Injectable Depot Medroxyprogesterone Acetate Research Articles

Interval of Injections of Intramuscular Depot Medroxyprogesterone Acetate in the Long-Term Treatment of Endometriosis-Associated Pain: A Randomized Comparative Trial

Aim: To determine the optimal interval of injections of intramuscular depot medroxyprogesterone acetate 150 mg in the long-term treatment of endometriosis-associated pain. Method: 112 patients with symptomatic endometriosis were randomized to receive either injections every month for 6 months, then every 3 months for a total of 15 months or injections every 3 months for 15 months. The primary outcome measure was patients’ satisfaction. Result: At months 3, 6, 9, 12 and 15 of the treatment phase, there was no statistically significant difference of percentages of patients with satisfaction between the two regimens (85.7 vs. 76.8%, 76.8 vs. 73.2%, 66.1 vs. 58.9%, 60.7 vs. 55.4%, 60.7 vs. 55.4%, respectively). Conclusion: The optimal interval of injections of depot medroxyprogesterone acetate 150 mg is every 3 months.

Rates of Follow-up and Repeat Pregnancy in the 12 Months After First-Trimester Induced Abortion

To estimate the proportion of women who returned for a routine follow-up visit after elective abortion and to identify factors associated with repeat pregnancy in the subsequent year. We performed a historical cohort study of 865 women who underwent first-trimester surgical abortion at a hospital-based family planning clinic between March 2003 and February 2004. We collected demographic and clinical data from procedure notes and a computerized hospital patient database. We used univariable and multivariable logistic regression to analyze associations between patient characteristics and repeat pregnancy within 1 year. There were a total of 865 women in our cohort. Of these, 753 (87%) returned to the medical center for care; 485 women returned on time, 268 women returned late, and 112 had no further visit. There were 161 repeat pregnancies; 87 (17.9%) in the on-time group and 74 (27.6%) in the late group (P<.001). There were 85 repeat abortions; 42 (8.7%) in the on-time group and 43 (16.0%) in the late group (P<.001). Multivariable analysis demonstrated that on-time follow-up was associated with a reduction in repeat pregnancy (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37-0.77) and repeat abortion (OR 0.53, 95% CI 0.33-0.86). A total of 130 women received injectable depot medroxyprogesterone acetate (DMPA) at the time of abortion. The rates of repeat pregnancy and abortion in these women were 13.7% and 6.2%, respectively. Women who received DMPA had a decrease in rates of repeat pregnancy (OR 0.41, 95% CI 0.23-0.73) and repeat abortion (OR 0.45, 95% CI 0.20-0.99). Timely follow-up and immediate administration of DMPA are associated with a decrease in repeat pregnancy in the 12 months after first-trimester elective abortion.

When to start hormonal contraceptives

“Women beginning hormonal contraception are often told to wait until their next menstrual cycle before starting. This starting day might be the first day or the first 5 to 7 days of their menses, or the Sunday after their menses begin. This variety of options can cause confusion. Delaying contraception until menstruation starts can also affect access for women with irregular menses. For example, clients for family planning in developing countries might be denied contraception if they are not menstruating at the time. The basis for the delay is to avoid the use of a hormonal contraceptive during an undetected pregnancy, but research has not shown an increased risk for the fetus. An alternative is to start hormonal contraceptives right away using some other form of birth control as a back up for the first week. This “immediate-start” or “quick-start” was introduced with combined oral contraceptives and has been expanded to other hormonal methods. But, before our Cochrane review, we didn't know how it compares to conventional start in terms of the effectiveness and acceptability of contraception, or the continued use by women. We examined randomized controlled trials to try to find out. We looked for published and unpublished research and found five trials. Three studies compared immediate versus conventional start of the same contraceptive method. The fourth study tested the injectable depot medroxyprogesterone acetate, often called ‘depo’. It compared an immediate start with using a ‘bridge’ to depo, such as pills, the patch, or a vaginal ring, for 21 days before the first injection. The fifth trial compared two immediate-start methods, the vaginal ring and an oral contraceptive. Four of the trials reported information on the proportion of women who became pregnant. In the ‘depo’ study, women with immediate start had fewer pregnancies than those allocated to the ‘bridge’ method. However, lots of women were lost from this trial, which might have biased its results. In the other studies, a similar number of women got pregnant in both groups, including the largest trial of more than 1700 women. The proportion of women who stopped taking their contraceptive or had side effects was also similar for the immediate and the conventional start groups. Overall, we found little evidence that beginning hormonal contraceptives right away is better or worse than a delayed start. Immediate start appears to be one of several acceptable options for using hormonal contraceptives. More trials of immediate versus conventional start of the same hormonal contraceptive would help to be sure about this. Consistent reporting of bleeding and other side effects would also help with interpretation of the results across trials, and better follow up of the women in the studies is critical, as high losses threaten the validity of the research.” This systematic review is available in full in The Cochrane Library (http://www.thecochranelibrary.com): Lopez LM, Newmann SJ, Grimes DA, Nanda K, Schulz KF. Immediate start of hormonal contraceptives for contraception. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD006260. DOI: 10.1002/14651858.CD006260.pub2.

