The timing of norplant insertion and postpartum depression in teenagers.

BACKGROUND: This study tested the hypothesis that teenagers who have Norplant inserted during the puerperium report more depressive symptoms during the first postpartum year than their peers who do not receive Norplant. METHODS: We studied the prevalence of depressive symptoms in a group of 212 mothers aged 19 years less, in relation to the timing of Norplant insertion. The participants were divided into 3 groups: 100 (47%) had Norplant inserted during the puerperium (early Norplant users); 72 (34%) had Norplant inserted during the next 10 months (late Norplant users); and 40 (19%) used other contraceptives (40% oral contraceptives; 17% condoms; 43% nothing). Depressive symptoms were measured with the Center for Epidemiologic Studies - Depression Scale. Postpartum depression was defined as a scale score >/=16, 6-12 months after Norplant insertion or delivery. Variables examined as potential confounders were identified a priori from a review of the literature and controlled for in analysis of variance. RESULTS: At delivery, members of the 3 contraceptive groups did not differ significantly with regard to age, race, parity, educational, marital, or socioeconomic status. Late Norplant users were, however, more apt to have new boyfriends (p =. 03), to rate the support they received from the baby's father as poor (p =.004), and experience depression prior to Norplant insertion (p =.02). Contrary to the study hypothesis, late rather than early Norplant insertion was associated with postpartum depression. Multivariate analyses identified 3 independent predictors of the severity of depressive symptoms at follow-up (depression prior to Norplant insertion, a new boyfriend at delivery, and late Norplant insertion); R(2) = 41.3%. CONCLUSIONS: Contrary to the study hypothesis, puerperal Norplant insertion did not exacerbate postpartum depression. Delaying Norplant insertion may increase the risk of depression during the first postpartum year, particularly in teenagers with other psychosocial risk factors.

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.

The effect of mefenamic acid on controlling irregular uterine bleeding secondary to Norplant use.

The aim of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding secondary to Norplant use. A total of 67 Norplant users attending the Family Planning Clinic of Chulalongkorn Hospital all had irregular bleeding. These women were randomly allocated into two groups. A total 34 users received mefenamic acid, 500 mg twice a day for 5 days, and placebos were given to the other 33 in the same manner. The total days of bleeding and spotting and the percentage of women in whom bleeding was stopped were analyzed in weeks 1 and 4. The percentage of subjects in whom bleeding was stopped during week 1 after initial treatment was significantly higher in the mefenamic acid group than the placebo group (76%, 27%; p < 0.001). In the follow-up period (4 weeks after initial treatment), a bleeding-free interval of > 20 days was found in 68% of the subjects treated with mefenamic acid and 33% treated with the placebo; the mean number of bleeding/spotting days was lower with mefenamic acid treatment (11.6 and 17.2 days; p < 0.05). The difference was statistically significant. It is concluded that mefenamic acid was more effective than placebo in short-term control of irregular bleeding and spotting associated with Norplant use.

PIP: This double-blind, placebo controlled study evaluates the effect of mefenamic acid and placebo on controlling irregular uterine bleeding secondary to Norplant use. A total of 67 Norplant users attending the Family Planning Clinic of Chulalongkorn Hospital who had irregular bleeding were divided into two groups. About 34 users received mefenamic acid, 500 mg twice a day for 5 days; placebos were given to the other 33 in the same manner. The total days of bleeding and spotting and the percentage of women in whom bleeding was stopped were analyzed in weeks 1 and 4. The percentage of subjects in whom bleeding was stopped during week 1 after initial treatment was significantly higher in the mefenamic acid group than the placebo group (76% vs. 27%; p 0.001). In the follow-up period (4 weeks after initial treatment), a bleeding-free interval of 20 days was found in 68% of the subjects treated with mefenamic acid and 33% treated with the placebo; the mean number of bleeding/spotting days was lower with mefenamic acid treatment (11.6 and 17.2 days; p 0.05). The difference was statistically significant. Therefore, mefenamic acid was more effective than placebo in short-term control of irregular bleeding and spotting associated with Norplant use.

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.

Levonorgestrel versus the "Yuzpe" regimen. New choices in emergency contraception.

