Ultrasonographic and endocrine evaluation of ovarian function among Norplant implants users with regular menses.

With the objective of evaluating the ovulatory function among long-term Norplant implants users with regular menstrual cycles, we undertook this prospective study including 11 Norplant implants users and 11 control women who were not using hormonal methods of fertility control. Exposed and unexposed women had had at least three regular menstrual cycles preceding enrollment. All women were followed during one menstrual cycle by serial vaginal ultrasound and estradiol (E2), progesterone (P), LH, and FSH measurements. Three Norplant implants users ovulated, three had luteinization of an unruptured follicle (LUF), three had persistent follicle growth up to a mean of 33 mm without rupture, and two had no follicular development beyond 16 mm. Ten of the controls had normal ovulation and one had LUF. Mean peak LH and FSH among Norplant implants users who ovulated were three- to four-fold lower than among controls. Although users of Norplant implants with regular cycles frequently have luteal activity, the results of this study suggest that elevation of P during the second half of the cycle does not necessarily indicate ovulation has occurred and may frequently be associated with the presence of luteinized unruptured follicle. When ovulation occurs, there are usually abnormal hormone levels (low LH/FSH peak, low progesterone) which may also contribute to the contraceptive effect of Norplant implants.

Effect of preovulatory insertion of Norplant implants over luteinizing hormone secretion and follicular development.

OBJECTIVE: To determine whether the process of ovulation could be interrupted by the insertion of Norplant implants (Leiras Pharmaceuticals, Turku, Finland) in the advanced preovulatory phase. DESIGN: Prospective study. SETTING: The Department of Biomedical Research at the Family Planning Clinic of PROFAMILIA, Santo Domingo, Dominican Republic. PATIENTS: Healthy women of reproductive age, requesting Norplant implants contraception. Thirteen of 15 women volunteers who were admitted completed the study. INTERVENTIONS: Norplant implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based on serial vaginal ultrasounds (US) beginning on day 10 of the cycle. Blood samples for determination of E2, P, LH, and levonorgestrel, were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred at 72 hours after insertion, blood sampling and US were done three times per week during 2 additional weeks. RESULTS: Follicle rupture occurred in 11 of 13 subjects within 72 hours after insertion, with the exception of 1 subject in whom rupture occurred between 72 and 192 hours. Two women already had an LH peak at the time of insertion. In 9 of the remaining 11 women, a shortlasting, blunted LH surge was observed at 4 hours postinsertion. In the remaining two women, who had the lowest E2 levels, ovulation was inhibited, and a persistent follicle developed without luteinization. CONCLUSIONS: The insertion of Norplant implants in the advanced follicular phase will not inhibit ovulation if sufficient E2 priming has occurred. On the contrary, the exogenous progestin may rapidly foster ovulation shortly after.

PIP: 15 healthy women of reproductive age requesting Norplant were admitted into this prospective study conducted to determine whether the ovulation process can be interrupted by the insertion of Norplant implants during the advanced preovulatory phase. The implants were inserted when the dominant follicle reached a mean diameter of 16 mm, based upon serial vaginal ultrasounds (US) beginning day 10 into the cycle. Blood samples to determine levels of E(2), P, LH, and levonorgestrel were taken and vaginal US performed at 0, 4, 24, 48, and 72 hours after insertion. If follicle rupture had not occurred by 72 hours after insertion, blood sampling and US were done three times per week for two additional weeks. Follicle rupture occurred in 11 of the 13 subjects who completed the study within 72 hours after insertion, except for one subject who experienced rupture at 72-192 hours. Overall, it was determined that the insertion of Norplant implants during the advanced follicular phase will not inhibit ovulation if sufficient E(2) priming has occurred. The exogenous progestin, however, may rapidly foster ovulation shortly thereafter.

Hormonal treatment for bleeding irregularities in Norplant implant users.

OBJECTIVE: Our purpose was to evaluate whether prolonged or irregular bleeding during Norplant implant use could be alleviated with the use of oral hormonal medication. STUDY DESIGN: One hundred fifty users of the Norplant levonorgestrel contraceptive implant with prolonged or frequent bleeding were enrolled in this prospective, randomized, comparative study and assigned to one of three treatment groups for 20 days: ethinyl estradiol 50 microg, an oral contraceptive (50 microg ethinyl estradiol and 250 microg levonogestrel), and placebo. Total days of bleeding during treatment and length of the bleeding-free interval were analyzed. RESULTS: Women treated with the levonorgestrel-ethinyl estradiol pill bled an average of 2.6 days during treatment compared with 5.4 and 12.3 days in the ethinyl estradiol and placebo groups, respectively. Differences between both hormonal groups and placebo were significant (p <0.00001); moreover, the combined pill was more effective than ethinyl estradiol along (p <0.0001). CONCLUSION: The combined pill proved to be an excellent palliative treatment and is a more practical approach because of availability at all clinic sites.

PIP: In the Dominican Republic, clinical researchers randomly assigned 150 users of the contraceptive implant Norplant who came to Profamilia's Family Planning Clinic in Santo Domingo complaining of bleeding irregularities to one of three treatment groups. They aimed to evaluate the effectiveness of a combined oral contraceptive (OC) with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol (EE) and of 50 mcg EE alone in treating bleeding irregularities. Bleeding irregularities were defined as prolonged bleeding (i.e., 8 or more continuous days of bleeding or spotting) or irregular bleeding (i.e., current bleeding episode initiated after a bleeding-free interval of less than 15 days). Age, parity, duration of Norplant use, and length of bleeding episode before treatment were similar in all three groups (i.e., OC, EE, and placebo). The OC group was significantly more likely to experience ceased bleeding within three days than the two other groups (91% vs. 67% for EE group [p 0.01 from OC group] and 15% for placebo group [p 0.0005 from both treatments]). Bleeding lasting for at least one week occurred less often in the OC group than the two other groups (2% vs. 14% for EE group and 50% for placebo group [p 0.0005 for both treatments]). Duration of bleeding was significantly lower in the OC group than the other two groups (2.6 days vs. 5.4 days for EE group and 12.3 days for placebo group; p 0.0001). Even though women in both hormonal treatment groups were more likely to experience gastralgia or nausea than the placebo group (33-40% vs. 4%; p 0.005), the side effects rarely interrupted treatment. These findings suggested that the OC is a very good effective treatment for bleeding irregularities and is a practical treatment since it is available at all Profamilia clinic sites.