Bone density among long-term users of medroxyprogesterone acetate as a contraceptive.

The bone density (BD) of 72 women using depot-medroxyprogesterone acetate (DMPA) for at least 1 year was compared with that of 64 women who were not users of hormonal contraceptives. The BD of lumbar spine, femoral neck, Ward's triangle, and trochanter was measured by dual energy X-ray absorptiometry (DEXA-LUNAR DPX). Estradiol (E2) concentrations were measured by radioimmunoassay (RIA). The mean age of DMPA users and nonusers was 31.8 and 31.1 years, respectively. Mean E, was 55.7 pg/mL for users and 149.9 pg/mL for controls (p < 0.001). The BD was significantly lower for DMPA users than for controls in all sites (p < 0.01). In addition, young adult T-scores in the lumbar spine were significantly lower among DMPA users than in controls (p < 0.01). Differences were maintained in a subsample of 47 women per group paired by age and body mass index (BMI). Multiple regression analysis showed that older age, lower BMI, and longer amenorrhea were associated with lower BD in the femoral neck, whereas lower BMI and use of DMPA were associated with lower BD in the lumbar spine.

PIP: Family planning programs that offer depot medroxyprogesterone acetate (DMPA) cannot be indifferent to the risk of lowered bone density. A study conducted at the Family Planning Clinic of the State University of Campinas (Sao Paulo, Brazil) compared bone densities in 72 women who had been using DMPA for at least 1 year (mean duration, 42 months) and 64 regularly menstruating nonusers. Mean age was 31 years in both groups; there were no significant differences between the 2 groups in terms of ethnicity, body mass index (BMI), or smoking. Mean serum estradiol concentrations were 55.7 +or- 40.5 pg/ml for DMPA users and 149.9 +or- 88.2 pg/ml for nonusers (p 0.001). The mean length of amenorrhea was 26.5 +or- 23.8 months among DMPA users. The mean bone density in DMPA users was significantly lower than that of controls at all sites evaluated (i.e., lumbar spine, femoral neck, Ward's triangle, and trochanter). 38 DMPA users, compared with only 17 controls, had a T-score in the lumbar spine lower than -1 standard deviation (p = 0.014). Multiple regression analysis identified BMI and DMPA use as variables significantly associated with bone density in the lumbar spine; in the femoral neck, these variables were BMI, age, and length of amenorrhea. Periodic bone densitometry should be considered for women over 40 years of age with low BMI who have more than 2 years of continuous amenorrhea.

Introductory study of the once-a-month, injectable contraceptive Cyclofem in Brazil, Chile, Colombia, and Peru.

An introductory trial with the injectable contraceptive Cyclofem was carried out in Brazil, Chile, Colombia, and Peru, with participation by 3,183 women. Women were followed-up for up to 2 years of use and the data were evaluated by life table analysis. A total of 29,676 women-months were accumulated for up to 2 years. No pregnancies were observed in the 2 years. The discontinuation rates for amenorrhea in the first year ranged from 3.4 in Brazil to 8.1 in Colombia, and for menstrual disturbances from 5.1 in Chile to 9.2 in Brazil. The discontinuation rates for other medical reasons ranged from 7.8 in Brazil to 26.3 in Colombia, and for personal reasons from 17.2 in Chile to 23.5 in Brazil. Continuation rates ranged from 42.3 in Colombia to 52 in Chile. In the second year of observation the rates of discontinuation were lower than those observed in the first year, with the exception of personal reasons in Brazil, which were the same as those observed in the first year. Continuation rates ranged from 19.4 in Brazil to 36.8 in Chile. The comparison of reasons for discontinuation in selected clinics showed that the rate for amenorrhea in one clinic in Chile was more than three times that in others and in Peru was seven times more in one clinic than in another. Regarding menstrual disturbances, in Peru one clinic presented a rate three times higher than the others. The main reasons for discontinuation due to other medical reasons were headache and weight gain. In conclusion, Cyclofem presented a high contraceptive efficacy and an acceptable rate of continuation and discontinuation for up to 2 years in the four countries.

PIP: The performance of the monthly injectable contraceptive, Cyclofem, was evaluated in an introductory trial involving 3183 women recruited from family planning centers in Brazil, Chile, Colombia, and Peru. A total of 29,676 women-months of use were accumulated during up to 2 years of follow-up. No pregnancies occurred during the study period. Discontinuation rates per 100 women in the first year ranged from 3.4 in Brazil to 8.1 in Colombia for amenorrhea and from 5.1 in Chile to 9.2 in Brazil for menstrual disturbances. The discontinuation rate for other medical reasons (primarily headache, weight gain, and acne) ranged from 7.8 in Brazil to 26.3 in Colombia and for personal reasons from 17.2 in Chile to 23.5 in Brazil. First-year continuation rates ranged from 42.3 in Colombia to 52.0 in Chile. In the second year of use, continuation rates ranged from 19.4 in Brazil to 36.8 in Chile. Upon receiving these results, national regulatory authorities in the 4 participating countries approved Cyclofem registration. Acceptance of injectable contraception, which currently entails administration of the method by a service provider and travel to a clinic, could be improved in developing countries by training in self-administration.

