Medroxyprogesterone acetate [Depo Provera] injections. Development of striae.

A young girl developed extensive striae while on Depo Provera injections. She had gained some weight during the treatment. Endocrinal investigations were negative. The development of striae was attributed to her weight gain.

PIP: This case report presents a 20-year-old woman with extensive striae while on Depo-Provera injections. She attended the family planning clinic requesting Depo-Provera injection because she was feeling nauseated while on the combined oral contraceptive pill. Following the first injection, striae developed and a weight gain of 3.1 kg was noted. At this point, the stretch marks were attributed to the weight gain and dietary advice was given. However, in her second dose of Depo-Provera, her striae had now become quite florid and were distributed on her abdomen, upper arms, thighs, buttocks, back, and legs. Moreover, her weight had increased by a further 2.6 kg; no other symptoms were reported. Following her dietary discussion, she decided to switch to a progesterone-only pill. On her next visit the following month, she was continuing to gain weight. Endocrine investigations were negative; hence, the development of striae was attributed to her weight gain. A search through Pharmacia and Upjohn, manufacturers of the contraceptive injection, showed very few reported cases of striae following Depo-Provera injection. Furthermore, for most cases no opinions were provided as to the cause, and the outcome of events was not reported or was not known.

The effect of one injection of Depo-Provera on the human vaginal epithelium and cervical ectopy.

Two studies in rhesus monkeys have shown that progesterone implants, Depo-Provera and Norplant, were associated with vaginal thinning. Progesterone implants have also been associated with an increased risk of simian immunodeficiency virus (SIV) acquisition. This study in 16 women was done to assess vaginal epithelial thickness and number of cell layers from biopsies taken in the untreated follicular and luteal phases, and at 1 month and 3 months after administration of Depo-Provera. There was no significant change over time in either parameter from biopsies obtained in the luteal phase compared with those at either time after Depo-Provera administration. There was also no change in the mean number of Langerhans cells in vaginal wall specimens and no change in cervical ectopy. It appears that women do not respond to exogenous progestins with the dramatic vaginal thinning seen in rhesus monkeys.

PIP: This study assesses vaginal epithelial thickness and number of cell layers from biopsies taken in the untreated follicular and luteal phases and at 1 month and 3 months after administration of Depo-Provera. Subjects were seen at the CONRAD Clinical Research Center at the Eastern Virginia Medical School, Norfolk, Virginia. Findings showed that there was no significant change over time in either parameter from biopsies obtained in the luteal phase compared with those at either time after Depo-Provera administration. There was also no change in the mean number of Langerhans cells in vaginal wall specimens and no change in cervical ectopy. The dramatic vaginal thinning seen in rhesus monkeys was not observed among these subjects.

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.

PIP: This study presents a review of current clinical evidence on the usefulness of Depo Provera (medroxyprogesterone acetate, DMPA), a long-term method of reversible contraception. It is taken as an intramuscular long-acting agent (150 mg every 12 calendar weeks). The user failure rate approaches the method failure rate, which varies considerably with age. In terms of metabolic effects, it did not show changes in cholesterol or triglycerides and had no significant effect on hemostasis, which impairs the oral glucose tolerance test (OGTT) glucose response and increases insulin response. There were no significant adverse effects on long term growth and development in DMPA exposed children and no delays in return to fertility. For cancers, controlled surveillance of DMPA users found no overall increased risk of ovarian, liver or cervical cancer and even found a prolonged protective effect in reducing the risk of endometrial cancer. However, increased risk of breast cancer in recent users was observed; this could be due to enhanced detection of breast tumors of women using DMPA. The main DMPA disadvantages are menstrual disturbance and weight gain after 1 year. Bone mineral density (BMD) is found to be significantly lower. DMPA patients' sociodemographic characteristics and behavior placed then at higher risk for adverse pregnancy outcome in low infant birth weight and also possibly in polysyndactyl and chromosomal defects. Thus, for injectable progestogen, the data is again less conclusive. Risks may be similar to POP (progestogen-only contraceptive pill), but did not reach significance in the meta-analysis.

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.

Decline in bone mineral density with stress fractures in a woman on depot medroxyprogesterone acetate. A case report.

BACKGROUND: Depot medroxyprogesterone acetate is a popular contraceptive among young, physically active women. However, its administration has been linked to a relative decrease in estrogen levels. Since bone resorption is accelerated during hypoestrogenic states, there has been growing concern about the potential development of osteoporosis and fractures with the use of this contraceptive method. CASE: A physically active, 33-year-old woman demonstrated a 12.4% drop in femoral neck bone mineral density (BMD), 6.4% drop in lumbar BMD and 0.8% drop in total BMD with the subsequent development of a tibial stress fracture while on depot medroxyprogesterone acetate. Bone mineralization rapidly improved, and the stress fracture resolved with discontinuation of the medication. CONCLUSION: The long-term effects of depot medroxyprogesterone acetate on bone mineralization in physically active women should be evaluated more thoroughly.

