Elsimar M. Coutinho

PROLONGED INTRAUTERINE CONTRACEPTION: A SEVEN-YEAR RANDOMIZED STUDY OF THE LEVONORGESTREL 20 mcg/DAY (LNg 20) AND THE COPPER T380 Ag IUDS

A levonorgestrel-releasing IUD and the Copper T 380Ag IUD were in randomized comparison for seven years in five clinics. In two other clinics the randomized study was truncated at five years, but use of the Copper T continued. No pregnancies occurred to users of either device in years 6 and 7. Cumulative pregnancy rates were 1.1 per 100 at seven years for the steroid-releasing and 1.4 per 100 for the copper-releasing IUDs. Cumulative rates of PID did not differ between devices. Infection rates appeared to be lowest during the sixth and seventh years of the study. Termination attributable to amenorrhea was the principal contributor to differences in cumulative continuation rates between devices. At the five clinics that carried the comparative study to seven years, cumulative continuation rates were 24.9 per 100 for LNg20 IUD users and 29.4 per 100 for TCu 380Ag users. Women who used either method for periods of five to seven years experienced, on average, marked to mild increases in hemoglobin as compared with levels at admission. The Copper T380 family and the LNg20 IUDs represent the most effective reversible contraceptive methods yet studied in long-term randomized trials.

Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the Copper T 380Ag intrauterine devices: A five-year randomized study

An intrauterine device, releasing approximately 20 micrograms/day of levonorgestrel (LNg 20), used by 1124 women, was studied in a randomized trial of five years duration in comparison with the Copper T, model TCu 380Agm in 1121 women. At five years, the gross cumulative pregnancy rate of 1.1 +/- 0.5 per 100 among users of the LNg 20 devices was not significantly different from the rate of 1.4 +/- 0.4 per 100 experienced by users of the Copper T 380Ag. The steroid-releasing IUD had significantly higher termination rates for expulsion and amenorrhea, a significantly lower termination rate for other menstrual problems and pain, and a lower continuation rate. The five-year continuation rate among women using the TCu 380Ag was 40.6 per 100 as compared with that of 33.0 per 100 among women randomized to the LNg 20 device (P less than .001). Terminations attributed to amenorrhea with the LNg device primarily account for differences in continuation. These two intrauterine devices are the most effective long-term, reversible IUDs yet reported in the literature. No other contraceptive methods have exhibited such low long-term pregnancy rates in randomized comparative trials.

Observations on the Antigenicity and Clinical Effects of a Candidate Antipregnancy Vaccine: β-subunit of Human Chorionic Gonadotropin Linked to Tetanus Toxoid* †

Observations on the antibody response and clinical effects of injection of purified beta-subunit of human chorionic gonadotropin covalently linked to tetanous toxoid were made in 15 healthy young women who had previously undergone tubal ligation. Antibodies detectable by radioimmunoassay were found in 14 of the women. Clinical surveillance and immunologic, hematologic, and biochemical tests indicated excellent local and systemic tolerance to the antigen. No significant adverse effects on menstrual function, endocrine status, or health were found.

Insertion of Mirena after Endometrial Resection in Patients with Adenomyosis

STUDY OBJECTIVE To evaluate the efficacy of Mirena, a levonorgestrel-releasing intrauterine device, after endometrial resection for treatment of menorrhagia caused by adenomyosis. DESIGN Open, randomized, observational study (Canadian Task Force classification II-2). SETTING Private hospital. PATIENTS Ninety-five women. INTERVENTION Endometrial resection, after which control patients received no further treatment and study patients had Mirena inserted immediately after the procedure. MEASUREMENTS AND MAIN RESULTS The rate of amenorrhea after 1 year was significantly higher in the Mirena group. Nineteen percent of women in the control group had a second procedure to control bleeding compared with none in the Mirena group. CONCLUSION Insertion of Mirena after endometrial resection is effective treatment for menorrhagia caused by adenomyosis and has very few adverse effects.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I-Use effectiveness. An international comparative trial.

Contraceptive vaginal rings (CVRs), with approximate daily release rates of 250-290 mcg of levonorgestrel and 150-180 mcg of estradiol and manufactured in a shell design, were studied for effectiveness and acceptability in multicentered trials involving 1103 ring users in Brazil, Chile, Dominican Republic, Sweden, U.S., Denmark/Finland, and Nigeria. A comparison group of 533 women used the oral contraceptive Nordette. Both 1st and all segment 1 year gross pregnancy rates among CVR users were less than 3/100, rates similar to Nordette users. Continuation at 1 year was 50/100 users of the ring (all segments) and 38/100 among Nordette users, more of whom were lost to follow-up. Gross 1 year rates of termination for medical reasons ranged from 25-29/100. Ring users were more likely to terminate for vaginal problems and pill users for headache, nausea, and associated reasons. These trials indicate that CVRs of this design are as effective and have continuation rates equal to and possibly superior to Nordette under the same study conditions.

