of the preparation compared with combined low fixed daily dose oral contraceptives. However, no increases in dysmenorrhoea and/or premenstrual tension were noted. It is concluded that the triphasic preparation provides effective contraception with excellent cycle control and minimal side-effects, which should help to increase the acceptability of low-dose combined oral contraceptives.

Triphasic Oral Contraceptives

The triphasic oral contraceptive (OC) delivers the combined estrogen and progestogen components in 3 distinct incremental dosage regimens. This permits a reduction in total hormone content and provides safe and reliable contraception with fewer side effects. Monophasic OCs contain both an estrogen and progestogen in a fixed amount taken for 21 days. The dosages chosen in the early monophasics markedly suppressed endogenous estrogen and progesterone levels thereby also blocking ovulation. But the high amount of steroid hormone used presented a drawback. Biphasic approaches reduced the risk of side effects by decreasing steroid content and mimicking the menstrual cycle with the biphasic design. This pattern divides the regimen in 2 and consists of low levels of estrogen and progestogen in the 1st or follicular phase with increased steroids in the second or luteal phase. This method fails to consider the critical timing of the ovulatory phase and has resulted in OCs that may give inconsistent inhibition of ovulation and poor bleeding patterns making them less acceptable clinically. The triphasic approach more closely approaches the normal physiological system. The 1st phase provides low doses of estrogen and progestogen the 2nd phase increases the hormone and preempts the natural preovulatory surge of estrogen and luteinizing hormone. The key to the success of the triphasic is the timing of phase 2. The 3rd phase provides increased progesterone and lower estrogen to mimic the natural luteal phase. When counseling patients regarding triphasic OCs it is necessary to emphasize the importance of patient compliance and that the OCs be taken at the same time every day.