Forearm bone density in users of Depo-Provera as a contraceptive method.

OBJECTIVE: To determine the influence of depot medroxyprogesterone acetate (MPA) on bone mineral density when used as a contraceptive method. DESIGN: Cross-sectional study. SETTING: Academic tertiary-care hospital. PATIENT(S): Fifty premenopausal women who had used depot MPA as a contraceptive method for > or =1 year and 50 women who had never used hormonal contraceptive methods. INTERVENTION(S): Bone mineral density was evaluated at the midshaft and at the distal radius of the nondominant forearm using single x-ray absorptiometry. MAIN OUTCOME MEASURE(S): Bone mineral density. RESULT(S): Bone mineral density at the midshaft of the forearm was lower in depot MPA users than in women who had never used hormonal contraceptive methods, but the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in the study group. The duration of depot MPA use was not related to bone mineral density. CONCLUSION(S): Women > or =35 years of age presented with a lower bone mineral density only at the distal portion of the forearm after the use of depot MPA for > or =1 year. However, this decrease was not related to the duration of depot MPA use. It is not possible to conclude that women who use depot MPA are at risk of osteoporosis.

PIP: The impact of depot medroxyprogesterone acetate use on bone mineral density was assessed in a cross-sectional study of 100 women recruited from a teaching hospital in Campinas, Brazil, during 1996-98. Bone mineral density, as evaluated at the midshaft and distal radius of the nondominant forearm by single x-ray absorptiometry, was compared in 50 women 35-45 years of age who had been using Depo-Provera for contraception for 1 year or more (mean duration, 46.4 +or- 38.6 months) but had never used any other hormonal method and 50 age- and weight-matched women who had never used any form of hormonal contraception. Although mean bone mineral density at the midshaft of the forearm was lower in Depo-Provera users than nonusers of hormonal contraception (0.459 +or- 0.042 vs. 0.474 +or- 0.049 g/sq. cm), the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in Depo-Provera users than nonusers of hormonal methods (0.362 +or- 0.040 vs. 0.392 +or- 0.049 g/sq. cm, p 0.001). The duration of Depo-Provera use was not related to bone mineral density, even when women had used the method for more than 5 years. Multiple regression analysis indicated that 4 pregnancies, White race, and Depo-Provera use were significantly associated with lower bone mineral density at the midshaft section of the forearm; at the distal section of the forearm, these variables were Depo-Provera use, more than 4 pregnancies, White race, older age at menarche, and habitual coffee drinking. These findings do not provide sufficient evidence to conclude that Depo-Provera users are at increased risk of osteoporosis.

[Contraceptive use in women with heart disease]. / Uso de contraceptivos em portadoras de cardiopatia.

PURPOSE: To analyse efficacy, tolerance and adverse events of reversible contraceptives in women with cardiac disease. METHODS: We studied prospectively during 24-39 (mean = 29) months, 89 women with heart disease with a mean age of 25.6 (16-42) years. Rheumatic heart disease was present in 73 (82%) cases, congenital heart disease in 11 (11%), coronary artery disease in 2 (2%) and cardiomyopathy in 3 (3%) case. The patients were divided in three groups: GCO--35 patients taking combined oral contraceptives (30 micrograms ethinyl estradiol and 75 micrograms gestodene--COs); GIT--27 using injectable progestagens (depot medroxyprogesterone acetate-DMPA) and GUID--27 with intrauterine device (IUD). RESULTS: In GCO occurred 4 (11.4%) cases of arterial hypertension, 1 (2.8%) of a transient cerebral isquemic attack, 3 (8.5%) of spotting, 1 (2.8%) of amnorrhea e 1 (2.8%) pregnancy. Interruption of this method occurred in 4 (11.4%) cases due to hypertension (2), pregnancy (1) and amenorrhea (1). In group GIT there were 2 (7.4%) cases of arterial hypertension, 18 (66.6%) of amenorrhea, and 3 (11.1%) of spotting. Interruption of use occurred in 5 (18.5%) due to amnorrhea (2), weight gain (2) and headache (1). In GUID there was 1 (3.7%) case of infeccion, 1 (3.7%) pregnancy and 1 (3.7%) spontaneous expulsion of IUD. Interruption of use took place in 3 (11.1%) cases due to infeccion, pregnancy and expulsion. The comparation between the groups demonstrated a difference in the incidence of amenorrhea (p < 0.005) and descontinuation of use of the method (p < 0.025). CONCLUSION: Use of reversible contraceptives in heart disease women was associated with an acceptable cardiovascular risk. Efficacy and side effects of the methods were comparable in the groups, however intolerance was more observed in GIT.