PIP: This case report illustrates the potential development of osteoporosis and fractures with the use of depot medroxyprogesterone acetate (DMPA), a popular contraceptive among young women. The case of a physically active 33-year-old woman who received 150 mg DMPA intramuscularly every 10 weeks, for a total of 3 injections, is presented. She demonstrated a 12.4% drop in femoral neck bone mineral density (BMD), a 6.4% drop in lumbar BMD, and a 0.8% drop in total BMD with the subsequent development of a tibial stress fracture while on DMPA. Bone mineralization rapidly improved, and stress fracture resolved with discontinuation of the medication. Women using DMPA are in a state of relative estrogen deficiency, which may not be adequate to maintain BMD in some patients. The long-term effects of DMPA on bone mineralization in physically active women should be evaluated more thoroughly.

Long-term depot medroxyprogesterone acetate (Depo-Provera) use in inner-city adolescents.

PURPOSE: To determine Depo-Provera continuation rates and reasons for its discontinuation among adolescents. STUDY DESIGN: Medical record reviews and telephone interviews with 159 adolescents who initiated Depo-Provera use between 1 December 1992 and 31 December 1995 at two clinics in New York City. Depo-Provera continuation was measured using lifetable analysis. RESULTS: The mean age was 17.7 +/- 1.5 years, with a median of 1 pregnancy (range 0-11). Mean follow-up was 23.4 +/- 10.7 months. Depo-Provera continuation rates were 71% at 3 months, 48% at 6 months, and 27% at 12 months, and were not affected by age, race, pregnancy or contraceptive history, clinic, or foster care status. Forty-three subjects (37% of discontinuers) restarted Depo-Provera during the study period, with a mean time to restart of 8.4 months after the last Depo-Provera injection. Side effects were the main reported reason for Depo-Provera discontinuation, primarily menstrual irregularities (26%) and weight gain (18%). Seventy percent of those discontinuing Depo-Provera owing to irregular bleeding did so after only one injection. For 23%, the single reason for discontinuation was appointment noncompliance. Restart rates were lowest among those who reported irregular bleeding (15%), weight gain (9%), and hair loss (10%), and highest among those discontinuing owing to missed appointments (87%) (p < 0.05). Pregnancies occurred in 19% of Depo-Provera discontinuers. CONCLUSION: Although Depo-Provera continuation rates among adolescents are low, over a third of discontinuers may restart the method. Aggressive management of side effects and assistance with appointment follow-up may improve long-term use. High pregnancy rates warrant close follow-up after Depo-Provera discontinuation.

PIP: Depo-Provera continuation rates and reasons for discontinuation among low-income US adolescents were investigated through a review of the records of the 159 teens who initiated use of this method at two inner-city clinics in New York City, New York (US), during 1992-95. At both study sites, Depo-Provera was available as a family planning option without parental consent. Mean age of acceptors was 17.7 years, with a median of one prior pregnancy. Almost all were unmarried, Black or Hispanic, and Medicaid recipients. At follow-up (mean duration, 23.4 months), only 21 teens (13%) were still using Depo-Provera; 115 (72%) had discontinued use and the remaining 23 had been lost to follow-up. The median duration of Depo-Provera use was 6.9 months. Continuation rates were 71% at 3 months, 48% at 6 months, 27% at 12 months, and 15% at 18 months. Side effects, especially menstrual irregularities (25%) and weight gain (19%), were the main reason for Depo-Provera discontinuation. 70% of those discontinuing the method for irregular bleeding did so after only one injection. Another 23% discontinued because of problems keeping appointments. Methods adopted after Depo-Provera discontinuation included oral contraceptives (31%) and condoms (21%); pregnancies occurred in 19% of discontinuers. 43 teens (37% of discontinuers) restarted Depo-Provera during the study period, after a mean interval of 8.4 months following the last injection. Restart rates were highest among those discontinuing due to missed appointments (87%) and lowest among those reporting irregular bleeding (15%), weight gain (9%), or hair loss (10%). Recommended, to improve Depo-Provera compliance among adolescents, are strategies to motivate attendance at follow-up appointments and manage method-related side effects.

Depressive symptoms and Depo-Provera.

