The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant.

BACKGROUND: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). METHODS: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). RESULTS: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1ß, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. CONCLUSIONS: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. CLINICAL TRIALS REGISTRATION: NCT02550067.

Regular Use of Depot Medroxyprogesterone Acetate Causes Thinning of the Superficial Lining and Apical Distribution of Human Immunodeficiency Virus Target Cells in the Human Ectocervix.

BACKGROUND: The hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization. METHODS: Quantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception. RESULTS: Compared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a nonintact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, although fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group. CONCLUSIONS: DMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.

Scale-up of the DMPA-SC in Nigeria: Why policy matters.

BACKGROUND: Injectable contraceptives have contributed substantially to Nigeria's rise in modern family planning methods usage. They are one of the most commonly used and preferred means of contraception among women in the country. Enabling policies are required to assure contraceptive access, security, and use. This study aimed to investigate the policy environment and how it supports or limits Nigeria's introduction and scale-up of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC). METHODS: The design of this mixed-methods study was cross-sectional. Desk reviews of policy papers, key informant interviews, and in-depth interviews were used to obtain information from respondents about the introduction of DMPA-SC in Nigeria and how existing policies influenced its scale-up. Data on DMPA-SC and other injectables were gathered from Nigeria's national electronic logistics management information system. RESULTS: The findings suggest that policies such as task-shifting and task-sharing, cost-free policies, reproductive health policies, and others created an enabling environment for the scale-up of DMPA-SC adoption in Nigeria. The inclusion of DMPA-SC on the essential medicines list and the approved patent medicines list facilitated the scale-up process by ensuring private sector participation, removing economic barriers to access, fostering greater collaboration among health worker cadres, improving intersectoral partnerships, and improving logistics and client access. Despite significant anomalies in some implementing policies, injectable contraceptive consumption data demonstrate a progressive increase in DMPA-SC use during the study period. The results also indicate that policy initiatives have a favorable impact on the use of DMPA-SC throughout the country. CONCLUSION: The existence of policies, the active participation of stakeholders, and the political will of the Nigerian health system's leadership have all aided in the scaling-up of the DMPA-SC. Understanding how to build an enabling policy climate is critical for providing women with family planning options. These lessons from Nigeria emphasize the importance of these levers, which should be considered by teams intending to introduce innovative health products, particularly in developing countries.

"Men can take part": examining men's role in supporting self-injectable contraception in southern Malawi, a qualitative exploration.

BACKGROUND: The male engagement framework for reproductive health, which presents men as family planning users, supportive partners, and agents of change, is being increasingly incorporated into family planning strategies worldwide. We applied this framework to understand the perspectives of and role that men play in supporting the use of self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC). METHODS: We conducted a qualitative analysis using data from a study conducted in southern Malawi to develop and test a counseling message to introduce DMPA-SC and self-injection. We conducted 4 focus group discussions (FGD) with male community leaders and partners of DMPA-SC users, 13 interviews and FGDs with public and private sector family planning providers, and 30 interviews with female clients. We explored all participant groups' perspectives on what could facilitate or prevent women from choosing self-injection, including views on men's attitudes towards DMPA-SC and self-injection. RESULTS: Overall, participants expressed ways that men could be engaged as cooperative users, supportive partners, and agents of change, and felt that this would help build a more supportive environment for DMPA-SC self-injection use. Men held favorable opinions of DMPA-SC self-injection: they felt that it is useful, described ways they could actively and emotionally support their partners in its use, and described their role in normalizing it. CONCLUSIONS: We suggest that DMPA-SC self-injection has the potential to be both a female-controlled and a cooperative method, based on the ability for women to use it autonomously and the option to encourage male partner involvement (only where the woman welcomes this). Shifting the conversation from viewing men as a barrier to men as a resource may allow us to harness the social capital of men and transform traditional power dynamics, therefore establishing more enabling environments to support autonomy and choice for DMPA-SC and self-injection use.

