Acceptance, Adherence, and Side Effects of Depot Medroxyprogesterone Acetate: A Prospective Observational Study.

Introduction In India, one of the world's most populous and swiftly growing countries, it is crucial to prioritize the utilization of safe and effective contraception, as contraceptive strategies play a pivotal role in bolstering community health. It is widely acknowledged that ensuring appropriate timing and spacing of pregnancies is crucial for the well-being of reproductive, maternal, neonatal, child, and adolescent health. Adoption of reversible or spacing contraceptive methods can significantly enhance women's health outcomes by reducing the occurrence of undesired, closely timed, and mistimed pregnancies. Consequently, in response to the pressing need for dependable contraception in India, this study seeks to assess the acceptance, adherence, and side effects of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) among its users. Methods This prospective observational study was done at the State Government Taluk Hospital in the Cuddalore District of Tamil Nadu from July 2022 to October 2022. A total of 40 women of reproductive age who opted for DMPA as their contraceptive method and met the inclusion criteria were recruited through a purposive sampling method. A structured questionnaire was used to collect the data. Results The majority of the participants were women aged 21-25 years (n=14; 35%). The participants were predominantly Hindu (n=39; 97.5%), and 35 (87.5%) had completed higher secondary education. All participants (n=40; 100%) resided in rural areas and the majority were homemakers. A significant proportion of the participants had two children (n=21; 52.5%), and all of them received information on DMPA primarily from health personnel. At the initial point of data collection, three-fourths of them took the first dose (n=13; 32.5%) and only a few took more than three doses (n=3; 7.5%). In the third month, the results showed a drop in DMPA use, which indicates a lower adherence particularly linked to side effects like irregular bleeding (n=15; 37.5%) and amenorrhea (n=9; 22.5%). Furthermore, 35 (87.5%) of the women chose DMPA for birth spacing due to its efficacy and convenience, with few initiating it during postpartum (n=4; 10%) and post-abortal (n=1; 2.5%) periods. The reasons for continuing DMPA use included efficacy (n=20; 50%), discreet usage (n=15; 37.5%), and curiosity (n=13; 32.5%). Half of the participants reported no side effects. The study identified associations between DMPA users and the number of living children and occupational status inferring that DMPA contraception is used for spacing births. Conclusion The results of this study imply that the use and adherence to injectable contraceptive DMPA need to be strengthened among rural women. Thus, the study suggests incorporating information, education, and communication strategies, to enhance awareness among rural women about injectable contraceptives.

Libido-sexual disorders and abandonment of injectable contraceptives among users of the Ivorian Association for Family Well-Being in Korhogo, Côte d'Ivoire.

Introduction: The recent introduction of modern contraceptive methods in resource-limited countries is confronted with the occurrence of undesirable effects that hinder their use in the long term. This study conducted among the users of the Ivorian Association for Family Well-Being in Korhogo describes the libido-sexual problems associated with the discontinuation of injectable contraceptives in former users. The objective of the study was to identify the factors that led to the abandonment of injectable contraceptives among female users of the Ivorian Association for Family Well-Being in Korhogo between 2018 and 2019. Materials and methods: Qualitative data were collected from 15 former users (24-38 years old) of injectable contraceptives duration of 2-3 months. Additional data were collected from five health workers aged 35-60 years. In-depth interviews were conducted to explore the experience with injectable contraceptives and reasons for discontinuation. Following data collection, audio-recorded data were transcribed, translated, and coded using thematic analysis through an inductive approach. Results: Side effects identified as associated with injectable contraceptives include libido-sexual disorders, unusual bleeding, and weight gain. The most common reason for discontinuation were libido-sexual disorders, which impacted the households' intimacy and provoked their abandonment or the change of contraceptive methods among injectable contraceptive users. Conclusion: Adverse events were dominated by libido-sexual disorders, unusual bleeding, and weight gain leading to the abandonment or change of the contraceptive. These results suggest points of intervention for increasing continuation among users. This intervention should include training of health workers to investigate and manage adverse events related to the use of injectable contraceptives and the improvement of communication between health workers and users on adverse events of injectable contraceptive use.

Prevalence and reasons behind use of injectable contraceptive among the women of reproductive age group: A cross-sectional survey in rural areas of Nadia District, West Bengal.