Women enrolled in a multicenter prospective study were evaluated to identify any possible relationship between depressive symptoms and the use of contraceptives. Women choosing Depo-Provera (n = 495) were evaluated before starting these contraceptives and were reinterviewed 1 year later. Women who continued the method had lower depressive symptom scores at baseline than did the women who discontinued the method or who were lost to follow-up. Among the continuing Depo-Provera users, the depressive symptom scores improved slightly at 1 year (7.4 vs 6.7). Those subjects with the highest (i.e., worst) scores at enrollment demonstrated improved scores at follow-up.

PIP: The product labeling for Depo-Provera cites depression as an infrequent side effect. Previous research on this topic has documented self-reported depression or mood changes in 1-5% of Depo-Provera users. These studies were limited, however, by a lack of measurement of baseline depression. In the present study, 495 new acceptors of Depo-Provera enrolled in a broader prospective cohort study conducted at three US hospitals (Texas, Pennsylvania, New York) were interviewed at enrollment and again after 12 months of use. Included in both the initial and follow-up questionnaires were six questions on depressive symptoms in the past month taken from the Mental Health Inventory. At 12 months, 172 women were still using Depo-Provera, 221 had discontinued the method, and 102 were lost to follow-up. Women who were still using Depo-Provera at 12 months had lower depressive symptom scores at baseline than women who discontinued use or were lost to follow-up. Between baseline and the 12-month follow-up, the mean depression score dropped from 7.4 to 6.7 among continuing users and remained steady at 8.0 among discontinuers. The mean depression score in the quintile of women with the highest depression scores at baseline also decreased after 12 months of use, from 15.4 to 9.5. These results suggest that Depo-Provera use is not likely to exacerbate symptoms in women with pre-existing depression.

Adolescent satisfaction with postpartum contraception and body weight concerns.

PURPOSE: To explore factors that could be related to adolescents' satisfaction with postpartum contraceptives. METHODS: Three focus groups were conducted with a total of 22 adolescent mothers. The groups covered four content areas: feelings about birth control since becoming a mother, decision making about contraceptive use, factors that would influence contraceptive discontinuation, and the perceived side effects of the current contraceptive. Audiotapes from the groups were analyzed to identify major themes. RESULTS: Nineteen subjects received Depo-Provera when they were discharged after delivery and the majority reported that menstrual irregularities and weight gain were side effects. Two body weight-related themes were dominant: dissatisfaction with heavier than desired body weights and resignation about not returning to prepregnancy weights. CONCLUSIONS: Depo-Provera may be an effective contraceptive for adolescent mothers who are generally at high risk for rapid repeat pregnancy. This qualitative study suggests that contraceptive continuation may be enhanced with specific counselling to manage body weight concerns.

PIP: Factors having a potential effect on adolescents' use of and satisfaction with postpartum contraceptive methods were assessed in three focus groups involving 22 adolescent mothers of an infant under 12 months of age recruited from a Minnesota (US) clinic specializing in the prenatal and postpartum care of adolescent women. The average age of study participants was 17 years (range, 13-19 years). All adolescents chose to use contraception after delivery. 16 (73%) were using Depo-Provera, 3 were using oral contraceptives, and 3 were using condoms/foam. Most Depo-Provera users made their decision to accept this method with their prenatal care provider during pregnancy. Many had taken the pill at some point, but reported it was hard for them to take it every day. Despite concerns about side effects (especially increased hunger/weight gain and irregular menstrual bleeding), adolescent Depo-Provera acceptors preferred this method because it did not require daily compliance. 16 women (73%) considered themselves overweight, and they attributed this to both their pregnancy weight gain and their contraceptive method. Skepticism regarding their ability to lose weight through healthy eating and exercise was widespread. However, the desire to prevent another pregnancy through use of an effective method such as Depo-Provera was stronger than the desire to return to one's pre-pregnancy body weight. Overall, these adolescent mothers seemed resigned about their inability as a result of the demands of motherhood to resolve their malaise, fatigue, and sense of not being physically fit. These findings suggest a need for effective weight management and health-promoting programs for adolescent mothers that take into account their multiple role demands and generally limited financial resources.

Effectiveness of Cyclofem in the treatment of depot medroxyprogesterone acetate induced amenorrhea.

