Use of injectable progestin contraception and risk of STI among South African women

Objective

This study was conducted to determine the association between the use of injectable progestin contraception (IPC) and the risk of infection with Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), bacterial vaginosis (BV) and Trichomonas vaginalis (TV) among women in South Africa.

Methods

From August 1999 through May 2001, 643 HIV-1-negative women were recruited from family planning clinics in Orange Farm, South Africa. IPC [norethisterone enanthate (NET-EN) and depot medroxyprogesterone acetate (DMPA)] users and nonhormonal contraception users were recruited in approximately equal numbers. Eligible participants were seen at enrolment and on four follow-up visits over a 12-month period; 567 returned for at least one follow-up visit. Multivariable Poisson regression models with generalized estimating equations were used to compute the incidence rate ratios (IRRs) for infections with GC, CT, BV and TV by use of NET-EN or DMPA relative to nonuse during follow-up.

Results

In multivariable models, the use of DMPA slightly increased the risk of infection with CT [IRR=1.24; 95% confidence interval (95% CI)=0.80–1.94] and GC (IRR=1.30; 95% CI=0.58–2.98), although these associations were not statistically significant. In contrast, DMPA appeared to be protective for TV (IRR=0.35; 95% CI=0.12–1.01), although this estimate was very imprecise. The use of both DMPA and NET-EN was associated with a decreased risk of BV.

Conclusions

The use of DMPA among women in this study population was associated with an increased — but not statistically significant — risk of cervical infection with chlamydia and gonorrhea, and a decreased risk of TV and BV. Given the inconsistencies and limitations of the data describing an increased risk of CT and GC with IPC use, the potential risk of sexually transmitted infections (STIs) must be balanced against the risk of unintended pregnancy and its health consequences, especially in developing countries. Women opting to use IPC should be counseled to use condoms to protect against STIs and HIV.     

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.     

Depot Medroxyprogesterone Acetate Use Is Not Associated With Risk of Incident Sexually Transmitted Infections Among Adolescent Women

PurposeTo determine whether depot medroxyprogesterone acetate (DMPA) use is associated with an increased risk of acquisition of sexually transmitted infections (STIs) in a cohort of healthy adolescents, for whom prospective evidence is sparse.MethodsAdolescent women aged 14–17 years (n = 342) were recruited from clinical sites in the United States between 1999 and 2005. They returned quarterly for interviews and STI testing. During alternating 3-month periods, participants also completed daily diaries of sexual behaviors and performed weekly vaginal self-obtained swabs to test for STIs. Data collected through 2009 (median follow-up length = 42.2 months) were analyzed. Univariable and multivariable tests of association between STI acquisition during the 3-month diary period and covariates were calculated, using nonlinear mixed-effect logistic regression models to control for repeated measurements.ResultsIn multivariable analysis, there were no significant associations between DMPA use in the current or previous 3-month period and incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. The number of total or unprotected sexual events during the diary period was not associated with the risk of STI. Older age was a protective factor for the development of Chlamydia trachomatis (odds ratio = .85; 95% confidence interval = .76–.96). The only factor significantly associated with an increased risk of contracting all three STIs was a greater number of sexual partners during the diary period (odds ratio, range = 1.91–2.62).ConclusionsIn this U.S.-based cohort of adolescent women, we found no evidence that DMPA use was associated with increased STI risk. Efforts to curb STI transmission among adolescents should focus on education about the reduced number of sexual partners.     

The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women

BackgroundDepot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of fractures; however, nothing is known about the risk associated with intrauterine contraceptive device (IUD) use.Study DesignCase-control study. All women with a fracture (n=64,548) in the year 2000 in Denmark served as cases. For each case, three age-matched controls were randomly drawn from the general population (n=193,641). Exposure was present or previous DMPA or IUD use (only IUD coated with hormones, not those coated solely with copper). Adjustments were made for confounders.ResultsDMPA use seemed to be associated with an increased risk of fractures [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.01–2.06], while IUD use appeared to be associated with a decreased risk of fractures (OR=0.75, 95% CI: 0.64–0.87).ConclusionDMPA use may cause an increased risk of fracture. However, the fact that use of DMPA is rare in Danish women and the lack of baseline data including smoking status and BMI does not allow causal inferences to be made. Likewise, the seemingly decreased risk of fractures with IUD use is probably not a pharmacological effect but rather the effect of residual confounding related to nonincluded confounders regarding lifestyle.     