CONTEXT: Estimated 42 million reproductive age group women currently use injectable contraceptive, fourth most prevalent contraceptive worldwide. AIMS: To find out the prevalence, reasons and the associated factors for using injectable contraceptive among the women of reproductive age group. SETTINGS AND DESIGN: A sub-centre-based observational, cross sectional survey was conducted among 212 reproductive age group women living in the rural areas of a district, West Bengal. METHODS AND MATERIAL: A multi-stage cluster random sampling technique was done considering villages as the cluster to get the required sample. Totally, 212 reproductive age group women were chosen from a total of 16 villages, selected by simple random sampling. Information regarding study variables was collected by direct interview of the respondents by visiting individual houses with help of a pre-designed, semi-structured proforma. Strict confidentiality and anonimousity were maintained throughout the study. STATISTICAL ANALYSIS USED: Data were analysed with SPSS 22.0 (licensed). Mean, median, proportion were used for quantitative variables whereas qualitative attributes were presented by proportion. Associations between dependent and independent variables were tested by Chi-square test. RESULTS: The proportion of teenage marriage was unexpectedly high. More than half mothers were unwilling to have babies in future. One-third of study population used injectable contraceptive, ASHA was the main suggestion provider in choosing the method. The major reasons of use were discomfort in previous method and suggestion of service provider. Irregular menstrual problem and easy maintenance was the commonest cause of dissatisfaction and satisfaction, respectively. CONCLUSIONS: Use of injectable contraceptive must be sincerely promoted through social marketing and the front line health workers should motivate the women to use it by providing correct information.

Femiject, a once-a-month combined injectable contraceptive: experience from Pakistan.

OBJECTIVES: The aims of the study were to compare the 12 month continuation rate, level of satisfaction and bleeding patterns of a once-a-month combined injectable contraceptive (CIC; Femiject), a 3 monthly progestogen-only injectable contraceptive (depot medroxyprogesterone acetate [DMPA]) and combined oral contraceptives (COCs). METHODS: A prospective observational study was conducted at Aziz Medical Centre, Karachi, Pakistan. The study comprised 171 married women aged 19-35 years and requesting contraception. Participants were offered injectable contraceptives or COCs and evaluated twice: once at the beginning of the study and again after 12 months, or earlier if they discontinued use. RESULTS: Sixty (35.1%) women chose COCs, 53 (31.0%) chose DMPA and 58 (33.9%) chose the CIC. The continuation rate was higher among CIC users (p = .034). CIC users were more satisfied with their method compared with those who chose COCs or DMPA (63.8% vs 25.0% and 28.3%, respectively). Most CIC users said they were likely or very likely to use the method again (63.8%); only 25.9% said they would not recommend it to a friend. CIC users had, however, more spotting compared with COC users (60.3% vs 3.3%; p ˂ .001). CONCLUSION: As the continuation rate, level of satisfaction and bleeding profile of CIC users was promising, increased uptake should be encouraged. Our study shows that CIC is a good option for women requesting contraception.

Self-administration of injectable contraception: a systematic review and meta-analysis.

INTRODUCTION: Depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) may facilitate self-administration and expand contraceptive access. To inform WHO guidelines on self-care interventions, we conducted a systematic review and meta-analysis comparing self-administration versus provider administration of injectable contraception on outcomes of pregnancy, side effects/adverse events, contraceptive uptake, contraceptive continuation, self-efficacy/empowerment and social harms. METHODS: We searched PubMed, Cumulative Index to Nursing and Allied Health Literature, LILACS and EMBASE in September 2018 for peer-reviewed studies comparing women who received injectable contraception with the option of self-administration with women who received provider-administered injectable contraception on at least one outcome of interest. Risk of bias was assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for non-randomised studies. Meta-analysis was conducted using random-effects models to generate pooled estimates of relative risk (RR). RESULTS: Six studies with 3851 total participants met the inclusion criteria: three RCTs and three controlled cohort studies. All studies examined self-injection of DMPA-SC; comparison groups were either provider-administered DMPA-SC or provider-administered intramuscular DMPA. All studies followed women through 12 months of contraceptive coverage and measured (dis)continuation of injectable contraception. Meta-analysis found higher rates of continuation with self-administration compared with provider administration in three RCTs (RR: 1.27, 95% CI 1.16 to 1.39) and three controlled cohort studies (RR: 1.18, 95% CI 1.10 to 1.26). Four studies reported pregnancies; all showed no difference across study arms. Four studies reported side effects/adverse events; while two controlled cohort studies showed increased injection site reactions with self-administration, no other side effects increased with self-administration. One study found no difference in social harms. No studies reported measuring uptake or self-efficacy/empowerment. CONCLUSION: A growing evidence base suggests that self-administration of DMPA-SC can equal or improve contraceptive continuation rates compared with provider administration. This benefit comes without notable increases in pregnancy or safety concerns. Self-injection of DMPA-SC is a promising approach to increasing contraceptive use.