Self-injectable contraception (DMPA-SC) has the potential to expand family planning access. Once users are trained to self-inject, they can obtain multiple units and self-inject every three months privately, without needing to return to a health provider. Considering men's role in supporting self-injection can inform family planning programs' male engagement strategies.We conducted a study in Southern Malawi which included interviews and focus group discussions with male community leaders and partners of DMPA-SC users, family planning providers, and female family planning clients. We applied the male engagement framework to these data to understand the potential roles men can play as cooperative users, supportive partners, and agents of change. We found that men can support their partners in DMPA-SC self-injection use through actively participating in the injection process, providing emotional support and encouragement, and advocating for other men and communities to accept self-injection and family planning use.We acknowledge that encouraging male participation could potentially lead to women's autonomy being restricted, so offer concrete suggestions to create an enabling environment that keeps women's and girls' needs central. For example, we propose that program materials expand their description of DMPA-SC self-injection to include a potentially cooperative option, which may be appropriate for women who want to involve their partners. Further, we suggest that social and behavioral change programs channel men's social capital in order to normalize self-injection. When their traditional role as norm influencers is harnessed, men may encourage their communities to support women's autonomy and choice for DMPA-SC and self-injection use.

Behavioral effects of different contraceptive methods and HIV acquisition: an ancillary study of the ECHO randomized trial.

BACKGROUND: The ECHO trial randomised 7829 women to depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant (1:1:1) and found no clear difference in HIV incidence between these three groups. We have previously hypothesized that oligo-amenorrhoea induced by DMPA-IM may have a protective effect on HIV acquisition. The aim of this ancillary study was to assess the effects of DMPA-IM, the IUD and the LNG implant on menstrual symptoms and sexual behavior and to correlate these with HIV acquisition. METHODS: At the Effective Care Research Unit (ECRU) in South Africa, of 615 women already randomised to DMPA-IM, the copper IUD and the LNG implant (1:1:1) 552 agreed to participate. Participants completed a 28-day symptom and behavior diary following their one-month ECHO trial visit and returning it at their 3-month follow-up visit. HIV acquisition data were retrieved from ECHO trial records. RESULTS: Of 552 women enrolled on the ancillary study, 390 (70.6%) completed their daily diary; 130, 133, and 127 received DMPA-IM, IUD, and LNG implant, respectively. Thirty-three (5.9%) of these women acquired HIV. Women on the progestin-only contraceptives were more likely to experience amenorrhoea, as expected, and were less likely to have intra-menstrual coitus than IUD users (p < 0.001 for DMPA-IM vs IUD and p = 0.002 for implant vs IUD). Overall coital frequency was highest and condom usage lowest among DMPA-IM users. Intra-menstrual coitus correlated positively, and duration of menstruation correlated negatively, with HIV acquisition, although these effects were not statistically significant (p = 0.09 and p = 0.079, respectively). CONCLUSIONS: Findings support the hypothesis that oligo-amenorrhoea and the associated reduced intra-menstrual coitus may mitigate the potential for an increased biological risk of HIV acquisition with DMPA-IM but more evidence is needed. Study registration number PACTR201706001651380.

There have been concerns that the depot-medroxyprogesterone acetate injection (DMPA-IM) may increase the risk of getting HIV infection. However, a large multicenter randomized study, the ECHO trial, recently compared HIV incidence among women randomized to DMPA-IM, the copper intrauterine device (IUD) and the levonorgestrel (LNG) implant and found little difference in HIV risk between these methods. DMPA-IM often causes no or scanty menstruation; we hypothesized that this may have a protective effect on getting HIV, by reducing exposure to HIV during menstrual bleeding.This ancillary study was done among ECHO trial participants at one of the ECHO study sites in South Africa. The aim was to assess the effects of the three different contraceptives on menstrual symptoms and sexual behavior and to correlate these with the risk of getting HIV. The study required women to complete a 28-day daily symptom and behavior diary after their one-month ECHO trial follow-up visit.We found that fewer women had sex during their periods with DMPA-IM and the LNG implant than the copper IUD, probably because no or scanty menstruation is more common with both DMPA-IM and the implant. Although effects were not statistically significant, having sex during periods tended to have a higher risk of getting HIV and longer periods indicated a lower risk of getting HIV.We concluded that sexual behavior related to menstruation may influence HIV acquisition and may partially explain why the ECHO trial found little difference in HIV incidence between the three contraceptives assessed despite observational evidence of higher biological risk with DMPA related to immune suppression.

Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.

BACKGROUND: Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased perinatal morbidity and mortality. The effects of co-administration of efavirenz and rifampicin on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) are unknown. We hypothesized that clearance of medroxyprogesterone acetate (MPA) would increase when given with rifampicin and efavirenz, thus increasing risk of ovulation. METHODS: This pharmacokinetics (PK) study assessed DMPA among HIV/TB coinfected women on an efavirenz-based antiretroviral treatment and rifampicin-based TB treatment. Plasma MPA concentrations and progesterone were measured predose (MPA only) and 2, 4, 6, 8, 10, and 12 weeks after a single DMPA 150 mg intramuscular injection. The primary outcome measure, MPA concentration (<0.1 ng/mL) at week 12, was assessed using exact 95% Clopper-Pearson confidence intervals. MPA PK parameters were calculated using noncompartmental analysis. RESULTS: Among 42 PK-evaluable women from 5 African countries, median age was 32 years and median CD4 was 414 cells/mm3. Five women (11.9%; 95% CI, 4.0-25.6%) had MPA <0.1 ng/mL at week 12; of these, one had MPA <0.1 ng/mL at week 10. The median clearance of MPA was 19 681 L/week compared with 12 118 L/week for historical controls. There were no adverse events related to DMPA, and progesterone concentrations were <1 ng/mL for all women for the study duration. CONCLUSIONS: DMPA, when given with rifampicin and efavirenz, was safe. MPA clearance was higher than in women with HIV not on ART, leading to subtherapeutic concentrations of MPA in 12% of women, suggesting that more frequent dosing might be needed. CLINICAL TRIALS REGISTRATION: NCT02412436.

Depot Medroxyprogesterone Acetate and the Vaginal Microbiome as Modifiers of Tenofovir Diphosphate and Lamivudine Triphosphate Concentrations in the Female Genital Tract of Ugandan Women: Implications for Tenofovir Disoproxil Fumarate/Lamivudine in Preexposure Prophylaxis.

BACKGROUND: Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective preexposure prophylaxis. The disposition of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TC-TP) exposure in the FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of human immunodeficiency virus (HIV) acquisition, but whether they alter TFV-DP or 3TC-TP exposure, and therefore compromise prevention efficacy, is unknown. METHODS: Fifty premenopausal women living with HIV in Kampala, Uganda, and receiving daily tenofovir disoproxil fumarate/lamivudine were recruited. Ectocervical biopsies were obtained for quantification of TFV-DP and 3TC-TP using liquid chromatography-mass spectrometry. 16S ribosomal RNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank-sum was used to test for differences between contraceptive groups. RESULTS: 3TC-TP concentrations were on average 17-fold greater than TFV-DP concentrations in cervical tissues. TFV-DP concentrations in cervical biopsies were 76% greater in DMPA users compared with women using nonhormonal contraception (n = 23 per group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TC-TP concentrations in cervical tissues. CONCLUSIONS: We found that TFV-DP concentrations were significantly greater in DMPA users compared with women using nonhormonal contraception, suggesting that prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTC-TP, 3TC-TP exposure was significantly greater than TFV-DP in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for preexposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT03377608.