Investigating SARS-CoV-2 transmission among co-workers in a University of Northern Italy during COVID-19 pandemic: an observational study

Background:This study aimed to investigate SARS-CoV-2 transmission among co-workers at the University of Genoa, Italy, during the second COVID-19 pandemic wave.Methods:A cross-sectional study was carried out in October 2020 – March 2021: RT-PCR confirmed cases of COVID-19 notified to the Occupational Health Service were included in the analysis.Results:Among the n = 201 notified cases, contact tracing of n = 53 individuals identified n = 346 close contacts. The household setting (IRR = 36.8; 95% CI: 4.9-276.8; p < 0.001) and sharing eating areas (IRR = 19.5; 95% CI: 2.5-153.9; p = 0.005) showed the highest Secondary Attack Rates (SARs) compared to the office setting. Fatigue (IRR= 17.1; 95% CI: 5.2-55.8; p < 0.001), gastrointestinal symptoms (IRR= 6.6; 95% CI: 2.9-15.2; p< 0.001) and cough (IRR= 8.2; 95% CI: 3.7-18.2; p= p< 0.001) were associated with transmission of infection. Polysymptomatic cases (IRR= 23.1; 95% CI: 3.1-169.2; p = 0.02) were more likely to transmit the infection. Among COVID-19 index cases aged >60 years (OR = 7.7; 95% CI: 1.9-31.9; p = 0.0046) SARs were higher than in other age groups. Wearing respiratory protections by both the case and the close contact resulted an effective measure compared with no use (IRR = 0.08; 95% CI: 0.03-0.2; p = < 0.0001). Conclusions: Accurate infection monitoring and contact tracing was useful to identify the main situationsConclusions:Accurate infection monitoring and contact tracing was useful to identify the main situations of SARS-CoV-2 transmission in the workplace, and hence for risk assessment and prevention programs.     

The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses

ObjectiveWe evaluated the inter-rater reliability (IRR) of assessing the quality of evidence (QoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Study Design and SettingOn completing two training exercises, participants worked independently as individual raters to assess the QoE of 16 outcomes. After recording their initial impression using a global rating, raters graded the QoE following the GRADE approach. Subsequently, randomly paired raters submitted a consensus rating.ResultsThe IRR without using the GRADE approach for two individual raters was 0.31 (95% confidence interval [95% CI] = 0.21–0.42) among Health Research Methodology students (n = 10) and 0.27 (95% CI = 0.19–0.37) among the GRADE working group members (n = 15). The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher, that is, 0.66 (95% CI = 0.56–0.75) and 0.72 (95% CI = 0.61–0.79), respectively. The IRR further increased for three (0.80 [95% CI = 0.73–0.86] and 0.74 [95% CI = 0.65–0.81]) or four raters (0.84 [95% CI = 0.78–0.89] and 0.79 [95% CI = 0.71–0.85]). The IRR did not improve when QoE was assessed through a consensus rating.ConclusionOur findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system.     