Injectable contraceptives and risk of invasive cervical cancer: evidence of an association.

In a case-control study conducted in Latin America, the relationship of injectable contraceptive (IC) use to risk of invasive cervical cancer was analyzed while controlling for a variety of other risk factors, including female and spouse sexual behavior and infection with human papillomaviruses (HPV). Thirty-two cases and 82 controls reported ever having used IC. Women reporting use of IC for less than 5 years had an adjusted RR of 0.5 (95% Cl = 0.3-0.9), but users for 5 or more years had an RR of 2.4 (95% Cl = 1.0-5.7). The effect of prolonged IC use was stronger for women reporting first use 10 or more years before interview (adjusted RR = 3.4, 95% Cl = 1.1-24.9) and more than 5 years since last use (adjusted RR = 5.3, 95% Cl = 1.1-10.0). Cervical cancer risk associated with prolonged IC use was particularly high among women who reported never having had a Pap smear or having had one 2 or more years before interview (adjusted RR = 6.3, 95% Cl = 2.1-18.7). The reduced cervical cancer risk associated with short-term use of IC may reflect intensive Pap smear screening as the method is initiated. Although hampered by small numbers, these results suggest an adverse effect of prolonged IC use on cervical cancer risk, particularly among women who cease participation in screening programs after terminating usage, and indicate that long-term IC users should be monitored for cervical disease until more conclusive results are available.

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

[Injectable contraception using depot progestagens]. / Anticoncepción inyectable con progestágenos de depósito.

PIP: After 20 years of clinical experience, injectable hormonal contraceptives such as norethisterone enanthate (NET) and medroxyprogesterone acetate (MPA) remain one of the most controversial methods currently used for temporary control of fertility in women. Since December 1980 this controversy has been accentuated in Mexico with issuing of regulations by the Secretary of Health and Welfare which initially did not permit promotion of long-acting injectable hormones for contraception purposes, and later, in June 1981, a reconsideration which exclusively authorized use of NET as an injectable contraceptive. Undeniably these official measures and the scientific information, occasionally contradictory, have created confusion about the indications and risks of using these formulations in clinical work. This paper presents an anlysis of the basic pharmacological aspects of long-acting contraceptive progestagens, potential risks for side effects, and some clinical rules for safe use. The authors conclude that injectable contraceptives will continue holding a definite place among hormonal methods of temporary fertility control, particularly with the advent of new administration schemes for NET which have elevated its contraceptive efficacy without appreciably increasing complications. The more rapid metabolism of NET, manifested in the absence of significant effects on body weight, less alteration of the menstrual cycle, and more rapid return of fertility after discontinuation, has considerably increased its popularity, and the possibility exists that with time and an increase in clinical experience, it may replace MPA as the injectable contraceptive of choice. Nevertheless, while investigative studies have not clearly defined the possibilities of potential risk of using these contraceptives, its clinical use must be governed by appropriate selection and careful follow-up of patients.^ieng

[Use and effectiveness of norethisterone enanthate for family planning in a rural area]. / Uso y efectividad del enantato de noretisterona para la planificación familiar en el área rural.

PIP: The objective of this study was to analyze the acceptability, effectiveness, and continuation of long-acting progestagens in certain sectors of the population where its advantages are more obvious by virtue of certain socioeconomic, cultural, and geographic characteristics, and by lack of availability of family planning services, as in rural areas and urban marginal zones. The study was performed using females of reproductive age residing in rural areas of the Mexican States of Hidalgo, Puebla, and Yucatan between July 1981 and September 1982. Originally the investigation included a total of 462 women, of whom 94 were lost to follow-up, leaving a total of 368 patients (79.6%) with effective follow-up. The contraceptive used was 19-Nor progestagen, norethisterone enanthate (NET), in 200 mg doses administered intramuscularly. The 1st dose was applied between the 1st to the 5th day of the menstrual cycle and each 60 calendar days thereafter. Of a total of 94 discontinuations, 2/3 occurred during the 1st 6 months of the study. The final discontinuation rate was 14.46%. The studied population showed a continuation rate of 85.54% after 12 months of use. Observing rates by reasons for discontinuation, the principal causes in descending order were nonmedical reasons, amenorrhea, pregnancy, bleeding and other secondary effects. The greatest number of discontinuations, considering each particular reason, occurred predominantly during the 1st 6 months of the study. Distribution of users by age group show that more than 2/3 (71.8%) were between 20 and 34 years old. Distribution by number of previous pregnancies show 56.5% with 5 or more gestations. To analyze behavior of menstrual cycles, "cycles" were defined as period of 30 calendar days. Under this concept, more than 2/3 (70.9%) of the users had from 1 to 7 days of bleeding per cycle. On the basis of the results of the study, it is possible to conclude the following: 1) Continuation of NET use is greater than that observed with other long-lasting progestagens. This seems to be especially so when employed in areas where limitations exist for the utilization of other contraceptive means. 2) Contraceptive effectiveness is greater when administration is scheduled at 60 day intervals rather than longer intervals. 3) Unlike other long-acting progestagens, NET conserves the normal menstrual pattern in the majority of users, which favorably influences its continuation.^ieng