Adolescent and covert family planning users' experiences self-injecting contraception in Uganda and Malawi: implications for waste disposal of subcutaneous depot medroxyprogesterone acetate.

BACKGROUND: Self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is poised to increase access to contraception; however, governments are concerned about the waste management of used units. Self-injectors in Malawi and Uganda are currently instructed to store used units in containers and return them to health workers for disposal. However, this may not be feasible in low-resource settings, especially for younger or covert self-injectors. We describe adolescent (15-19 years) and adult (20-49 years) self-injectors' disposal experiences in Uganda and Malawi. When possible, we compare covert and overt users' experiences. METHODS: We conducted cross-sectional qualitative studies in 2019 with 50 self-injectors in Uganda and 60 in Malawi. We purposively selected approximately half adolescents and included those trained by clinic-based providers and community health workers. We conducted semi-structured interviews and thematic data analysis and compared the findings across settings. RESULTS: Just under half of both samples were adolescents, substantially more of whom were covert users in Uganda (68%) than Malawi (~ 10%). Most participants reported being told to store used units in a container and return them to health workers. About two-thirds of Uganda participants had disposed of at least one unit by the interview, most commonly returning them to health workers. Over one-third of Malawi participants had disposed of at least one unit by the interview, slightly more disposed into latrines compared to returning to health workers. Participants in both settings reported compliance with health workers' disposal instructions as a primary reason for their disposal method. One-fifth of Uganda participants, mostly adolescent covert users, and one-quarter in Malawi said they were told they could dispose into latrines, and often did so. The majority in both settings said they would prefer to dispose units in latrines because they worried about needlestick injuries to others and because it was convenient. Some Uganda adolescent covert users felt returning units to health workers was challenging due to privacy concerns. CONCLUSIONS: While most self-injectors disposed of used units as instructed, findings from both studies suggest that returning units to health workers is not preferred and may not be feasible for some adolescent covert users. More convenient disposal solutions should be identified.

Effects of three long-acting reversible contraceptive methods on HIV target cells in the human uterine cervix and peripheral blood.

BACKGROUND: Hormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; however, the biological mechanisms of this risk remain poorly understood. We aimed to investigate the effects of different hormonal contraceptives on the expression of the HIV co-receptors, CXCR4 and CCR5, on female endocervical and peripheral blood T cells. METHODS: A total of 59 HIV-negative women were enrolled, including 15 initiating DMPA, 28 initiating a levonorgestrel-releasing intrauterine device (LNG-IUD) and 16 initiating an etonogestrel (ETG)-delivering vaginal ring. Peripheral blood and endocervical cytobrush specimens were collected at enrollment and 3-4 weeks after contraception initiation to analyze the expression of CXCR4 and CCR5, on CD4+ and CD8+ T cells using flow cytometry. RESULTS: Administration of DMPA increased the percentages of CD4+ and CD8+ T cells expressing CCR5 in the endocervix but not in the peripheral blood. Administration of the LNG-IUD or the ETG vaginal ring did not affect the percentages of T lymphocytes expressing CXCR4 or CCR5 in the female cervix or peripheral blood. CONCLUSIONS: Increase in the percentage of endocervical T cells expressing CCR5 upon DMPA exposure provides a plausible biological explanation for the association between DMPA use and an elevated risk of HIV infection.