Association between soy products,fruits, vegetables,and dairy products and gastric cancer risk in Helicobacter pylori-infected subjects: a case-control study in Korea

BACKGROUND/OBJECTIVESConsumption of certain protective foods may help inhibit Helicobacter pylori (H. pylori) associated gastric pathologies. However, studies conducted to assess the efficacy of protective foods in H. pylori-infected subjects are either limited or inconsistent. This study evaluated the association of individual or a combination of protective foods on the incidence of gastric cancer (GC) in H. pylori-positive subjects through a case-control study.MATERIALS/METHODSSubjects aged 20–79 years were selected from 2 hospitals between December 2002 and September 2006. In total, 134 patients and 212 controls tested positive for H. pylori infection. Among these, we included 82 pairs of cases and controls matched by sex, age (± 5 years), enrollment period (± 1 years), and hospital.RESULTSA higher intake of soy products was associated with a significantly lower risk of GC than a lower intake of soy products (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.14–0.96). Additionally, a higher fruit intake resulted in a significantly lower risk of GC than a lower fruit intake (OR = 0.35, 95% CI = 0.13–0.94). A combination of food groups was evaluated, and a lower risk of GC was observed with a high intake of both soy products and fruits (OR = 0.20, 95% CI = 0.06–0.67), high intake of soy and dairy products (OR = 0.28, 95% CI = 0.10–0.78) and high intake of fruits and dairy products (OR = 0.28, 95% CI = 0.09–0.83).CONCLUSIONSA high intake of soy products or fruits was associated with a lower risk of GC. A combination of soy products or fruits with dairy products was associated with a lower risk of GC. A balanced intake of soy products, fruits, and dairy products may help reduce GC risk.     

Pituitary response to LHRH in long-term users of injectable contraceptives

The site of gonadotrophin inhibition in longterm users of injectable contraceptives is still debatable. The pituitary response to LHRH (50 ug, I.V.) was assessed in 32 women. Sixteen cases were using either medroxyprogesterone acetate (DMPA; n = 8 150 mg I.M. every three months) or norethisterone enanthate (NET-EN; n = 8, 200 mg every 2 months) for at least 18 months. The remaining cases (n = 16) were normal fertile females not using any hormonal contraceptive (control group). The pituitary response to LHRH injection in both injectable subgroups was nearly identical to that in the control group. Neither the basal levels nor the net increase in gonadotrophins following LHRH injection were significantly different in the study groups from those of the control group. Long-term use of DMPA or NET-EN does not affect the pituitary responsiveness to LHRH injection and the pituitary is not a primary site for ovulation inhibition in these cases.     

Longer Family Participation in WIC is Associated With Lower Childhood Sugar-Sweetened Beverage Intake

ObjectiveTo evaluate if children of families with a longer duration of participation in the Special Supplementation Nutrition Program for Women, Infants, and Children (WIC) consume fewer sugar-sweetened beverages (SSB) and more water.DesignA repeated cross-sectional study.SettingConducted among representative samples of WIC-participating families in Los Angeles County, California, in 2014, 2017, and 2020.ParticipantsChildren aged 4–59 months participating in WIC.Main Outcome MeasuresDaily servings of total SSBs, daily servings of specific types of SSBs, and daily servings of water.AnalysisMultivariable count regression models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations of the duration of family WIC participation with daily servings of total SSBs, water, and specific types of SSBs. Zero-inflated negative binomial regression models were used for total SSBs and specific types of SSBs, and Poisson regression was used for water.ResultsChildren of families with 2 years of WIC participation consumed significantly fewer daily servings of total SSBs (IRR, 0.95; 95% CI, 0.93–0.98; P = 0.002), fruit-flavored SSBs (IRR, 0.95; 95% CI, 0.91–0.99; P = 0.02), soda (IRR, 0.86; 95% CI, 0.76–0.98; P = 0.02), and water (IRR, 0.99; 95% CI, 0.98 to < 1.00; P = 0.03) than children of families with 1 year of WIC participation. Protective associations for total SSBs, fruit-flavored SSBs, and soda remained statistically significant and increased in magnitude through 10 years of family WIC participation.Conclusions and ImplicationsDuration of WIC participation was associated with decreased SSB intake by young children. Given the role that increasing water intake in lieu of SSBs plays in child obesity, improving the effectiveness of WIC nutrition education on parental perceptions and provision of fruit-flavored SSBs and water to their children merits detailed evaluation.     