Quantification of estradiol cypionate in plasma by liquid chromatography coupled with tandem mass spectrometry: Application in a pharmacokinetic study in healthy female volunteers.

The combination of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg is a highly effective, monthly injectable contraceptive. For the first time, this study presents the development and validation of a sensitive method for estradiol cypionate analysis in human plasma by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Aliquots (500 µL) of plasma were extracted with ethyl ether (100%) and derivatized with dansyl chloride. Its separation was performed on a Jones Chromatography Genesis C8 column and the quantification was performed with a mass spectrometer equipped with an electrospray interface operating in negative ion mode. The run time was 6 min and the calibration curve was linear over the range of 0.005-0.15 ng/mL. The method was applied to evaluate the pharmacokinetics of estradiol cypionate in plasma collected up to 1008 h (42 days) after a single intramuscular administration of 25 mg/mL medroxyprogesterone acetate +5 mg/mL estradiol cypionate to healthy female volunteers (n = 12). The estradiol cypionate maximum plasma concentration (Cmax) was 0.14 ± 0.08 ng/mL reached at 16.83 ± 21.07 h and the area under the plasma concentration versus time curve (AUC0-last) was 14.07 ± 6.32 ng.h/mL. Elimination half-life (t½), apparent volume of distribution (Vd/F), apparent clearance (CL/F) and mean residence time (MRT) were 89.65 ± 76.04 h, 28038 ± 9636 L, 49.02 ± 10.62 L/h and 576.05 ± 238.32 h, respectively, showing that the estradiol cypionate release from the administration site was prolonged and there was no drug accumulation.

Hormonal contraception in women with endometriosis: a systematic review.

OBJECTIVE: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence. METHODS: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. RESULTS: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. CONCLUSIONS: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.

Application of behavioral economics principles to reduce injectable contraceptive discontinuation in rural Ethiopia: A stratified-pair, cluster-randomized field trial.

Background: Contraceptive prevalence in Ethiopia jumped from 6% in 2000 to 36% in 2016, mainly due to increased injectable method use. However, discontinuation rates among injectable users were high (38%). Given that the public sector is the major source for injectable contraceptives, John Snow Inc. (JSI) in collaboration with ideas42 worked with Ethiopia's flagship Health Extension Program to apply behavioral design to mitigate discontinuation of injectable contraceptives. Methods: We applied behavioral economics insights to mitigate the discontinuation of injectable contraceptives. This process created an intervention package, consisting of a health worker planning calendar, a client counseling job aid, and client appointment cards. A stratified-pair cluster-randomized field trial tested the effectiveness of the intervention. The study area included two districts from the four regions where JSI was implementing a family planning program. One district from each region was randomly allocated to the intervention arm. Women visiting health posts to use injectable contraceptives were enrolled in the study. Regression methods, adjusted for study design, participants' backgrounds, and contextual factors, estimated the intervention's effect on discontinuation rates. Results: A behavioral design methodology was feasibly implemented in a rural, low-resource setting in Ethiopia. The resultant intervention package was successfully delivered in 19 satellite health posts in four districts. Intervention adherence was high for the appointment cards and counseling job aid, but not for the planning calendar. The injectable discontinuation rate was 10.8 % (95% confidence interval: 2.2, 19.3) points lower in the intervention area compared to the control area during the post-intervention follow-up survey. Conclusion: The use of two tools informed by behavioral economics -the appointment card and counseling job aid-effectively decreased injectable discontinuation even with the presence of other health system bottlenecks. Behavioral economics insights and the behavioral design methodology have the potential to enhance family planning programs in Ethiopia and elsewhere.