Contraception and gynaecological care

Hormonal contraception, through suppression of ovarian activity or endometrial proliferation, can be used to treat and prevent a range of gynaecological disorders. There is evidence to support the effectiveness of the levonorgestrel intra-uterine system (LNG-IUS), combined oral contraceptive pill (COC) and progestogen-only injectable depot-medroxyprogesterone acetate for treating heavy menstrual bleeding and dysmenorrhoea. COCs are also an effective treatment for acne and hirsuitism, and may lessen the symptoms of premenstrual syndrome. There is good evidence that COCs can significantly reduce the risk of both ovarian and endometrial cancer. There is also some evidence that COCs may prevent ovarian cysts, endometrial hyperplasia and fibroids. The LNG-IUS may be used as endometrial protection in women using hormone replacement therapy or tamoxifen. This chapter will deal with the evidence for both treatment and prevention of a range of gynaecological disorders of different hormonal contraceptive methods.

Effect of depot-medroxyprogesterone acetate injections on serum immunoglobulins and complements level

Effect of depot-medroxyprogesterone acetate injections on serum immunoglobulins and complements level

Depo-Provera and skeletal health: a survey of Florida obstetrics and gynecologist physicians

Objective In November of 2004, the US Food and Drug Administration (FDA) issued a black box warning regarding skeletal health concerns with depot medroxyprogesterone acetate (DMPA) contraception. This FDA labeling change has the potential to impact how this contraceptive is used. Our goal was to assess the impact of the FDA decision on how Florida obstetrician-gynecologists prescribe DMPA. Methods A survey was conducted with questions and case scenarios regarding the use of DMPA before and after the black box warning. The survey was sent to all members of the Florida Obstetric and Gynecologic Society. Results Four hundred twenty-five surveys were mailed and 149 were returned — a 35% return rate. Forty-six percent of physicians surveyed indicated that they place a time limit on DMPA use, and 66% stated that this limit was based on the FDA black box warning. Sixty-five percent of respondents ordered bone mineral density (BMD) testing solely due to the use of DMPA, with 58% indicating that this decision was based on the black box warning. Eight (5.4%) of the respondents indicated they selectively prescribe bisphosphonates for patients based solely on the use of DMPA, while 33% of respondents state that they use estrogen supplementation. There was a trend towards fewer DMPA injections per week after the black box warning as compared to before; however, this trend was not statistically significant (p<.125). Conclusion Respondents may be writing fewer prescriptions for DMPA, are likely to institute a time limit on said prescription and are likely to order BMD testing, using the black box warning as justification. Continued education is necessary to prevent inappropriate restrictions on DMPA use and the performance and/or prescription of inappropriate tests and medications.