Bone mineral density in a cohort of adolescents during use of norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives and after discontinuation of norethisterone enanthate

Background

Depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN) and combined oral contraceptives (COCs) have been shown to have a negative effect on bone mineral density (BMD) in adolescents. The aim of this study was to investigate BMD in 15- to 19-year-old new users of DMPA, NET-EN and COCs.

Study Design

This 5-year longitudinal study followed up new users of DMPA (n=115), NET-EN (n=115) and COCs (n=116) and 144 nonuser controls. BMD was measured at the distal radius using dual-energy X-ray absorptiometry.

Results

BMD increased in all groups (annual percent increase: nonusers, 1.49%; DMPA, 1.39%; NET-EN, 1.03%; COCs, 0.84%) during follow-up (p<.001). There was evidence for lower BMD increases per annum in NET-EN (p=.050) and COC (p=.010) users compared to nonusers but no difference between DMPA and nonusers (p=.76). In 14 NET-EN discontinuers, an overall reduction of 0.61% per year BMD was followed upon cessation by an increase of 0.69% per year (p=.066).

Conclusion

This study suggests that BMD increases in adolescents may be less in NET-EN and COC users; however, recovery of BMD in NET-EN users was found in the small sample of adolescents followed post-discontinuation.     

At Surgeons' Sessions: A Focus on Adjunctive Immunotherapy

Abstract

Background: Antimuscarinic drug prescribing scoring systems might better identify patients at risk of adverse drug reactions. The recently developed Anticholinergic Risk Scale (ARS) score is significantly associated with the number of antimuscarinic side effects in older outpatients. We sought to identify the clinical and demographic patient-level correlates of the ARS, including a modified version adjusted for daily dose, in elderly hospitalized patients. Methods: Clinical and demographic patient characteristics known to be associated with antimuscarinic prescribing, ARS and dose-adjusted ARS scores, and full medication exposure on admission were recorded in 362 consecutive patients (aged 83.6 ± 6.6 years) admitted to 2 geriatric units (NHS Grampian, Aberdeen, Scotland, UK) between February 1, 2010 and June 30, 2010. Results: Each year of increasing age was associated with reduced number of antimuscarinic drugs (incidence rate ratio [IRR], 0.963; 95% confidence interval [CI], 0.948–0.980; P < 0.001), non-antimuscarinic drugs (IRR, 0.991; 95% CI, 0.985–0.997; P = 0.006), and total number of drugs (IRR, 0.988; 95% CI, 0.983–0.994; P < 0.001). Multivariate Poisson regression showed that increasing age and history of dementia were negatively associated with the ARS score (IRR, 0.97; 95% CI, 0.94–0.99; P = 0.001 and IRR, 0.62; 95% CI, 0.41–0.92; P = 0.019, respectively). By contrast, institutionalization (IRR, 1.32; 95% CI, 1.00–1.74; P = 0.050), Charlson comorbidity index (IRR, 1.06; 95% CI, 1.01–1.11; P = 0.015), and total number of non-antimuscarinic drugs (IRR, 1.13; 95% CI, 1.08–1.18; P < 0.001) were all positively associated with the ARS score. Similar results were observed for the dose-adjusted ARS score. Conclusion: Institutionalization, comorbidities, and non-antimuscarinic polypharmacy show independent positive associations with the ARS and dose-adjusted ARS scores in older hospitalized patients. Increasing age and dementia are negatively associated with the ARS score.     

Counting the costs: Comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa

Background

In South Africa, where health care resources are limited, it is important to ensure that drugs provision and use is rational. The Essential Drug List includes depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN) as injectable progestagen-only contraceptives (IPCs), and both products are extensively used.

Objectives and Methods

Utilisation patterns of the injectable contraceptive products DMPA and NET-EN are compared in the context of current knowledge of the safety and efficacy of these agents. Utilisation patterns were analysed by means of a Pareto (ABC) analysis of IPCs issued from 4 South African provincial pharmaceutical depots over 3 financial years. A case study from rural KwaZulu-Natal, South Africa, is used to examine utilisation patterns and self-reported side effects experienced by 187 women using IPCs.