The Injectable Contraceptive Medroxyprogesterone Acetate Attenuates Mycobacterium tuberculosis-Specific Host Immunity Through the Glucocorticoid Receptor.

BACKGROUND: The effects of the widely used progestin-only injectable contraceptives, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A), on host susceptibility to Mycobacterium tuberculosis (Mtb) are unknown. METHODS: We recruited human immunodeficiency virus-uninfected females, not taking any contraceptives, from Cape Town, South Africa, to evaluate the effect of MPA, NET-A, and dexamethasone on Mtb containment in monocyte-derived macrophages co-incubated with purified protein derivative (PPD)-driven peripheral blood-derived effector cells. RESULTS: MPA (P < .005) and dexamethasone (P < .01), but not NET-A, significantly attenuated Mtb containment in Mtb-infected macrophages co-cultured with PPD-driven effector cells at physiologically relevant concentrations and in a dose-dependent manner. Antagonizing the glucocorticoid receptor with mifepristone (RU486) abrogated the reduction in Mtb containment. In PPD-stimulated peripheral blood mononuclear cells, MPA and dexamethasone, but not NET-A, upregulated (median [interquartile range]) regulatory T cells (5.3% [3.1%-18.2%]; P < .05), reduced CD4+ T-cell interferon-γ (21% [0.5%-28%]; P < .05) and granzyme B production (12.6% [7%-13.5%]; P < .05), and reduced CD8+ perforin activity (2.2% [0.1%-7%]; P < .05). RU486 reversed regulatory T-cell up-regulation and the inhibitory effect on Th1 and granzyme/perforin-related pathways. CONCLUSIONS: MPA, but not NET-A, subverts mycobacterial containment in vitro and downregulates pathways associated with protective CD8+- and CD4+-related host immunity via the glucocorticoid receptor. These data potentially inform the selection and use of injectable contraceptives in tuberculosis-endemic countries.

Introducing the subcutaneous depot medroxyprogesterone acetate injectable contraceptive via social marketing: lessons learned from Nigeria's private sector.

OBJECTIVES: The subcutaneous depot medroxyprogesterone acetate (DMPA-SC) injectable contraceptive was introduced in South West Nigeria in 2015 through private sector channels. The introduction included community-based distribution and was supported by a social marketing approach. From program monitoring and evaluation, aimed at understanding performance, market reach and other process measures, we identify lessons learned to inform future scale-up efforts. METHODS: We synthesized the findings from a core set of key performance indicators collected through different methods: (1) implementer performance indicators, (2) phone survey of DMPA-SC users (n=541) with a follow-up after 3 months (n=342) and (3) in-depth interviews with 57 providers and 42 users of DMPA-SC. RESULTS: Distribution of DMPA-SC to private providers was concentrated in states with large urban populations. A shift toward focusing on high-volume family planning facilities coincided with a rapid increase in distribution in late 2016. Users reached in the phone survey were generally older and married with children; few were under age 25. Users and providers reported favorable opinions of DMPA-SC. Many users reported choosing DMPA-SC due to recommendations from providers and friends, and the hope of experiencing reduced side effects compared to other methods. While users reported positive experiences interacting with community-based distributors, the delivery model encountered a number of challenges - high turnover, low motivation, lack of an appropriate compensation package and logistical costs - and was ultimately disbanded. CONCLUSIONS: In the DMPA-SC introductory program in Nigeria, distribution was amplified when focused on high-volume contraceptive providers. Although community-based distribution can be one effective service delivery model for reaching underserved populations, more consideration for balancing cost recovery and public health goals through private sector approaches are needed in the context of South West Nigeria. Additional communications and outreach efforts are needed to reach younger, unmarried users with contraceptive services.

Concordance of self-reported hormonal contraceptive use and presence of exogenous hormones in serum among African women.