Effect of Depot Medroxyprogesterone Acetate on Glucose Tolerance in Generalized Lipodystrophy

Lipodystrophy is a rare condition causing severe insulin resistance and frank diabetes. Depot medroxyprogesterone acetate (DMPA), a commonly used contraceptive, may worsen glucose tolerance in diabetics and those with lipodystrophy. A young woman with generalized lipodystrophy, who previously required greater than 1,000 units of insulin daily, had a normal hemoglobin A1c on leptin and metformin only. After an injection of DMPA, she developed severe hyperglycemia. Her levels returned to near normal only with extremely high doses of insulin (up to 1,700 units/d) and increased doses of leptin and metformin. Progestin-only contraceptives may detrimentally affect glucose tolerance, particularly in patients with lipodystrophy, a cause of severe insulin resistance and leptin deficiency. One DMPA injection appeared to profoundly alter glucose metabolism in this patient with frank diabetes resulting from lipodystrophy. The effect of progestin-only contraceptives on glucose tolerance should be monitored closely in any diabetic patient.

Progress and prospects in male hormonal contraception

Testosterone functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary. Low concentrations of these hormones deprive the testes of the signals required for spermatogenesis and results in markedly decreased sperm concentrations and effective contraception in a majority of men. Male hormonal contraception is well tolerated and acceptable to most men. Unfortunately, testosterone-alone regimens fail to completely suppress spermatogenesis in all men, meaning that in some the potential for fertility remains. Because of this, novel combinations of testosterone and progestins, which synergistically suppress gonadotropins, have been studied. Two recently published testosterone/progestin trials are particularly noteworthy. In the first, a long-acting injectable testosterone ester, testosterone decanoate, was combined with etonogestrel implants and resulted in 80-90% of subjects achieving a fewer than 1 million sperm per milliliter. In the second, a daily testosterone gel was combined with 3-monthly injections of depot medroxyprogesterone acetate producing similar results. Testosterone-based hormone combinations are able to reversibly suppress human spermatogenesis; however, a uniformly effective regimen has remained elusive. Nevertheless, improvements, such as the use of injectable testosterone undecanoate, may lead to a safe, reversible and effective male contraceptive.

The cost-effectiveness of long-acting reversible contraceptive methods in the UK: analysis based on a decision-analytic model developed for a National Institute for Health and Clinical Excellence (NICE) clinical practice guideline

Long-acting reversible contraceptive (LARC) methods are highly effective in preventing unintended pregnancies. However, their uptake is low in much of the developed world. This study aimed at assessing the cost-effectiveness of LARC methods from the British National Health Service (NHS) perspective. A decision-analytic model was constructed to estimate the relative cost-effectiveness of the copper intrauterine device (IUD), the levonorgestrel intrauterine system (LNG-IUS), the etonogestrel subdermal implant and the depot medroxyprogesterone acetate injection (DMPA). Comparisons with the combined oral contraceptive pill (COC) and female sterilization were also performed. Effectiveness data were derived from a systematic literature review. Costs were based on UK national sources and expert opinion. LARC methods dominated COC (i.e. they were more effective and less costly). Female sterilization dominated LARC methods beyond 5 years of contraceptive protection. DMPA and LNG-IUS were the least cost-effective LARC methods. The incremental cost-effectiveness ratio of implant (most effective LARC method) versus IUD (cheapest LARC method) was pound13 206 per unintended pregnancy averted for 1 year of use and decreased until implant dominated IUD in 15 years. Discontinuation was a key determinant of the cost-effectiveness of LARC methods. LARC methods are cost-effective from the British NHS perspective. Practices improving user satisfaction and continuation of LARC method use should be identified and promoted.

Undetectable levels of serum FSH immunoactivity and bioactivity in girls with sexual precocity due to ovarian cysts.

Clinical presentation and endocrine investigations in five girls with precocious sexual development due to ovarian cysts are presented. These girls had pubertal oestradiol and suppressed gonadotrophin responsiveness to LHRH stimulation. FSH bioactivity as measured by the rat aromatase assay was undetectable in basal and LHRH-stimulated serum samples but our results cannot exclude the possibility of the presence of a species-specific follicle stimulating factor in these patients. IM injection of depot medroxyprogesterone acetate controlled pubertal development in two children.

Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy

To evaluate the effect of an antiretroviral (ARV) therapy regimen containing zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV) on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA). Open-label, nonrandomized, clinical trial. University hospital clinic. Thirty HIV-infected women; 15 using ARV therapy (AZT, 3TC, and EFV) and 15 non-users of ARV therapy, followed biweekly for 12 weeks. Single injection of DMPA (150 mg IM) for both groups. Pharmacokinetic parameters of DMPA by liquid chromatography with mass spectrometry, and ovulation by serum P. Maximum serum concentrations of DMPA were reached at 14 days after injection. The area under the curve was similar in both groups, as were the minimum concentration, half-life, and clearance. Only 1 woman, not using ARV therapy, ovulated at 11 weeks after DMPA. Pharmacokinetics of DMPA were similar in HIV-infected women, regardless of ARV therapy use, suggesting that triple therapy with AZT, 3TC, and EFV is not likely to interfere with the contraceptive effectiveness of DMPA.

Reproductive cycles and contraception of black lemurs (Eulemur macaco macaco) with depot medroxyprogesterone acetate during the breeding season

Contraception is a critical component of population management for lemurs, but concerns about potential deleterious effects of continuous, long-term treatment with synthetic progestins such as the widely used melengestrol acetate implant led us to evaluate seasonal contraception with injections of depot medroxyprogesterone acetate (Depo-Provera, Upjohn Pharmacia, Kalamazoo, MI) to limit the duration of exposure. We compared two dosage regimens in female black lemurs using vaginal cytology as an indirect measure of ovarian suppression. Our results indicate that both 10 mg/kg body weight at 90-day intervals or 2.5 mg/kg at approximately 30-day intervals can be effective in most females, although one female on the 10-mg dose showed signs of estrus at 53 days. Darkening of pelage during treatment was the primary side effect noted. A more important observation was that contraception can extend the breeding season to as much as 9 months, considerably longer than reported previously, which necessitates extending the period of contraceptive treatment. Zoo Biol 26:289-298, 2007. (c) 2007 Wiley-Liss, Inc.

Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort

Objective To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception. Methods Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year. Results There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study. Conclusions There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.

Why Wait? Initiating Depo Now Contraceptive Injections

Waiting until the onset of menstruation to initiate depot medroxyprogesterone acetate (DMPA) injections might increase the risk for unintended

Initiation and continuation rates seen in 2-year experience with Same Day injections of DMPA

Background Women often need prompt initiation of effective contraception. Quick Start/Same Day Start protocols for combined hormonal contraceptive methods have been extensively studied. Experience with Same Day injections of longer-acting progestins is less well reported. The Same Day injection protocol is comprehensive and includes emergency contraception, backup methods for 7 days and repeat pregnancy testing within 2–3 weeks. Study Design This is a historical cohort study based on review of the charts of all women who received injections of depot medroxyprogesterone acetate (DMPA) at the Women's Health Care Clinic at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center between January 1, 2003, and December 31, 2004. Results The study population included 1056 women who had a total of 3185 DMPA injections. More than 81% of the initial injections were given Same Day — outside the first 5 days of menses. At each reinjection, 14–27% of women were late and also benefited from rapid access to DMPA. Continuation rates were low in both groups but were not lower among those who utilized Same Day injections compared with On Time starters. Six pregnancies were diagnosed, all in the Same Day Start group. Conclusions The introduction of DMPA as a Same Day injection policy is a safe and efficient way of providing women needed effective contraception within 7 days of the office visit.

Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain

To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of endometriosis. Phase 3, multicenter, randomized, evaluator-blinded, comparator-controlled trial. Clinical trial sites in Canada and United States. Two hundred seventy-four women with surgically diagnosed endometriosis. Intramuscular injections of DMPA-SC (104 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow-up. Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight. The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months' follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months' follow-up. No statistically significant differences in median weight changes were observed between groups. Compared with leuprolide, DMPA-SC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.