Results

IPCs accounted for a substantial share of total state expenditure on drugs. While more DMPA than NET-EN was issued, NET-EN distribution from 2 depots increased over the 3-year period. Since DMPA was cheaper, if all NET-EN clients in the 1999/2000 financial year (annualised) had used DMPA, the 4 depots could have saved 4.95 million South African Rands on product acquisition costs alone. The KZN case study showed slightly more NET-EN (54%) than DMPA (46%) use; no significant differences in self-reported side effects; and that younger women were more likely to use NET-EN than DMPA (p = 0.0001).

Conclusions

Providing IPCs on the basis of age is not appropriate or cost effective. Rational use of these products should include consideration of the cost of prescribing one over another.     

Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.     

“NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis.”

Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including 12,043 DT cancer cases and 15,209 healthy controls were included in the present meta- analysis. Results of meta-analysis revealed a significant association between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models (T vs. C: OR = 1.21, 95% CI = 1.11–1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI = 1.22–1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12–1.35, p < 0.001; TT vs. CT + CC: OR = 1.36, 95% CI = 1.15–1.60, p < 0.001; CT vs. CC: OR = 1.16, 95% CI = 1.07–1.27, p < 0.001). In the stratified analysis based on cancer types, significant associations were observed between NQO1 C609T polymorphism and GC (OR = 1.38, 95% CI = 1.11–1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06–1.30, p = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99–1.35, p = 0.06). Furthermore, stratified analysis based on ethnicity indicated that there was a significant association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT vs. CC: OR = 1.55, 95% CI = 1.21–2.00, p ≤ 0.001) as well as in Caucasian populations (TT vs. CC: OR = 1.34, 95% CI = 1.04–1.73, p = 0.02). In conclusion, the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk factor for DT cancers, including GC and CRC.     

Effectiveness of a Universally Offered Chlamydia and Gonorrhea Screening Intervention in the Pediatric Emergency Department

PurposeAdolescents represent more than half of the newly diagnosed sexually transmitted infections in the U.S. annually. Emergency departments (EDs) may serve as an effective, nontraditional setting to screen for chlamydia/gonorrhea (CT/GC). The objective was to evaluate the effectiveness of a universally offered CT/GC screening program in two pediatric ED settings.MethodsThis was a prospective, delayed start pragmatic study conducted over 18 months in two EDs within the same academic institution among ED adolescents aged 14–21 years with any chief complaint. Using a tablet device, adolescents were confidentially informed of CT/GC screening recommendations and were offered screening. If patients agreed to CT/GC testing, a clinical decision support tool was triggered to inform the provider and order testing. The main and key secondary outcomes were the proportion of CT/GC testing and positive CT/GC test results in each respective ED.ResultsBoth EDs experienced modest but statistically significant increases in CT/GC testing post- versus pre-intervention (main: 11.5% vs. 7.9%; confidence interval [CI]: 2.9–4.2; p < .0001 and satellite: 3.8% vs. 2.6%; 95% CI: .7–1.7; p < .0001). Among those tested, the positivity rate at the main ED did not significantly change post- versus pre-intervention (24.1% vs. 23.2%; 95% CI: ?1.9 to 3.8; p = .71) but significantly decreased at the satellite ED (7.6% vs. 14.8%; 95% CI: ?12.2 to ?2.2; p = .01).ConclusionsA universally offered screening intervention increased the proportion of adolescents who were tested at both EDs and the detection rates for CT/GC at the main ED, but patient acceptance of screening was low.     

When can a woman have repeat progestogen-only injectables-depot medroxyprogesterone acetate or norethisterone enantate?