PIP: The aim of this study was to analyze efficacy, tolerance, and adverse events of reversible contraceptives in women with cardiac disease. The authors studied prospectively, during a period of 24-39 (mean = 29) months, 89 women with heart disease of mean age 25.6 (16-42) years. Rheumatic heart disease was present in 73 cases (82%), congenital heart disease in 11 (11%), coronary artery disease in 2 (2%), and cardiomyopathy in 3 (3%). The patients were divided into three groups: GCO--35 patients taking combined oral contraceptives (30 mcg ethinyl estradiol and 75 mg gestodene); GIT--27 patients using injectable progestagens (depot medroxyprogesterone acetate); and GUID--27 patients with IUDs. In the GCO group were found 4 cases (11.4%) of arterial hypertension, 1 (2.8%) of a transient cerebral ischemic attack, 3 (8.5%) of spotting, 1 (2.8%) of amenorrhea, and 1 (2.8%) of pregnancy. Interruption of this method occurred in 4 cases (11.4%): 2 due to hypertension, 1 due to pregnancy, and 1 due to amenorrhea. In the GIT group there were 2 cases (7.4%) of arterial hypertension, 18 (66.6%) of amenorrhea, and 3 (11.1%) of spotting. Interruption of use occurred in 5 cases (18.5%): 2 due to amenorrhea, 2 due to weight gain, and 1 due to headache. In the GUID group there was 1 case (3.7%) of infection, 1 (3.7%) of pregnancy, and 1 (3.7%) of spontaneous expulsion of the IUD. Interruption of use took place in 3 cases (11.1%): 1 due to infection, 1 due to pregnancy, and 1 due to expulsion. The comparison between the groups demonstrated a difference in the incidence of amenorrhea (p 0.005) and method discontinuation (p 0.025). Use of reversible contraceptives in women with heart disease was associated with an acceptable cardiovascular risk. Efficacy and side effects of the methods were comparable in the groups; however, intolerance was observed more in the GIT group. (author's modified)

Are Norplant, Depo-Provera good options for nursing mothers?

PIP: Family planning providers do not agree on whether it is good clinical practice to administer Norplant or Depo-Provera to mothers shortly after delivery. Manufacturers of both contraceptives recommend that providers not prescribe them before 6 weeks postpartum for lactating mothers. The hormones enter the breast milk, but the amount is minimal, and no studies show the small amount of hormones to be harmful. Some providers point to this lack of data as a reason to prescribe them to mothers immediately after delivery because progestin-only pills do neat adversely affect breast feeding. Some providers even claim Norplant should be inserted no later than 3 weeks. On the other hand, other providers, like a physician from Chile, stress that the lack of studies does not mean it is safe, just that there have not been enough studies. The Chilean physician is investigating the effect of hormones on infant health and central nervous system development. A nurse midwife at the University Medical Center in Jacksonville, Florida, reports that no woman using Depo-Provera has complained of breast-feeding problems. More than 50% of postpartum women leave this hospital after receiving an injection of Depo-Provera and those who do not come back for their 3-month injection are those who did not receive proper prenatal counseling about its side effects. The most upsetting side effect is bleeding which becomes less stressful with adequate counseling. Depo-provera extends the normal postpartum bleeding by a month. A director of services at a family planning clinic in San Marcos, Texas, notes that proper counseling, both before insertion and before removal, is also the key to proper management of Norplant acceptors. Providers at this clinic insert it 6 weeks postpartum. Hispanic women in San Marcos are concerned about bleeding because their partners do not want to have sex with a bleeding partner. Another side effect concerning clients is weight gain.^ieng

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.

Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica.

The relationship between cervical cancer and the use of depot-medroxyprogesterone acetate (DMPA) was examined in a nationwide case-control study in Costa Rica. Cases were women ages 25-58 years of age with invasive squamous cell cancer (N = 149) or carcinoma in situ (CIS, N = 415) reported by the National Tumor Registry during 1982-84. Controls (N = 764) were randomly selected during a nationwide household survey. Using logistic regression, we adjusted for known risk factors for cervical cancer. DMPA use was associated with a risk of CIS of 1.1 (95% confidence interval 0.6-1.8) and a risk of invasive cancer of 1.4 (95% confidence interval 0.6-3.1). The slightly elevated risks observed may be the result of chance or a detection bias. One limitation of this study is that few women had used DMPA for longer than two years.

PIP: A nationwide case-control study was conducted in Costa Rica in 1984-85 to examine the association between depot-medroxyprogesterone acetate (DMPA) and cervical cancer. Cases, restricted to women 25-58 years of age at the time of diagnosis, were women with invasive squamous cell cancer (n = 149) or carcinoma in situ (CIS, n=415) reported by the National Tumor Registry during 1982-84. The 764 controls were randomly selected during a nationwide household survey. On average, the CIS cases were younger than controls; the invasive cases were older than controls. Both case groups were more likely than controls to be of low socioeconomic status, to have become sexually active at a young age, to report a history of a sexually transmitted disease or pelvic inflammatory disease, and to report having 3 or more partners in their lifetime. Ever users of DMPA had a risk of CIS of 1.1 when compared with never users. Women who 1st used DMPA before age 30 had a CIS risk of 0.6 whereas users who began use after age 39 had a risk of 2.0. Both of these risk estimates were based on small numbers of users. Ever users of DMPA had a risk of invasive cancer of 1.4 when compared with never users, but all estimates for invasive cancer were based on only 10 cases who reported use of DMPA. Few of the women had used DMPA for longer than 2 years.

Invasive cervical cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

Preliminary results of a study of the possible relationship of depot-medroxy-progesterone acetate (DMPA) to invasive cervical cancer are presented. The findings are based on data from three participating centres in Thailand and one in Mexico. A relative risk for cervical cancer of 1.2 was observed in women who had ever used DMPA; this was not statistically significant. No consistent increase in risk with duration of use was observed, although a relative risk of 2 was found in women who had used DMPA for more than 5 years. This observed increase in risk was confined to women who were aged under 46 years or who had first been exposed to DMPA before 30 years of age. These findings are based on small numbers of subjects, and may not represent a causal relationship.

Breast cancer and depot-medroxyprogesterone acetate. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The preliminary results of a study of the incidence of breast cancer in relation to use of depot-medroxyprogesterone acetate (DMPA) are presented. The findings are based on data from three participating centres in Thailand, and one each in Kenya and Mexico. A relative risk for breast cancer of 0.7 was observed in women who had ever used DMPA; this was not statistically significant. Although no consistent decrease in risk with duration of use was observed, the lowest relative risk (0.5) was observed in women who had used DMPA for three or more years. These findings are based on small numbers and must be considered preliminary. However, they provide no evidence that DMPA increases the risk of breast cancer, and suggest that it may exert a protective effect, particularly in long-term users.

[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

[Acceptability of medroxyprogesterone acetate in rural areas of Mexico]. / Aceptabilidad del acetato de medroxiprogesterona en las áreas rurales de méxico.

PIP: 361 retrospective surveys were carried out among users of medroxyprogesterone acetate (MPA) given in a trimestral regimen of 150 mg/dose in rural areas of 3 Mexican states. Gynecology-obstetric antecedents, previous experience with oral contraceptives (OCs), effects of injections on the menstrual cycle, causes of method suspension, and opinion concerning administration of medication were analyzed. 78.6% of the patients were multigravidae with 4 or more pregnancies; 39.1% were former users of OCs, and 23.4% had stopped taking them because of side effects. The side effects of MPA on the menstrual cycle were: amenorrhea (19.8%); hemorrhage/cycle of 10-30 days in 14.7%; and hemorrhage/cycle of 30 or more days in 11.6%. Only 14.7% of users stopped the injections and of these, 80.3% did so due to menstrual cycle disorders. 99.7% of the users thought the method was comfortable as a family planning procedure. (author's)^ieng

Three-monthly Depo-Provera in Mexico.