A total of 100 women who were using depot medroxyprogesterone acetate (DMPA) for contraception and who had experienced at least 6 months of drug induced amenorrhea, were randomized to either switching their method of contraception to Cyclofem, or continuing with DMPA. At the end of 6 months, 82% of the Cyclofem users had experienced some vaginal bleeding, compared with 10% of DMPA users. Time to resumption of vaginal bleeding was related to the duration of DMPA use to the duration of DMPA induced amenorrhea, and to the body mass index of the user. Over the 6 months of follow-up, 94% of Cyclofem users complained of some side effects, compared with 22% of DMPA users. The most frequently cited problems among Cyclofem users included breast tenderness, abdominal pain, and dysmenorrhea; yet a third of these women opted to stay on Cyclofem at the end of the study. It is concluded that switching to Cyclofem is a new option for DMPA users who are concerned about amenorrhea. Although using Cyclofem in this setting will not meet the needs of all such women, its effectiveness in inducing vaginal bleeding justifies a trial in those who have no contraindication to estrogen treatment.

PIP: Substantial numbers of women experience amenorrhea while using the injectable contraceptive depot medroxyprogesterone acetate (DMPA) and this represents a major cause of method discontinuation. In the present study, 100 DMPA acceptors from Bangkok, Thailand, with a history of at least 6 months of drug-induced amenorrhea were randomly assigned to switch their contraceptive method to Cyclofem (a combination of 25 mg of DMPA and 5 mg of estradiol cypionate) or continue with DMPA (150 mg). After 6 months, 82% of Cyclofem users compared with only 10% of DMPA users had experienced some vaginal bleeding. The median time to resumption of vaginal bleeding was 8 weeks in the Cyclofem group. Resumption time was related to the duration of DMPA use, the duration of DMPA-induced amenorrhea, and the user's body mass index. Although 94% of Cyclofem users compared with only 22% of DMPA users experienced minor side effects (breast tenderness, abdominal pain, dysmenorrhea) during the 6-month study period, 34% of these women elected to remain on Cyclofem at the end of the study. On the other hand, 90% of DMPA users opted to continue method use despite amenorrhea. The proven efficacy of Cyclofem justifies a trial in DMPA users concerned about their amenorrhea. This regimen can be expected to induce vaginal bleeding in more than 80% of users after 1-3 months of treatment.

The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women.

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA), an injectable progestogen, is a widely used contraceptive acting primarily by inhibiting secretion of pituitary gonadotrophins, thus producing oestrogen deficiency. Cross-sectional and prospective studies in pre-menopausal women have shown DMPA use to be associated with reduced bone density, but bone density increases following discontinuation of the drug. Because fracture rates are low in pre-menopausal women, the principal concern arising from the effects of DMPA on bone is that there may be residual osteopenia in former users such that their post-menopausal fracture risk is increased. The present study addresses this question. DESIGN: Cross-sectional study of bone density in post-menopausal former users of DPMA and controls. SUBJECTS: Three hundred and forty-six normal post-menopausal women, of whom 34 had previously used DMPA. The median age at which DMPA use began was 41 years and the median duration of use was 3.0 years. MEASUREMENTS: Bone density was measured in the spine, proximal femur and total body by dual-energy, X-ray absorptiometry. RESULTS: There were no significant differences in bone density at any site between the women who had previously used DMPA and the others in the cohort. However, in those who had used DMPA for > 2 years there was a trend towards bone densities being lower in the former users, the differences from non-users being 1.6% in the lumbar spine (P = 0.6), 3.1% in the femoral neck (P = 0.4) and 0.5% in the total body (P = 0.8). There was no correlation between bone densities and the duration of DMPA use, the age at discontinuation of DMPA, or the time between DMPA discontinuation and the menopause. CONCLUSIONS: Any residual effects of depot medroxyprogesterone acetate use on post-menopausal bone density are small and therefore unlikely to have a substantial impact on fracture risk in the post-menopausal years.

PIP: The possibility that use of depot medroxyprogesterone acetate (DMPA) has residual effects on postmenopausal bone mineral density was assessed in a cross-sectional study of 346 postmenopausal former users of DMPA and controls from Auckland, New Zealand. 34 women (10%) reported past use of DMPA, for a median duration of 3 years, starting at a median age of 41 years. Dual-energy, x-ray absorptiometry failed to reveal significant differences between past users of DMPA and never-users in bone density in the spine, proximal femur, or total body. However, in women who had used DMPA for more than 2 years, there was a nonsignificant trend toward lower bone densities in former users compared with never-users. The difference between mean measurements was 1.6% in the lumbar spine (p = 0.6), 3.1% in the femoral neck (p = 0.4), and 0.5% in the total body (p = 0.8). There was no correlation between bone densities and the duration of DMPA use, age at discontinuation of DMPA use, or the time between DMPA discontinuation and menopause. These findings suggest that any residual effects of DMPA use on postmenopausal bone density are likely to be small and without a substantial impact on fracture risk.