Differential expressions of estrogen and progesterone receptors in endometria and cyst walls of ovarian endometrioma from women with endometriosis and their responses to depo-medroxyprogesterone acetate treatment.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) is an injectable progestin contraceptive that provides a highly effective reduction of pelvic pain in women with endometriosis. Despite its wide use to treat pain associated with endometriosis, its precise mechanisms of action remain unclear. The aims of this study were to investigate the differential expressions of estrogen receptors (ERs), and progesterone receptors (PRs) in endometria and ovarian endometrioma cyst walls of women with endometriosis with and without DMPA treatment. METHODS: Endometria and cyst walls of endometrioma were obtained from 25 to 45 year-old women who suffered from endometriosis and had ovarian endometrioma with the size ≥3 cm. The expression levels of ERs and PRs and the numbers of ER- and PR-positive cells before and after treatment with DMPA were evaluated by Western blot, real-time PCR, and immunohistochemistry. RESULTS: The levels of ERα and ERß expression, their corresponding mRNAs, and numbers of ERα- and ERß-immunoreactive cells in stroma and glands of endometria of the DMPA group were significantly decreased when compared with those of the untreated groups (p < 0.05). In contrast, the levels of PRA/B expression and numbers of PRA/B positive cells in stroma and number of PRB positive cells in stroma and endometrial glands were significantly increased in endometria of the DMPA group when compared with those of the untreated groups. However, in cyst wall the expression levels of these proteins, their corresponding mRNAs, and immonoractive cells were low compared to those in endometria, and DMPA-treatment did not cause any significant changes in these parameters. CONCLUSION: These data indicated that DMPA could upregulate the expressions of PRA/B and down-regulate ERα and ERß in endometria but not in cyst walls from women with endometriosis.

Ugandan providers' views on the acceptability of contraceptive self-injection for adolescents: a qualitative study.

BACKGROUND: Self-injection of subcutaneous depot medroxyprogesterone acetate may offer greater discretion and increase access to injectable contraception, particularly for those who face challenges accessing clinic services. In particular, unmarried adolescents often encounter stigma when seeking services, and may also lack the financial means to travel to clinics on the quarterly basis that injectable contraception requires. Whether self-injection is offered to women on a wide scale basis, and to adolescents specifically, will depend in part upon the willingness of providers to train clients of diverse ages and educational backgrounds. This study explores the views of providers with regard to self-injection as an option for women and adolescents in Uganda. METHODS: In-depth qualitative interviews were conducted with family planning providers in Gulu district, to understand their views on injectable self-injection for women, with a specific focus on unmarried adolescents ages 15 to 19 years. The in-depth interviews, which lasted up to 60 min were audio-recorded, translated and transcribed simultaneously, and analyzed using Atlas.ti software to identify key themes and common perspectives. RESULTS: A total of 40 health care providers were interviewed with equal numbers of each type (public, NGO, and private clinics, pharmacies, and community-based health workers). While most providers were receptive to self-injection for adult women, fewer than half were supportive of adolescent self-injection. Their reservations focused on age, marital status and parity concerns around adolescent use of the injectable more broadly, and concerns about the ability of adolescents to self-inject safely. CONCLUSIONS: Self-injection presents an opportunity to reduce the enormous burden on the public sector health system in Uganda, which is particularly compounded by the heavy reliance on injectable contraception requiring quarterly clinic visits. The results of this study reveal a level of cautious support for self-injection among providers when it comes to self-injection by adult women. With respect to adolescent clients, family planning policymakers and program implementers should design, implement, and evaluate self-injection interventions with the needs of adolescent clients uppermost in mind, recognizing that extra attention will likely be needed to reduce provider-imposed restrictions on adolescent access to this injectable delivery modality.

Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices.

Background: Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods: Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results: We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P = .009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions: These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.

The impact of depot medroxyprogesterone acetate on fracture risk: a case-control study from the UK.