PIP: A double-blind, randomized controlled trial conducted at 21 centers in 14 countries compared the effectiveness and side effects of the traditional Yuzpe method of emergency contraception (200 mcg of ethinyl estradiol and 1 mg of levonorgestrel divided into 2 equal doses) and levonorgestrel alone (2 doses of 0.75 mg each). 1955 women (979 in the Yuzpe group and 976 in the levonorgestrel group) completed the study. 42 women had subsequent pregnancies, although at least 4 women were pregnant at the time of treatment. The pregnancy rate was 1.1% (95% confidence interval [CI], 0.6-2.0) for the levonorgestrel group and 3.2% (95% CI, 2.2-3.5) for the Yuzpe regimen. The relative risk of pregnancy was 0.36 (95% CI, 0.18-0.70). Levonorgestrel prevented 85% of expected pregnancies while the Yuzpe method prevented only 57%. Efficacy increased when the regimen was initiated within 24 hours and decreased as the time after unprotected intercourse approached 72 hours. Women in the levonorgestrel group reported less nausea, vomiting, dizziness, and fatigue than their counterparts in the Yuzpe group. Overall, 57% of women started bleeding within 3 days of their expected menses and the mean duration of menses of 4.7 days in both groups. Results of this study support use of levonorgestrel alone as an alternative for emergency contraception.^ieng

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.

Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study.

BACKGROUND: We have reported previously that, compared with use of second-generation oral contraceptives, the use of third-generation oral contraceptives is associated with increased resistance to the anticoagulant action of activated protein C (APC). Owing to the cross-sectional design of that study, these observations may have been subject to unknown bias or uncontrolled effects of the menstrual cycle. We aimed to overcome these sources of bias by doing a cycle-controlled randomised cross-over trial. METHODS: The response to APC in plasma was assessed in 33 women who received two consecutive cycles of a second-generation oral contraceptive (150 microg levonorgestrel and 30 microg ethinyloestradiol) or a third-generation oral contraceptive (150 microg desogestrel and 30 microg ethinyloestradiol), and who switched preparations after two pill-free cycles. Normalised APC sensitivity ratios were calculated by measurement of the effect of APC on thrombin generation in the plasma of these women and in pooled plasma from 90 controls. FINDINGS: Of the 33 women, five were excluded because not all required plasma samples were available. In the remaining 28 women, the normalised APC sensitivity ratio increased during treatment with both preparations. Compared with levonorgestrel, desogestrel-containing oral-contraceptive treatment caused a highly significant (p<0.0001) additional increase in normalised APC sensitivity ratio (0.51 [95% CI 0.37-0.66]). Normalised APC sensitivity ratios during oral-contraceptive treatment correlated with the values before oral-contraceptive use. INTERPRETATION: Oral-contraceptive treatment diminishes the efficacy with which APC down-regulates in-vitro thrombin formation. This phenomenon, designated as acquired APC resistance, is more pronounced in women using desogestrel-containing oral contraceptives than in women using levonorgestrel-containing preparations. Whether acquired APC resistance induced by oral contraceptives explains the increased risk of venous thromboembolism in oral-contraceptive users remains to be established.

PIP: This cycle-controlled randomized cross-over study examined the effects of a second-generation oral contraceptive (OC) containing levonorgestrel and a third-generation OC containing desogestrel on the anticoagulant action of activated protein C (APC) in the plasma. The response to APC in plasma was assessed in 28 women who received two consecutive cycles of a second-generation OC (150 mcg levonorgestrel and 30 mcg ethinyl estradiol) or a third-generation OC (150 mcg desogestrel and 30 mcg ethinyl estradiol), and who switched preparations after two pill-free cycles. Normalized APC sensitivity ratio was also taken from these women. Results showed that in the 28 women the normalized APC sensitivity ratio increased during treatment with both preparations. Compared with levonorgestrel, desogestrel-containing OC treatment caused a highly significant (p 0.0001) additional increase in normalized APC sensitivity ratio (0.51; 95% CI, 0.37-0.66). In conclusion, OC treatment diminishes the efficacy with which APC down-regulates in-vitro thrombin formation.