OBJECTIVES: Studies that rely on self-report to investigate the relationship between hormonal contraceptive use and HIV acquisition and transmission, as well as other health outcomes, could have compromised results due to misreporting. We determined the frequency of misreported hormonal contraceptive use among African women with and at risk for HIV. STUDY DESIGN: We tested 1102 archived serum samples from 664 African women who had participated in prospective HIV prevention studies. Using a novel high-performance liquid chromatography-mass spectrometry assay, we quantified exogenous hormones for injectables (medroxyprogesterone acetate or norethisterone), oral contraceptives (OC) (levonorgestrel or ethinyl estradiol) and implants (levonorgestrel or etonogestrel) and compared them to self-reported use. RESULTS: Among women reporting hormonal contraceptive use, 258/358 (72%) of samples were fully concordant with self-report, as were 642/744 (86%) of samples from women reporting no hormonal contraceptive use. However, 42/253 (17%) of samples from women reporting injectable use, 41/66 (62%) of samples from self-reported OC users and 3/39 (8%) of samples from self-reported implant users had no quantifiable hormones. Among self-reported nonusers, 102/744 (14%) had ≥1 hormone present. Concordance between self-reported method and exogenous hormones did not differ by HIV status. CONCLUSION: Among African women with and at risk for HIV, testing of exogenous hormones revealed agreement with self-reported contraceptive use for most women. However, unexpected exogenous hormones were identified among self-reported hormonal contraceptive users and nonusers, and an important fraction of women reporting hormonal contraceptive use had no hormones detected; absence of oral contraceptive hormones could be due, at least in part, to samples taken during the hormone-free interval. Misreporting of hormonal contraceptive use could lead to biased results in observational studies of the relationship between contraceptive use and health outcomes. IMPLICATIONS: Research studies investigating associations between hormonal contraceptive use and HIV should consider validating self-reported use by objective measures; because both overreporting and underreporting of use occur, potential misclassification based on self-report could lead to biased results in directions that cannot be easily predicted.

Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes.

Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal.

Home-based administration of Sayana® Press: review and assessment of needs in low-resource settings.

A new presentation of the subcutaneous (SC) injectable contraceptive depot medroxyprogesterone acetate (DMPA) increases the possibilities for home and self-administration of this popular contraceptive method. Sayana® Press is DMPA-SC in the prefilled Uniject™ injection system and consists of one dose that provides 3 months of contraceptive protection. Studies indicate that lay caregiver and self-injection of various medications, including other injectable presentations of DMPA-SC, are acceptable and effective. Introduction of Sayana® Press in developing countries could extend injectable contraceptive delivery safely and effectively beyond the clinic and, eventually, into the home, allowing lay caregiver or self-administration. Research needs for low-resource settings include assessing the acceptability and feasibility of self-injection with Sayana® Press. Feasibility studies necessary for implementing a sustainable home-based delivery program include assessment of training, health systems, policies, infrastructure needs and programmatic considerations to optimize women's ability to manage their self-injection schedule.

Human vaginal histology in long-term users of the injectable contraceptive depot-medroxyprogesterone acetate.

OBJECTIVES: Apparently, depot-medroxyprogesterone acetate (DMPA) increases a woman's risk of acquiring HIV. The objective of this study was to test whether the vaginal mucosal thickness and Langerhans cell counts were significantly different in long-term DMPA users compared with women users of an intrauterine device (IUD) who had never used DMPA. STUDY DESIGN: Cross-sectional study. Twenty-three DMPA users were matched with 23 nonusers controlled for age, body mass index (BMI; kg/m²), and duration of contraceptive use. Four groups of women were evaluated according to the duration of DMPA use: >1, <5; ≥5, <10; ≥10, <15 or ≥15 years. Estradiol (E2) levels were compared between the two groups. Histologic sections of vaginal mucosal biopsies were evaluated to measure the mean epithelial thickness and S100 immunostained sections were used to count the number of Langerhans cells/mm. RESULTS: Mean (±S.D.) E2 levels were significantly lower in DMPA users (39.4±26.6 pg/mL) compared with nonusers (102.6±60.3 pg/mL) despite similar ages (42.3±7.4 and 42.4±7.4 years, respectively). Mean (±S.D.) vaginal thickness was 232.6±108.1 and 229.7±112.9 in DMPA users and nonusers, respectively. There were no differences in vaginal thickness or Langerhans cell count/mm between users and nonusers even after controlling for DMPA duration of use. CONCLUSIONS: Vaginal epithelial thinning or Langerhans cell count was not different between long-term DMPA users and copper-IUD users who had never used DMPA. IMPLICATIONS: No differences were found in vaginal epithelial thickness or in Langerhans cell count between long-term users of the injectable contraceptive DMPA and nonusers.