Hysteroscopy and Transvaginal Sonography in Menopausal Women Receiving Hormone Replacement Therapy

STUDY OBJECTIVE To evaluate the endometrial cavity of menopausal women with irregular bleeding while receiving hormone replacement therapy. DESIGN Comparative evaluation of hysteroscopic and biopsy findings. SETTING A center for reproductive studies. PATIENTS Forty-one patients receiving different regimens of hormone replacement therapy. INTERVENTIONS Hysteroscopy, endometrial biopsy, and transvaginal sonography were performed in all 41 women. In 10 patients, endometrial polyps were removed with the resectoscope. MEASUREMENTS AND MAIN RESULTS Irregular bleeding during hormone replacement therapy was associated with atrophic endometrium whenever transvaginal sonography showed endometrial thickness to be less than 4 mm. In patients who developed increased endometrial thickness after hormone replacement therapy, hysteroscopy revealed the presence of endometrial polyps in the uterine cavity. Histopathologic examination of excised polyps revealed cystic or adenomatous hyperplasia confined to these lesions. CONCLUSIONS Endometrial polyps can appear in menopausal women receiving hormone replacement therapy despite the presence of progestins to oppose the action of estrogens.

Response of the nonpregnant uterus to vasopressin as an index of ovarian function

Abstract Investigations conducted with a sample of 89 normal menstruating women demonstrated that there is a relationship between phase of the menstrual cycle and uterine response to vasopressin. A positive response was detected during menstruation which became progressively less intense during the proliferative phase and shifted successively from absent to negative at midcycle. At the beginning of the secretory phase the negative response reverted to positive. Estrogen administration served to block this negative to positive change. Tests performed with menopausal women and an oophorectomized patient, for whom artificial cycles were produced, showed that estrogen allowed for the negative response to vasopressin and that progesterone domination was prerequisite for the shift from negative to positive response. The potential uses of the vasopressin response to evaluate ovarian function and to detect ovulation have been discussed. Comparative study with oxytocin indicated that either estrogen or estrogen plus progesterone is instrumental in producing a block to the effect of this oxytocic. The response to oxytocin was absent in the late proliferative phase and the early secretory phase, precluding the use of this hormone as a test for detecting ovulation.

Contraception with long acting subdermal implants: I. An effective and acceptable modality in international clinical trials

This paper presents results of a double blind, multi-centered and multi-national study of two progestin only subdermal implants used for contraception. A regimen of six capsules of levonorgestrel (Ng) used by 492 women had a net cumulative 12-month pregnancy rate of 0.6 percent and a continuation rate of 74.6 percent. 498 women used six capsules of norgestrienone (R2010) and experienced a net cumulative 12-month pregnancy rate of 3.5 percent and a continuation rate of 79.4 percent. The difference in the pregnancy rate was significant at P less than 0.01, while there was no significant difference in the continuation rates. Menstrual problems were the principal reason for termination of the levonorgestrel regimen, accounting for approximately half of all terminations. There were significantly fewer menstrual problems among users of the norgestrienone (R2010) capsules; the net cumulative 12-month termination rate for this reason was 4.3 percent. Results are compared with continuation and termination rates for acceptors of the Copper T 200 at the same clinics. The low pregnancy rate and reasonably high continuation rate of the norgestrel implants coupled with the fact that the expected effective lifetime of a set of capsules is of the order of 3-5 years appears to warrant further development of this contraceptive regimen.

Aromatase and cyclooxygenase-2 expression in endometrial polyps during the menstrual cycle

Objectives. To study the changes in aromatase, Ki-67 and cyclooxygenase-2 (COX-2) expression during the menstrual cycle in both endometrial polyps and normal endometria. Patients and methods. Paraffin-embedded tissue samples from 118 premenopausal patients were submitted to immunohistochemistry for measurement of aromatase, COX-2 and Ki-67 expression. Fifty cases of endometrial polyps and 68 cases of disease-free endometrium were included. Results. The presence of aromatase expression was significantly higher in endometrial polyps than in disease-free endometria. On the other hand, changes in COX-2 and Ki-67 expression followed a similar pattern during the menstrual cycle in both groups, expression peaking during the proliferative phase and falling during the late luteal phase. Conclusion. A significantly higher proportion of endometrial polyps express aromatase compared with disease-free endometrium; however, no correlation was found between aromatase expression and changes in either Ki-67 or COX-2 expression during the menstrual cycle.

A multicenter study of levonorgestrel—Estradiol contraceptive vaginal rings II — Subjective and objective measures of effects: An international comparative trial

Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination. Inquiries about changes in the frequency of specific conditions were made at the end of the subjects participation in the first year of the study. The incidence of spontaneous complaints was similar among users of the 2 different-sized rings and of the pill.