There has been concerning about women receiving depot medroxyprogesterone acetate (DMPA) contraception because of the prolonged hypoestrogenemic state regarding the potential negative effects on bone health. This study showed that DMPA exposure is associated with increased fracture risk and that fracture risk increases with longer DMPA exposure. INTRODUCTION: DMPA has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. We performed this large population-based study to assess the association between use of DMPA or combined oral contraceptives and the incident risk of fracture. METHODS: We identified 4189 women between 20 and 44 years of age with a first-time fracture diagnosis, matched them with 4189 random controls using the Disease Analyzer database and investigated the relation with DMPA exposure. RESULTS: Overall, 11 % of the fracture cases and 7.7 % of the controls had DMPA use recorded. The adjusted OR for developing a fracture in patients with current use of DMPA compared to non-users was 0.97 (95 % CI 0.51-1.86), 2.41 (95 % CI 1.42-4.08), and 1.46 (95 % CI 0.96-2.23) for 1-2, 3-9, and ≥10 prescriptions, respectively. The adjusted OR for developing a fracture in patients with past use of DMPA compared to non-users was 0.96 (95 % CI 0.73-1.26), 1.14 (95 % CI 0.86-1.51), and 1.55 (95 % CI 1.07-2.27) for 1-2, 3-9, and ≥10 prescriptions, respectively. The highest fracture risk was identified in young patients less than 30 years with longer DMPA exposure (≥10 prescriptions; OR 3.04, 95 % CI 1.36-6.81), as well as in patients in the late reproductive years with past use of DMPA (OR 1.72, 95 % CI 1.13-2.63). CONCLUSIONS: Our results indicate that DMPA exposure is associated with increased fracture risk and may have negative effects on bone metabolism, resulting in impaired bone mineral acquisition during adolescence and accelerated bone loss in adult life.

Objective Measurement of Inaccurate Condom Use Reporting Among Women Using Depot Medroxyprogesterone Acetate for Contraception.

Observational analyses have suggested that women using the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may have heightened risk of acquiring HIV. However, those analyses were potentially confounded by sexual behavior, with possible differential condom use and reporting by women using DMPA versus no contraception. In a cross-sectional study, we measured the presence of a biomarker of recent condomless sex (Y chromosomal [Yc] DNA) in vaginal swabs from HIV-uninfected African women who had an HIV-infected partner and reported 100 % condom use. Half of the samples tested were from women reporting DMPA and half were from women using no contraception. Among 428 specimens tested (213 from DMPA users and 215 from women using no contraception), 32.0 % had Yc DNA detected, with a mean of 193 copies/10,000 human cells (range 0.1-8201). The frequency of detection did not differ by contraceptive use: 34.2 % of DMPA users versus 29.8 % of women using no contraception, adjusted odds ratio 1.3 (95 % confidence interval 0.9-2.0). These results suggest that inaccurate reporting of condom use by DMPA users may not account for the heightened risk of HIV acquisition among DMPA users in some observational studies.

Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF162p3 viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings.

BACKGROUND: Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. METHODS: Mucosal tenofovir (TFV) levels were compared in SHIVSF162p3 -negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF162p3 -positive DMPA-treated (n=6) and normally cycling (n=5) macaques. RESULTS: Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105  ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. CONCLUSIONS: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.

Correlation between uterine artery Doppler indices and menstrual irregularities among levonorgestrel releasing intrauterine system and depot medroxyprogesterone acetate users: a prospective observational study.

OBJECTIVE: To ascertain whether menstrual irregularities among users of levonorgestrel releasing intrauterine system (LNG-IUS) and depot medroxyprogesterone acetate (DMPA), were associated with changes in uterine artery Doppler indices or not. METHODS: This three-year prospective observational study included 102 women using LNG-IUS and 104 women using DMPA for contraception. Participants were followed at regular intervals over three years with performance of transvaginal ultrasound to measure uterine artery pulsatility index (PI) and resistance index (RI) before starting the method and at six months, 12 months, two and three years thereafter. Data was collected and tabulated. RESULTS: Significant changes in uterine artery PI and RI were detected. PI indices were reduced after six months of use in both groups and elevated significantly at 12 months in both groups compared to initial values (p < .001) while RI significantly reduced after six months in both groups and elevated significantly at 12 months, two and three years in both groups compared to initial values (p < .001). Both PI and RI significantly reduced in women suffered abnormal uterine bleeding and significantly elevated in women experienced amenorrhea irrespective of the method used (p < .001). CONCLUSIONS: LNG-IUS and DMPA induce hemodynamic changes in the uterine arteries denoting positive correlation with menstrual irregularities. Larger multicentre studies are warranted to potentiate our findings.