Frequent urination and Depo-Provera. Ask the experts.

PIP: This "Ask the Experts" column addresses two concerns related to use of Depo-Provera. The first question relates to the clinical significance of frequent urination. Two of the three experts assert that frequent urination in a Depo-Provera user is unlikely to be related to method use; urinary tract infection and diabetes are more probable causes. The third notes that hypoestrogenicity could be a factor and suggests examination of the vagina for atrophy, which could cause the tissue around the urethra to become atrophic. The second question addresses techniques for confirming menopause in Depo-Provera users. The experts concur that measurement of follicle-stimulating hormone in perimenopausal Depo-Provera users lacks predictive value. Recommended, instead, is continuation of Depo-Provera with supplemental estrogen until the woman is in her mid-50s. At that time, conventional hormone replacement therapy can be initiated.^ieng

Bone mineral density in long-term depot medroxyprogesterone acetate acceptors.

The study of bone density in long-term DMPA users is reported. The aims were to study and compare bone density in long-term DMPA users with intrauterine device (IUD) users. Fifty current users of DMPA with a minimum 36 months previous use were compared to 50 current IUD users as control. The bone mineral density was measured by dual energy x-ray absorptiometry (DEXA) at the non-dominant distal and ultradistal forearm. Serum estradiol was measured by microparticle enzyme immunoassay technique in both groups. Age, income, weight, height, BMI, and parity of both groups were matched. The mean bone mineral density of distal forearm in DMPA and IUD users was 0.48 +/- 0.05 g/cm2 in both groups. The mean bone mineral density of ultradistal forearm was 0.38 +/- 0.06 g/cm2 in DMPA users and 0.4 +/- 0.05 g/cm2 in IUD users. No differences in mean bone mineral density of distal and ultradistal forearm between DMPA and IUD users was demonstrated (95% CI -0.02, 0.02 and -0.04, 0.001, respectively). However, the serum estradiol levels were significantly different between DMPA and IUD users (95% CI -122, -68.1). From this study, it is suggested that long-term DMPA use should not have any adverse effect on bone density even if it reduces serum estradiol.

PIP: To assess the long-term effect of depot medroxyprogesterone acetate (DMPA) on bone mineral density, 50 current DMPA users with a minimum of 36 months (mean, 59.14 months) of continuous use recruited from a family planning clinic in Bangkok, Thailand, were compared with 50 current IUD users. Bone mineral density was measured by dual energy x-ray absorptiometry at the non-dominant distal and ultradistal forearm. Cases and controls were matched for age, income, weight, height, body mass index, and parity. Women with conditions known to affect bone density (e.g., smoking, alcohol consumption, metabolic bone disease) were excluded from both groups. The mean bone mineral density of distal forearm was 0.48 +or- 0.05 g/sq. cm in both groups, while the mean bone mineral density of ultradistal forearm was 0.38 +or- 0.06 g/sq. cm in DMPA users and 0.4 +or- 0.05 g/sq. cm in IUD users, a non-significant difference. However, serum estradiol levels measured within 5 days after cessation of menstruation were significantly reduced in DMPA users (52.67 +or- 25.1 pg/mL) compared to controls (147.51 +or- 91.9 pg/mL). These findings indicate that, even though DMPA induces estrogen deficiency, there seems to be no adverse effect on bone density.

Depot medroxyprogesterone. Management of side-effects commonly associated with its contraceptive use.

Depot medroxyprogesterone acetate is one of the most popular, effective methods of contraception used in the United States. Many women experience unpleasant side effects from this method, including episodic vaginal bleeding, hair loss, depression, and weight gain. This Clinical Practice Exchange describes the treatment strategies for these side-effects used by nurse-midwives from a variety of settings and locales. Contraceptive use can be more acceptable for many women if they are better able to cope with unpleasant side effects of the method. This Clinical Practice Exchange provides knowledge to enhance client coping.

PIP: In this clinical practice exchange, nurse-midwives in a variety of settings and US regions describe their treatment strategies for addressing the side effects associated with depot medroxyprogesterone acetate (DMPA). Although DMPA is a safe, effective, long-acting method of hormonal contraception, this injectable has been linked with side effects such as weight gain, menstrual changes, headache, dizziness, acne, abdominal bloating, breast swelling, depression, reduced libido, and alopecia. Approximately one-third of DMPA acceptors discontinue use by the end of the first year and half discontinue by the end of the second year, primarily because of these side effects. Nurse-midwives report that adolescents who are unable to take the pill consistently and breast-feeding women are ideal candidates for DMPA use. Constant vaginal bleeding, the most troublesome side effect, can be treated through use of ibuprofen, oral estrogen, or oral DMPA. Potential or actual weight gain can be averted through life-style changes such as reduced dietary fats and increased exercise. Unanticipated pregnancies can be avoided by administering the initial DMPA injection within 5 days after the onset of menses. Pre-acceptance anticipatory counseling, along with regular support and encouragement, increase user satisfaction with DMPA.