Manufacturer moves to settle Norplant claims.

PIP: This article is about the decision made by Wyeth-Ayerst to settle lawsuit claims filed by more than 36,000 American women concerning the use of the Norplant contraceptive implant system. The settlement, estimated at $50 million, would end 5 years of litigation involving Norplant. The plaintiff's lawyers claimed that the company downplayed such side effects as irregular menstrual bleeding, nausea, headaches, and depression. Wyeth-Ayerst Laboratories and parent company American Home Products Corp. have denied any wrongdoing and claimed that the side effects were described in the product label. The agreement to settle the Norplant claims were described as purely a business decision by Wyeth-Ayerst North America president Joseph Mahady.^ieng

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.

Depressive symptoms and Norplant contraceptive implants.

Women enrolled in a multicenter prospective study were evaluated to identify any possible relationship between depressive symptoms and the use of contraceptive implants. Women choosing Norplant implants (n = 910) were evaluated before starting this contraceptive and were reinterviewed at 6 months and 2 years. Women who continued the method had lower depressive symptom scores before initiating Norplant implants than did the women who discontinued the method or who were lost to follow up. Among the continuing Norplant implant users, the mean scores were similar before starting Norplant and at 6 months (7.9 vs 7.7). The strongest overall predictor of the depressive symptom score was relationship satisfaction. At 24 months, the subgroup of continuing users with decreased relationship satisfaction had an increase in depressive symptom score, but those with stable or improved relationships had stable depressive symptom scores. The subjects with the highest (i.e., worst) scores at enrollment demonstrated improved scores during follow-up. These results are reassuring for women who are concerned that Norplant use may adversely affect their mood.

PIP: Although depression is cited in the Norplant contraceptive implant product labeling as a rare side effect, previous evaluations of this association have not included baseline measurement of mood. To assess this association more systematically, the present study followed a cohort of 910 new Norplant acceptors recruited from three urban hospitals in the US (Texas, Pennsylvania, New York) for 24 months. Included in both the initial and follow-up questionnaires were six questions drawn from the Mental Health Inventory on depressive symptoms in the past month. At the end of the study period, 293 women were still using Norplant, 295 had discontinued use, and 138 were lost to follow-up. Women who continued with Norplant for 2 years had significantly lower depression scores at baseline than women who discontinued use or were lost to follow-up. Among continuing Norplant users, mean depressive symptom scores were similar before starting Norplant and after 6 months of use (7.9 and 7.7, respectively). The strongest overall predictor of the depression score was relationship satisfaction. At 24 months, the subgroup of continuing users with decreased relationship satisfaction had an increase in depression score, while those with no change or improved relationships had stable scores. The mean depression score of the quintile of women most depressed at enrollment improved during the study period from 15.4 to 11.0, dispelling concerns that Norplant exacerbates pre-existing depression. Only 4.4% of discontinuers cited mood changes as a reason for terminating Norplant use and there were no cases of psychiatric hospitalization. These findings suggest that concern about possible mood changes is not a reason to withhold Norplant.

Norplant implants and cardiovascular disease.

A 1995 publication on serious adverse events in users of Norplant implants submitted to the Food and Drug Administration's MedWatch Spontaneous Reporting System reported 14 hospitalizations for stroke in Norplant users. This number was higher than expected. This is a report on the association of current use of Norplant implants with stroke and myocardial infarction (MI) based on a pooled analysis of data from two population-based, case-control studies conducted in the US. All data collection for these two studies occurred after approval of Norplant implants for marketing in the US in December 1990. The methods of the individual studies are detailed in prior publications.