Effects of the copper intrauterine device versus injectable progestin contraception on pregnancy rates and method discontinuation among women attending termination of pregnancy services in South Africa: a pragmatic randomized controlled trial.

BACKGROUND: The copper intrauterine device (IUD) is under-utilised in South Africa, where injectable progestin contraception (IPC) dominates contraception usage. There is a lack of robust comparative data on these contraceptive options to inform policy, programs, clinical counseling, and women's choices. METHODS: Within the context of a South African program to increase women's access to the IUD, we conducted a pragmatic, open-label, parallel-arm, randomised controlled trial of the IUD versus IPC at two South African hospitals. The target sample size was 7,000 women and the randomisation ratio was 1:1. The random sequence was computer-generated and group allocation was concealed in sealed, opaque, consecutively-numbered envelopes. Counselled, consenting women attending termination of pregnancy services were randomly assigned to IUD or IPC immediately post-termination. Condoms were promoted for the prevention of sexually-transmitted infections. The primary outcome was pregnancy; secondary outcomes were discontinuation, side-effects, and HIV acquisition and disease progression. Pregnancy and discontinuation outcomes are reported here. RESULTS: The trial closed early with 2,493 participants randomised (IUD = 1,247, IPC = 1,246), due to international concerns regarding a possible association between IPC and HIV acquisition. Median follow-up was 20 months; 982 and 1000 participants were followed up in the IUD and IPC groups, respectively. Baseline group characteristics were comparable. Pregnancy occurred significantly less frequently among women allocated to the IUD than IPC: 56/971 (5.8%) versus 83/992 (8.4%), respectively; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96; P = 0.025. There were more protocol violations in the IUD group; however, discontinuation rates were similar between IUD and IPC groups (141/855 [16.5%] and 143/974 [14.7%], respectively). Women in the IUD group were more likely to discontinue contraceptive use due to abdominal pain or backache and non-specific symptoms, and those in the IPC group due to oligo- or amenorhoea and lack of sexual activity. CONCLUSIONS: The IUD was significantly more effective in preventing pregnancy than IPC. Efforts to expand contraception options and improve access to the IUD in settings where it is under-utilised are worthwhile. This trial shows that randomising long-acting, reversible contraceptives is feasible. TRIAL REGISTRATION: Pan African Clinical Trials Registry number PACTR201409000880157 (04-09-2014).

Experiences of "Antara": The Injectable Contraceptive in Rural Indian Women Presenting to a Tertiary Care Hospital of Eastern India.

Introduction: Depot medroxy progesterone acetate (DMPA) is an injectable contraceptive with well-proven effectiveness and excellent safety profile. It is marketed as Antara in India as a part of the government's family planning programme. Purpose: This study aimed to assess the experiences of women using Antara (DMPA) at a tertiary care hospital of Eastern India. Materials and methods: An institution-based retrospective cross-sectional study was carried out in the family planning unit of the study institution from April 2021 to October 2022 among 200 women of reproductive age. Each of the mothers was administered a researcher-administered questionnaire containing questions pertaining to their sociodemographic characteristics and Antara use experience. Results: The mean age of the study participants was 26.4 ± 5.9 years. Most of the participants were Hindus (55.0%), homemakers by their occupation (86.0%), and from lower socio-economic status. A significant proportion of the women had no formal education (14.0%) or had below primary education (14.5%). The most common reason provided by the participants for the discontinuation of Antara was the incidence of various side effects such as irregular menstruation, amenorrhea and apprehension. Lower educational status (p value < 0.001), poorer socio-economic status (p value < 0.001), and interval period starting of Antara (p value < 0.001) were statistically significantly associated with the discontinuation of the contraceptive. Conclusions: Most women who started taking DMPA (Antara) discontinued due to the fear of side effects. Therefore, the focus should be to educate women regarding the benefits and side effects of DMPA through proper counselling.