Depot medroxyprogesterone acetate pioneers. A retrospective study at a North Carolina Health Department.

This article examines the characteristics of the first group of depot medroxyprogesterone acetate (DMPA) acceptors after US Food and Drug Administration (FDA) approval of the method and evaluates their continuation rates and factors associated with discontinuation. This was a population based retrospective study based on 12 months of clinic data for 510 women who began using DMPA in 1993 at a large county health department. Cumulative 12 month life table rates were calculated for the entire group and were then stratified by selected characteristics. The 4, 8, and 12 month continuation rates were 67%, 46%, and 35%, respectively. More than half of these women discontinued because of bleeding and nonbleeding side effects (25% and 28%, respectively). Almost 20% of these women were considered discontinuers because they waited longer than 16 weeks to return for an injection. As measured in this study, continuation rates for this first group of DMPA acceptors were low. The next step is to determine if the characteristics and patterns of use of these "pioneer" acceptors are representative of more recent acceptors, and if lessons learned from this group will lead to higher continuation rates.

PIP: Depo-Provera was approved for general contraceptive use in the US in October 1992. This retrospective study examined the records of the first 510 women who initiated Depo-Provera use at a North Carolina county health department in 1993. The mean age of Depo-Provera users in this series was 23.5 years; 80% were unmarried. The mean number of living children was 1.3. At the time of injection, an appointment was set for a second injection 12 weeks later. Women were considered as continuers as long as they received an injection within 16 weeks of the last injection--the maximum duration of effectiveness. A total of 181 acceptors (36%) continued Depo-Provera use for 12 months, with an average interval between injections of 13 weeks. The 4-month and 8-month continuation rates were 67% and 46%, respectively. Of the 227 discontinuations, 64 were due to non-bleeding-related side effects such as weight gain, headache, and hair loss and 56 were because of bleeding problems. An additional 39 discontinuations were by default, i.e., acceptors waited more than 16 weeks for repeat injection and were refused. Another 102 women (20%) were lost to follow-up. If it is assumed that women lost to follow-up continued at the same rate as other women, the 12-month continuation rate rises. Discontinuation rates were significantly lower among only two sociodemographic groups: women covered by Medicaid for either all or none of the injections and women who reported bleeding side effects at their last injection. The provision of estrogen therapy to Depo-Provera users who experience irregular bleeding could increase compliance with this new method.

[Our regions evaluate the program. Contraception by injectable progestin, Depo Provera: opportunity, continuity and analyses of the situation in central west Tunisia]. / Nos regions evaluent le programme. La contraception par progestatif injectable, Depo-Provera: opportunite, continuite et analyses de la situation au Centre-Ouest (Tunisie).

PIP: Injectable progestin contraception is controversial. It is disliked by gynecologists, who tend to see only the users with complaints, but is sought by many women for its simplicity of use, noninvasiveness, and independence of coitus. Because it is associated with no major risks, the method should be reevaluated. Records of 3174 users of Depo-Provera in the Center West region of Tunisia were examined for 1995 and 1996. The users' average age was 31.5 years and the average parity was 3-4. The continuation rate, a good indicator of acceptability, was low: only 48% returned for a second injection, 24% for a third, and 13% for a fourth. Only 1% completed 2 years of use. The causes of discontinuation were amenorrhea (10%), bleeding problems (6%), desire for pregnancy (2%), and change of method (7%). 75% of users were lost to follow-up, and it is likely that a significant number sought specialized care for menstrual problems. It is concluded that Depo-Provera still has a place in family planning, but it should be encouraged more for short-term or temporary use than as a long-term solution to contraception problems.^ieng

Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long-acting Systemic Agents for Fertility Regulation.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.