PIP: A 1995 publication submitted to the US Food and Drug Administration's MedWatch Spontaneous Reporting System in 1995 identified 14 hospitalizations for stroke in US Norplant contraceptive implant users. This paper reports the findings of a pooled analysis of data from two large population-based case-control studies conducted in California and Washington. Of the 518 stroke patients and their 1547 healthy controls, only 1 stroke patient, 1 ischemic stroke patient, and 3 controls were current Norplant users. After adjustment for age, the odds ratio (OR) for stroke in current compared with noncurrent users of Norplant was 1.0 (95% confidence interval (CI), 0.1-9.2). In addition, 307 myocardial infarction patients and their 1048 controls were available for analysis. Of these, 1 case and 1 control were current users of Norplant. The age-adjusted OR for myocardial infarction in current compared with noncurrent Norplant users was 3.5 (95% CI, 0.2-56.5). The low prevalence of Norplant use in these studies, combined with the rarity of cardiovascular events in women of reproductive age, limited the statistical power of the pooled analysis to determine whether Norplant use increases, decreases, or has no effect on the risk of cardiovascular disease.

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.

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

PIP: The Norplant contraceptive implant has been registered in 60 countries and used by over 6 million women worldwide. Clinical studies have repeatedly confirmed this method's long-term efficacy and safety when used appropriately. Preliminary findings of the Post-Marketing Surveillance study of Norplant, a 5-year prospective study conducted in 32 family planning clinics in 8 developing countries in 1987-97, indicate an intrauterine pregnancy rate of 0.23/100 woman-years, an ectopic pregnancy rate of 0.03/100 woman-years, and a 67.3% continuation rate at 5 years. No significant excess of malignant neoplastic or cardiovascular disease has been observed. The major side effect is an irregular pattern of uterine bleeding, associated with about 25% of the discontinuations after 5 years of use. The quality of the family planning service is a major determinant of successful Norplant use and the degree of user satisfaction. Informed choice, the quality of follow-up care, easy access to removal services, and provider skills and attitudes are also critical. The signatories to this Consensus Statement (acting as individuals rather than representatives of their organizations) agree that, with the provision of appropriate information to users, Norplant is a good contraceptive choice that should be made available globally in all family planning programs with resources for appropriate training and counseling.

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.

Levonorgestrel contraceptive implants in female patients 14 to 21 years old.

OBJECTIVE: To determine which factors are associated with duration of use of a levonorgestrel implant (Norplant) for contraception in adolescents and young adults. DESIGN: We retrospectively studied 144 young women (14 to 21 years of age) who chose a levonorgestrel contraceptive implant at Mayo Clinic Rochester between April 1990 and December 1993. MATERIAL AND METHODS: The following information was obtained at the time of insertion of the implant and from any follow-up visits: demographics, prior contraceptive experiences, frequency and management of complications, complications noted at removal of the implant, and subsequent contraceptive choice. The duration of use was examined. RESULTS: Of the 144 young women who underwent insertion of a Norplant system, 75 telephoned or made a medical appointment because of implant-related side effects. During the follow-up period, 64 patients had the Norplant system removed. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83 % and for at least 24 months was 63 %. Duration of Norplant use was not found to differ with respect to age, prior contraceptive use, or timing of insertion, but it was significantly shorter among those with a prior pregnancy than in those who had never been pregnant. CONCLUSION: These findings suggest that a group of young women who are likely to continue use of a contraceptive implant (with or without treatment for side effects) are those who have never been pregnant.

PIP: A retrospective study of 144 US women 14-21 years of age who requested and received the Norplant contraceptive implant system at the Mayo Clinic (Rochester, Minnesota) in 1990-93 analyzed the factors associated with duration of method use. Of the 124 women who reported past use of contraception, 94 (76%) had been pregnant at least once. The method most commonly used before Norplant was oral contraception (57%). The reasons for Norplant selection were its convenience (86%) and problems tolerating the pill (14%). Of the 130 Norplant users who either telephoned or made a clinic appointment after insertion, 60% reported side effects such as breakthrough bleeding, headache, and depression or mood swings. 64 women had the implants removed. The median duration of Norplant use was 29 months. The Kaplan-Meier estimate of the probability of the Norplant system remaining in place for at least 12 months was 83% and 63% for at least 24 months. Age, prior contraceptive use, and timing of insertion had no impact on duration of Norplant use. Multivariate analysis indicated that women with at least 1 prior pregnancy had a two-fold increased risk of Norplant removal compared to those who had never been pregnant. Larger studies are needed to identify additional factors associated with long-term use of injectable contraception among young women and to suggest interventions that would improve compliance with routine follow-up.

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.