Background

Currently, there is a generally accepted 2-week grace period for women returning early/late for reinjection of either depot medroxyprogesterone acetate (DMPA) or norethisterone enantate (NET-EN). This systematic review evaluates the evidence regarding return to fertility and ovulation after injection of a progestogen-only contraceptive.

Study Design

We searched the PubMed database to identify all relevant evidence published in peer-reviewed journals from database inception through November 2008 regarding timing of fertility and return to ovulation after the last injection of DMPA or NET-EN.

Results

We identified 20 articles, 10 on DMPA use, eight on NET-EN use and two examining both types of injectables. Six studies examining time to pregnancy after discontinuing DMPA or NET-EN reported that pregnancy rates during the currently recommended 2-week grace period were zero or very low. Studies of return to ovulation indicated a wide variation in time to ovulation post-injection with the majority ranging from 15-49 weeks from the last injection (for DMPA) and 4.9-24.3 weeks from the last injection (for NET-EN). Limitations of this body of evidence include small sample sizes, lack of data on the main outcome of interest (time to pregnancy) and inconsistency in measurement of ovulation, a surrogate measurement for pregnancy risk.

Conclusion

Studies evaluating time to pregnancy after last injection of DMPA or NET-EN reported extremely low pregnancy rates during the 2-week interval following the reinjection date; extremely low pregnancy rates for DMPA were also reported for 4 weeks following the reinjection date. Studies of return to ovulation after last injection of DMPA generally found that the earliest ovulation did not occur until several months after the last injection while studies of NET-EN reported ovulations around (or even before) the time for reinjection.     

The safety of intrauterine contraception initiation among women with current asymptomatic cervical infections or at increased risk of sexually transmitted infections

ObjectiveThe objective was to assess risk of pelvic inflammatory disease (PID) among women with current asymptomatic undiagnosed cervical infection or who are at high risk of sexually transmitted infections (STIs), comparing those who have a copper-bearing (Cu-) or levonorgestrel (LNG-) intrauterine device (IUD) placed with women who do not.Study designWe searched PubMed and Cochrane Library for articles from January 1984 through January 2016 addressing our objective. We assessed study quality using the United States Preventive Services Task Force evidence grading system.ResultsOur search strategy yielded 2220 articles, of which 10 met inclusion criteria. Two studies provided direct evidence of PID rates in women with undiagnosed gonococcal or chlamydial (GC/CT) infection or at high risk for STIs initiating IUDs versus other contraceptive methods (level II-2, fair to poor), and neither study found a difference. Eight studies provided indirect evidence (II-2 to II-3, fair to poor). One study found no difference in PID rates between initiators of Cu- versus LNG-IUDs. Five studies compared algorithms based on patient factors with laboratory GC/CT screening to predict cervical infection. Based on likelihood ratios, none of these algorithms adequately identified women at high risk of asymptomatic cervical infection who should not undergo IUD placement. Two studies compared IUD placement on the same day as STI screening with delayed placement after screening and found no difference in PID rates.ConclusionLimited evidence suggests that IUD placement does not increase the risk of PID compared with no IUD placement among women with asymptomatic undiagnosed cervical infection or at high risk of STIs. Algorithms based on patient characteristics to identify women with asymptomatic GC/CT may be overly restrictive, leading to missed opportunities for IUD initiation. Historical concerns about higher PID risk among women at risk for STIs who use IUDs may not be relevant with modern devices and STI screening and treatment practices.     

Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence

Whether use of various types of hormonal contraception (HC) affect risk of HIV acquisition is a critical question for women's health. For this systematic review, we identified 22 studies published by January 15, 2014 which met inclusion criteria; we classified thirteen studies as having severe methodological limitations, and nine studies as “informative but with important limitations”. Overall, data do not support an association between use of oral contraceptives and increased risk of HIV acquisition. Uncertainty persists regarding whether an association exists between depot-medroxyprogesterone acetate (DMPA) use and risk of HIV acquisition. Most studies suggested no significantly increased HIV risk with norethisterone enanthate (NET-EN) use, but when assessed in the same study, point estimates for NET-EN tended to be larger than for DMPA, though 95% confidence intervals overlapped substantially. No data have suggested significantly increased risk of HIV acquisition with use of implants, though data were limited. No data are available on the relationship between use of contraceptive patches, rings, or hormonal intrauterine devices and risk of HIV acquisition. Women choosing progestin-only injectable contraceptives such as DMPA or NET-EN should be informed of the current uncertainty regarding whether use of these methods increases risk of HIV acquisition, and like all women at risk of HIV, should be empowered to access and use condoms and other HIV preventative measures. Programs, practitioners, and women urgently need guidance on how to maximize health with respect to avoiding both unintended pregnancy and HIV given inconclusive or limited data for certain HC methods.     

Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective Analysis

BackgroundCOVID-19 messenger RNA (mRNA) vaccines have demonstrated efficacy and effectiveness in preventing symptomatic COVID-19, while being relatively safe in trial studies. However, vaccine breakthrough infections have been reported.ObjectiveThis study aims to identify risk factors associated with COVID-19 breakthrough infections among fully mRNA-vaccinated individuals.MethodsWe conducted a series of observational retrospective analyses using the electronic health records (EHRs) of the Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York City (NYC) adult residences with at least 1 polymerase chain reaction (PCR) record were included in this analysis. Poisson regression was performed to assess the association between the breakthrough infection rate in vaccinated individuals and multiple risk factors—including vaccine brand, demographics, and underlying conditions—while adjusting for calendar month, prior number of visits, and observational days in the EHR.ResultsThe overall estimated breakthrough infection rate was 0.16 (95% CI 0.14-0.18). Individuals who were vaccinated with Pfizer/BNT162b2 (incidence rate ratio [IRR] against Moderna/mRNA-1273=1.66, 95% CI 1.17-2.35) were male (IRR against female=1.47, 95% CI 1.11-1.94) and had compromised immune systems (IRR=1.48, 95% CI 1.09-2.00) were at the highest risk for breakthrough infections. Among all underlying conditions, those with primary immunodeficiency, a history of organ transplant, an active tumor, use of immunosuppressant medications, or Alzheimer disease were at the highest risk.ConclusionsAlthough we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Immunocompromised and male individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2 pandemic, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.     

Bone mineral density in adolescents using norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives for contraception

PURPOSE: Most studies have shown a negative effect of depot-medroxyprogesterone acetate (DMPA) on the bone mineral density (BMD) of adolescents. There is no information available on the effect of norethisterone enanthate (NET-EN) on BMD in adolescents and the effect of combined oral contraceptives (COCs) on adolescent BMD is inconclusive. The aim of this longitudinal study was to investigate BMD in adolescent (aged 15-19 years) new users of hormonal contraception (DMPA, NET-EN and COCs). METHOD: New users of DMPA (n=115), NET-EN (n=115), COCs (n=116) and 144 nonuser controls were recruited. BMD was measured at the distal radius and midshaft of the ulna using dual X-ray absorptiometry. RESULTS: In total, 275 women were included in this interim analysis and total follow-up time was 553 person-years. There was no significant difference in radius BMD between users of different contraceptive methods at baseline (p=.40). Overall, an increase in radius BMD of 0.00522 per person-year was observed. This result was similar when adjusting for BMI in the random effects regression model (p=.88). The regression model showed that BMI was significantly associated with radius BMD, with each unit increase in BMI corresponding to an increase of 0.0029 g/cm2 in BMD (95% CI 0.0023 to 0.0036, p<.001). Interaction between contraceptive method and follow-up time adjusted for BMI was not significant (p=.07). The increase in BMD for NET-EN users of 0.0013 g/cm2 per person-year (95% CI -0.0017 to 0.0043) was significantly lower than that of nonusers (p=.017). For DMPA and COC users, the increase in BMD was not significantly different compared to the nonusers. This study suggests that NET-EN users had lower increase in BMD over time compared to the other user groups.