PIP: The findings of a multicenter clinical trial challenge the practice of estrogen treatment of the prolonged or irregular vaginal bleeding associated with depot medroxyprogesterone acetate (DMPA) contraceptive use. Included in the study were 1035 DMPA users (mean age, 27 years) from Alexandria, Egypt; Bangkok, Thailand; Chiang Mai, Thailand; Jakarta, Indonesia; Karachi, Pakistan; and Manila, Philippines. 456 (44%) of these women experienced a bleeding episode lasting more than 7 days during their first 6 months of DMPA use. Of these, only 278 (61%) requested treatment. These 278 women were randomly allocated to receive 50 mcg of ethinyl estradiol (n = 90), 2.5 mg of estrone sulfate (n = 91), or placebo (n = 97) daily for 14 days. The treatment stopped the bleeding episode for 93% of women in the ethinyl estradiol group, 76% of those in the estrone sulfate group, and 74% of women receiving a placebo. The ethinyl estradiol advantage was marginal, however. On average, women treated with ethinyl estradiol had their bleeding episode shortened by 1 bleeding day and 3 spotting days. Immediately after treatment, women given ethinyl estradiol had less bleeding and spotting days than their counterparts in the 2 other groups, but demonstrated a more unpredictable pattern, including a greater range of lengths of bleeding/spotting-free intervals. Three months after treatment, there were no differences between the 3 groups in vaginal bleeding patterns.

Use of depo-provera in teens.

Currently, depot-medroxyprogesterone acetate is the only contraceptive injection available in the United States. Its use was approved by the U.S. Food and Drug Administration in October 1992. This article describes the mechanisms of action, advantages, disadvantages, and contraindications of this very effective contraceptive agent. In addition, the initial workup, the treatment, and the follow-up of the teen receiving depot-medroxyprogesterone acetate are presented.

PIP: US teenagers have had access to the injectable contraceptive depot medroxyprogesterone acetate (DMPA; Depo-Provera) since the US Food and Drug Administration approved it in 1992. DMPA suppresses follicle stimulating hormone and luteinizing hormone (LH) levels, which in turn prevents the LH surge and thus inhibits ovulation. It also causes a thick cervical mucus (reducing sperm penetration). Since DMPA also changes tubal mobility and creates shallow and atrophic endometrium, implantation is prevented. DMPA must be administered every 3 months to be effective. Its first-year failure rate is 0.3%, which is lower than that of oral contraceptives (3%). Advantages of DMPA are that it: allows for privacy; improves compliance (since action is required every 3 months rather than every day); has no estrogen-related complications (e.g., thrombophlebitis); is effective; is safe for breast feeding teenagers; reduces seizure frequency in teenagers with epilepsy; has a favorable effect on sickle cell disease or coagulopathy; reduces menstrual flow, thus preventing iron-deficiency anemia; reduces menstrual pain and pre-menstrual symptoms; and decreases risk of pelvic inflammatory disease. The leading disadvantages are menstrual irregularities and spotting. Some other possible disadvantages include weight gain (most common reason for discontinuation), delayed return of fertility, headaches, acne, and nervousness. Health providers must perform a complete history of teenagers requesting DMPA. They should determine the presence or absence of absolute and relative contraindications to DMPA. Absolute contraindications are known or suspected pregnancy, undiagnosed or abnormal vaginal bleeding, known or suspected history of breast cancer, acute liver disease or jaundice, thromboembolism, and sensitivity to DMPA. DMPA is administered intramuscularly at a concentration of 150 mg/ml. Health providers need to use a frank, nonjudgmental, empathic, and unhurried approach to facilitate a trusting relationship and rapport with teenagers. Advanced counseling on the pros and cons of DMPA, how DMPA works, and DMPA's inability to protect against sexually transmitted diseases is essential.

Comparative phase III clinical trial of two injectable contraceptive preparations, depot-medroxyprogesterone acetate and Cyclofem, in Vietnamese women.

A multicenter clinical trial was conducted in Viet Nam, comparing two injectable contraceptive preparations: the three-monthly injectable depot-medroxyprogesterone acetate (DMPA) and the once-a-month injectable Cyclofem. A total of 600 volunteers were randomized to the two treatment groups and followed for one year. No pregnancy occurred during the trial. Approximately one quarter of the women in each group discontinued early from the trial. In the DMPA group, this was mostly because of amenorrhea and vaginal bleeding irregularities. In the Cyclofem group, an equal number discontinued because of menstrual problems and personal reasons. These personal reasons are probably related to the inconvenience of having to return to the clinic for injection on a monthly basis. Thus, Vietnamese women experience less side effects with Cyclofem than with DMPA, and once Cyclofem is made more widely available and is more accessible, it may better meet their needs than does DMPA.

Early experience with the contraceptive use of depot medroxyprogesterone acetate in an inner-city clinic population.