Steroid receptor expression in vaginal epithelium of healthy fertile women and influences of hormonal contraceptive usage

Background The objective of this study was to evaluate whether long-term usage of hormonal contraceptives modifies the steroid receptor expression in the human vaginal epithelium of healthy young women. Methods In a cross-sectional study, three groups of hormonal contraceptive users [combined oral contraceptives (COCs), levonorgestrel implants (LNG) and depot medroxyprogesterone acetate injections (DMPAs)] were compared to controls. Fifteen subjects (20–34 years) were enrolled to each group. Vaginal biopsies were collected at two occasions from each subject, and serum concentrations of E 2 and progesterone were measured. Monoclonal antibodies directed against progesterone receptors (PRs) and estrogen receptors (ERs) were used in immunohistochemistry on formalin-fixed tissue sections of vaginal mucosa. A program for immunohistomorphometric quantification was devised to estimate frequency of epithelial steroid receptor-expressing cells. Results Progesterone receptor expression was markedly down-regulated and significantly reduced in DMPA users compared to controls, COC and LNG users. In DMPA users, the ER expression was significantly elevated in the first compared to the second sample, and significantly elevated compared to LNG users. Estradiol concentration in serum was significantly reduced in hormonal contraceptive users compared to controls. Conclusions Steroid receptor expression in human vaginal epithelium is altered by long-term use of DMPA compared to controls.

Randomized assignment to copper IUD or depot-medroxyprogesterone acetate: feasibility of enrollment, continuation and disease ascertainment

Objectives We conducted a feasibility study to enroll and follow family planning acceptors who were randomly assigned to use an intrauterine device (IUD) or injectable depot-medroxyprogesterone acetate (DMPA). Methods Centers in Brazil, Guatemala, Egypt and Vietnam aimed to enroll 100 participants per site. Enrolled women were randomly assigned to have inserted a TCu 380A IUD, or to receive injections of 150 mg of DMPA every 3 months, and scheduled for up to 12 months of follow-up. We tested for cervical infection at first and final visits, and examined for signs of pelvic inflammatory disease (PID) at each visit. Results The sites screened 555 women and enrolled 368. Two women (0.5%) had three discomfort signs of PID during follow-up. The prevalence of gonorrhea at each woman's final follow-up visit was 0.5%, and the prevalence of chlamydia at final visit was 5.4%. Sixty-eight percent of women either completed 12 months of observation with their assigned method or were still using their method at the end of the study. Conclusion A larger, definitive clinical trial appears feasible. The majority of women we approached agreed to participate; nearly 400 women were enrolled; two thirds continued to use their assigned method until study closeout; and the STI risk was moderate.

Bone Mineral Density and Depot Medroxyprogesterone Acetate Contraception

Bone Mineral Density and Depot Medroxyprogesterone Acetate Contraception

Same-day administration of depot-medroxyprogesterone acetate injection: a retrospective chart review

A chart review of clients administered depot-medroxyprogesterone acetate (DMPA) injection in September of 2000 was performed to assess implementation of a same-day injection administration protocol irregardless of menstrual cycle day. Women were classified into one of the three categories: (1) routine injection (injection given as specified by the package label), (2) same-day start injection (no injection for more than 6 months, did not meet labeled criteria for administration and received an injection the day of the visit) or (3) same-day restart injection (injection given within 6 months prior to receiving an injection at the visit despite being late for their injection). Of the 228 women receiving an injection, 104 (46%) had a nonroutine same-day injection, meaning almost half of the women receiving a contraceptive injection would have had to return for another visit if this protocol had not been in place. Among these women administered a same-day injection, 23 (22%) were also dispensed emergency contraception. Only 1 of the 104 women was subsequently identified to have become pregnant. Other pregnancies are presented to illustrate the importance of adherence to pregnancy testing at the time of injection and revisit, and the need for backup contraception. Using a same-day injection protocol, women can have increased access to injection contraception, and proper adherence to a protocol can assure few pregnancies.