Injectable Contraceptives as an Underutilized Option for Women's Reproductive Health: An Exploratory Qualitative Study.

BACKGROUND: Injectable contraceptives (IC) provide a highly effective, reversible method of preventing conception, yet discontinuation rates are high. Health workers play a crucial role in the successful implementation of family welfare services. Adding up the basket of choices without knowing the community's needs can lead to poor utilization of services. OBJECTIVES: To explore the facilitators and barriers to the utility of injectable contraceptives among reproductive women from the user's point of view and to understand solutions from the key informants. METHODOLOGY: The study was conducted in the field practice areas among reproductive women attending a primary health center in Puducherry. It was an exploratory qualitative study in which in-depth interviews were conducted among 19 IC users using an interview guide. This was followed by a key informant interview with seven service providers, including doctors, staff nurses, auxiliary nurse midwives, and Anganwadi workers, to explore the solutions for the identified barriers. Purposive, convenient sampling was adopted for the selection of study participants, and the sample size was chosen until the point of saturation. Two investigators trained in qualitative research have performed a manual content analysis of transcripts to ensure credibility. Descriptive codes were derived, and similar codes were merged into categories and themes. RESULTS: The most common facilitators were awareness from service providers and dissatisfaction with previous methods. Fear of side effects, inadequate information, out-of-pocket expenditure, lack of family support, and sociocultural myths were the most common barriers. Key informants suggested counseling on side effects, incentive-based follow-up, universal health insurance, couple-based counseling, training of service providers, and a positive deviance approach. CONCLUSION: Health workers are pivotal in the successful delivery of family welfare services. The acceptability of IC could be improved by addressing concerns about side effects and its effective management through various targeted interventions.

Determinants of DMPA-SC self-care/self-injectable contraceptive uptake among modern contraceptive users in Burkina Faso: findings from the 2021 demographic and health survey.

Introduction: This study aimed to identify the determinants that influence the use of DMPA-SC/Sayana Press among women who use modern contraceptive methods in Burkina Faso. Methods: This study used secondary data obtained from the 2021 Burkina Faso Demographic and Health Survey (EDSBF). The dependent variable is the use of DMPA-SC among women aged 15-49 who employ modern contraceptive methods. The descriptive analysis used percentages to describe the study variables. The Pearson chi-square test was used to assess the associations between the explanatory variables and the study variable of interest. Bivariate logistic regression was used to examine the crude odds ratios of each explanatory variable with respect to the dependent variable. The multivariate model was used to determine the net effect of each independent variable on the dependent variable. The significance levels were defined at p < 0.05, with corresponding confidence intervals. Results: The study revealed significant differences in the use of DMPA-SC according to age, marital status, region of residence, level of education, number of children, and involvement in contraceptive decision-making within the couple. Younger women (aged 15-29 aOR = 2.12, p < 0.001)) and women aged 30-39 (aOR = 1.51, p = 0.02) are also more likely to use DMPA-SC compared to those aged 40-49. Married women or those living with a partner [aOR = 1.93 (1.22, 3.05)] are more likely to use DMPA-SC. Women with 1-3 children are twice as likely to use DMPA-SC as those without children (aOR = 1.97, p = 0.02). Region and Wealth Index were significantly associated with DMPA-SC use. The Boucle du Mouhoun region showed a significantly higher likelihood of DMPA-SC use (aOR = 8.10) and women in the highest wealth group are significantly less likely to use DMPA-SC (aOR = 0.59, p = 0.001). Conclusion: These results demonstrated the importance of adapting interventions to account for socio-demographic, regional, and cultural differences. This will enable the provision of services to the entire female population in a fair and equitable manner, while also addressing the limitations and enhancing the understanding of the underlying factors influencing the use of DMPA-SC.