There are few data on the experience of American women with the injectable depot medroxyprogesterone acetate (DMPA) since its recent approval by the Food and Drug Administration for contraceptive use in the United States. An exploratory study was conducted using chart reviews and telephone interviews of 261 women who initiated DMPA use between December 1992 and June 1994 at either a hospital-based (48%) or community-based (49%) clinic in New York City. Most DMPA users were single (70%), had had at least one birth (88%), had had at least one abortion (67%) and had ever practiced contraception (75% of those with available data). Life-table DMPA continuation rates were 63% at six months and 42% at 12 months and were not affected by the users' age, marital status, pregnancy history, clinic site or proximity of residence to the clinic. Among adults, the risk of DMPA discontinuation was highest during the three-month period following the second injection, while among adolescents, this risk increased throughout the duration of use. The most commonly reported reasons for method discontinuation were side effects, primarily menstrual irregularities (30%) and weight gain (24%).

PIP: An exploratory study of 261 US women who initiated use of depot medroxyprogesterone acetate (DMPA) between December 1992 and June 1994 at a hospital- or community-based clinic in New York City highlighted the importance of side effects to method discontinuation. The mean age of DMPA users was 25 years; 70% were unmarried and 84% were Medicaid recipients. At the time of first injection, 58% were using no contraceptive method. At telephone interview, the average time since first injection was 8.6 months. The continuation rate was 81% at 3 months, 63% at 6 months, 52% at 9 months, and 42% at 12 months. When these rates were adjusted to assume that the 37 women who were not locatable for follow-up had discontinued, they became 74%, 53%, 39%, and 30%, respectively. There was no variation in discontinuation rates on the basis of age, parity, marital status, insurance status, number of pregnancies or abortions, postpartum status, or residence. Among the 96 discontinuers for whom data were available, the most frequently cited reasons were abnormal bleeding (30%), weight gain (24%), and nausea (12%). The percentage of women with amenorrhea was 34% at 3 months, 43% at 6 months, 66% at 9 months, and 60% at 12 months. Among adults, the risk of discontinuation was highest in the 3 months after the second injection; in contrast, the risk of discontinuation among adolescents increased steadily during the first year of use. Given the strong association between DMPA side effects and discontinuation, clinic staff are urged to pursue interventions such as estrogen therapy for amenorrhea and nutrition and exercise counseling for weight gain.

Counseling issues and management of side effects for women using depot medroxyprogesterone acetate contraception.

Patients satisfaction is crucial to maximizing long-term utilization and efficacy of any contraceptive method. Satisfaction is enhanced when appropriate preutilization counseling is offered and when side effects are successfully managed. This article provides a conceptual model for patient counseling, highlights the significant points that should be included in counseling patients about depot medroxyprogesterone acetate (DMPA) and offers clinical suggestions to help evaluate and treat the more common side effects associated with DMPA use.

PIP: Because no contraceptive agent is perfect, patients must weigh the benefits and risks of the contraceptive method they decide to initiate and continue. Individual decision making and provider-client communication interact in complex ways to determine contraceptive behavior. Use of the contraceptive injectable depot medroxyprogesterone acetate (DMPA) should be preceded by counseling which individualizes its risks and benefits, answers all questions (asked and unasked), and develops a longterm plan to minimize side effects. Counseling should cover the contraceptive and noncontraceptive benefits of DMPA; specific side effects such as bleeding changes, weight changes, and fertility changes; the mechanisms of action; and ways to avoid acquiring sexually transmitted diseases. When evaluating and managing side effects, a differential diagnosis independent of DMPA must be considered first (especially for postcoital bleeding and headache). A pregnancy test should be offered in the first month of amenorrhea, after which no treatment is necessary. Ovulation resumption after use may be spontaneous or may be induced with menotropin therapy. Spotting and breakthrough bleeding may be handled by counseling or by a short course of high-dosage ibuprofen or of low-dose estrogen supplementation. Counseling may help women manage weight gain through caloric reduction and an increase in exercise. Acne which occurs soon after adoption of the method may be managed pharmacologically. Increased intake of dietary fiber and fluids may ameliorate the symptoms of abdominal bloating, and temporary nausea can be treated with antacids. Recent research has shown that depression does not increase with DMPA use, although the contraceptive is sometimes implicated in mood changes. Breast tenderness decreases with prolonged DMPA usage and can be managed with proper support garments and a reduction in other causative agents such as caffeine. Women who experience an increase in varicose veins should wear support hose and elevate their legs when possible. Women with symptoms of hypoestrogenic side effects should undergo a serum estradiol level test and appropriate replacement therapy. DMPA can be used immediately postpartum even in breast-feeding women. Women with amenorrhea should be tested for pregnancy before initiating DMPA or reinitiating use at an interval longer than 11-13 weeks. No adverse side effects have been found if pregnancy does occur.