PIP: From 1969 to 1975, 54,650 new acceptors over 30 years of age or with 4 or more children were administered 150 mg Depo-Provera by injection every 90 days. A total of more than 400,000 90-day cycles of clinical observation of the menstrual, metabolic changes, body-weight fluctuations, systemic side effects, and return of fertility were recorded. The rate of pregnancy was .35; the longer the time under treatment, the less abnormal bleeding and greater amenorrhea was noted. Weight gain was between 2-9 kg over 12-36 months. Pregnancy occurred 6-24 months after discontinuation of therapy to achieve pregnancy. Treatment did not affect lactation adversely. There was a continuation rate of 56% during the first 12 months and 54% in the following 18 months. Advantages of use are: 1) can be used on large scale, 2) can be alternative to sterilization, 3) is effective with a minimum of motivation, 4) does not affect lactation, 5) continuity rates are higher than those of oral contraceptives, 6) cost is low, 7) allows use of paramedical personnel, and 8) can be administered postpartum and postabortion.^ieng

Adverse effects of large doses of medroxyprogesterone (MPA) in idiopathic isosexual precocity.

PIP: Medroxyprogesterone (MPA) is a progestin with no clinically detectable estrogenic and androgenic properties used in the treatment of sexual precocity. This report presents the results of administering large intramuscular doses of MPA (200 to 300 mg every 7 to 10 days for periods ranging from 5 to 40 months) in 3 girls and 1 boy with rapidly progressing idiopathic sexual precocity (e.g., breast enlargement, penile enlargement, pubic hair growth). Urinary steroids were measured by bioassay, standard modification of the double isotope derivative method, and other standard methods. The MPA regimen suppressed the signs and symptoms of precocious puberty. The 3 girls did not have further menstrual flow, breast tissue regressed, uterine size decreased, and vaginal cornification diminished, although not to prepubertal levels. A marked decrease in frequency of erections, no further penile enlargement, and only minimal progression of sexual hair were observed in the boy (the testis continued to enlarge, however). Excessive weight gain, rapid rate of linear growth and skeletal maturation were observed in the children during treatment, as was blood pressure elevation. The effectiveness of MPA appears to be mediated by the suppression of pituitary gonadotropin secretion. However, there was no consistent reduction of urinary gonadotropin levels, and suppression of gonadal stimulation was incomplete. Evidence of drug toxicity precludes further administration of high dosages of MPA even for research purposes.^ieng

[Effects of various steroids on the morphology and function of human fallopian tubes]. / Acción de algunos esteroides sobre la morfología y la función de la trompa de falopio humana.

PIP: The contractability of the Fallopian tubes is instrumental in the transport of the ovum to the uterus. Various studies have been done to determine the effect of different hormones on this property of the tubes, but they have been inconclusive. 34 patients who were scheduled for salpingectomies for reasons of birth control and who had been using steroid contraceptives for at least 3 months prior to the operation were selected for study. Half the sample had used pure progestagens (Depo-Provera or chlormadinone) and half had used a combined preparation (quinestrol + quingestanol or deladroxate). All were between 29-41 years of age with numbers of pregnancies ranging from 5 to 21. The intensity and frequency of the contractions and the general activity of the isthmus portion of the tubes were studied for 10-minute periods in 2 cm segments. Also, histological studies were done using hematoxylin eosin tincture and Van Giessen tincture, and histochemical tests were performed. The 17 cases on combined orals exhibited a significantly higher rate of activity than those on pure progestins, but were also subject to contractions of greater intensity. The histochemical studies showed a decrease in the energetic material and in the enzymatic activity related to carbohydrate metabolism in the tubes of the progestin group. The depression of motor activity and energetic metabolism was, however, neutralized by administering estrogens.^ieng