Toward an intravaginal device to detect risk of preterm labor: a user-centered design approach in Sub-Saharan Africa.

BACKGROUND: Prematurity and its complications are the leading cause of death and disability in children under five in Africa and North America, affecting as many as one in ten pregnancies. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. In parallel with early-stage U.S.-based testing of a novel self-placed intravaginal device to predict PTB risk, we elicited key stakeholder input from two sub-Saharan African countries to ensure local contextual factors inform future development of the device and its acceptability. METHODS: A qualitative study was conducted in Kiambu County, Kenya and KwaZulu-Natal Province, South Africa. We conducted 26 focus group discussions with pregnant women (n = 132) and males from the community (n = 54); in-depth interviews with women who had a history of PTB (n = 10), healthcare providers (n = 16), and health system experts (n = 10). Interviews were transcribed and thematic analysis was performed using an iterative coding technique. In addition, we facilitated user-centered design sessions to generate prototype preferences. RESULTS: Women with a personal history of PTB were almost unanimous in support of the proposed device, whereas those with no experience of PTB expressed the greatest degree of reservation. Healthcare providers anticipated that women with a history of PTB would accept the device. However, various potential challenges were identified, including potential discomfort with device insertion, hygiene, and sexual activity, as well as need for provider training, and attention to country-specific regulatory processes. Both community participants and providers expressed a preference for a provider inserted device. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. CONCLUSIONS: Use of an intravaginal device to detect risk of PTB was generally acceptable, however stakeholders expressed a notable preference for insertion by providers. This reflects the significance of end-user consultation in device design and use. Recommended device modifications as well as educational messaging and provider technical assistance may facilitate utilization.

Prematurity and its complications are the leading cause of death and disability in children under 5 years of age. Up to ten percent of pregnancies in North America and Africa are affected. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. A U.S.-based study has developed an intravaginal device to detect preterm labor. In order to assess acceptability and guide development for a low-resource setting, a qualitative study was conducted in Kenya and South Africa. We conducted focus group discussions and interviews with pregnant women, male community members, health care providers and health systems experts. Participants with a personal history of PTB were almost unanimous in support of the proposed device; women with no experience of PTB expressed the greatest degree of reservation. Various potential challenges were identified: discomfort, hygiene, and sexual activity, the need for provider training and attention to country-specific regulatory processes. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. Stakeholders expressed a strong preference for insertion by providers. These findings reflect the significance of end-user consultation in device design and use.

Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. METHODS: Th BONE: CARE study was a prospective cohort study that recruited women aged 18-35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. FINDINGS: Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3·406% [95% CI -3·969 to -2·844] vs -1·111% [-1·929 to -0·293]; p<0·0001), total hip (-3·856% [-4·449 to -3·264] vs -1·714% [-2·479 to -0·949]; p=0·0002), and femoral neck (-4·422% [-5·078 to -3·766] vs -1·999% [-3·022 to -0·976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (-0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine -2·677% [95% CI -3·743 to -1·611]; p<0·0001; total hip -2·518% [-3·575 to -1·461]; p<0·0001; and femoral neck -2·907 [-4·132 to -1·683]; p<0·0001) or than controls (lumbar spine -4·970% [-6·391 to -3·549]; p<0·0001; total hip -4·151% [-5·579 to -2·724]; p<0.0001; and femoral neck -4·773% [-6·424 to -3·122]; p<0·0001) INTERPRETATION: Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV. FUNDING: National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1-Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda.

Most studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1-infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005-2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18-35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1-infected current DMPA users, (ii) HIV-1-infected previous DMPA users, (iii) HIV-1-infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1-infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1-infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1-uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1-infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤-2 at any of the three sites) compared with age-matched HIV-1-uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1-infected current DMPA users (5.6%-8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1-infected women in resource-limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Gender and Power Dynamics of Social Relationships Shape Willingness to Participate in Biomedical HIV Prevention Research Among South African Adolescents and Young Adults.

Background: Understanding young women and men's perceived barriers and facilitators to participation in biomedical HIV prevention research is important for designing youth friendly services (YFS) and acceptable technologies, which are necessary for preventing high sustained HIV incidence in South Africa. This study explores the multileveled barriers and facilitators to young men and women's willingness to participate in hypothetical biomedical HIV prevention research. Methods: Eight age- (16-18 and 19-24 years) and gender-stratified focus group discussions (FGDs) were conducted using semi-structured interview guides to explore young South African women and men's willingness, perceived barriers, and facilitators to participating in biomedical HIV prevention research. FGD transcripts were uploaded to NVivo and coded collaboratively with youth study team members. Thematic analysis using Bronfenbrenner's ecological model (individual, inter-personal, community, and societal) was used to guide a deductive coding procedure, which was documented and compared by gender. Results: Thirty-one participants from Durban and 34 from Soweto participated in FGDs. Individual facilitators for participation were discussed more by young men and included financial incentives and altruism. Concerns about side-effects of biomedical products were a common barrier. Interpersonal relationships with peers, intimate partners and caregivers influenced young people's willingness to participate in HIV prevention research, more so among young women. For young women, gendered power dynamics and distrust of intimate partners and parents influenced both communication regarding participation and willingness to participate in research that is often stigmatized, due to societal norms around women's sexuality. On a societal level, participants expressed distrust in medical and research institutions, however a sense of community that was developed with the study staff of this project, was a motivator to participate in future studies. Discussion: At each level of the ecological model, we found participants expressed gendered barriers and facilitators for participation. Gender norms as well as distrust of partners, parents, and health care professionals were key barriers that cut across all levels. At each level participants discussed facilitators that were youth-engaged, underscoring the need to implement YFS, establish trust and address gender inequities within future biomedical HIV prevention studies wishing to engage and retain South African youth.

Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status.

BACKGROUND: In South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40-49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status. METHODS: One hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years. RESULTS: There was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006). CONCLUSION: This study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.

Placing contraception at the centre of the HIV prevention agenda.

Over the past decade, the global response to the HIV epidemic has been unprecedented, and enormous progress has been made. Significant investment in the roll out of antiretroviral treatment (ART) and efforts to increase treatment coverage have greatly reduced the number of AIDS-related deaths worldwide. There are a growing number of promising innovations to expand the HIV prevention mix. However, the reach of these interventions is still very limited in adolescent girls and young women (15-24 years) and the full realisation of the intervention mandates has not yet been achieved. The HIV prevention field has been criticised for the tendency to adopt a narrow focus. The Fast-Track Strategy offers a unique opportunity for the HIV prevention field to broaden its gaze and to begin to identify synergies (and efficiencies) with prevention approaches from other global development priorities, namely sexual and reproductive health and rights (SRHR). This paper applies a SRHR lens to HIV prevention by highlighting the critical relationship between unintended pregnancy and HIV, and seeks to expand on earlier debates that prevention of HIV and prevention of unintended pregnancy are inextricably linked, complementary activities with interrelated and common goals. We call for the prioritisation of prevention of unintended pregnancy amongst two overlapping population groups - girls and young women (15-24 years old) and women living with HIV - as a key tactic to accomplish the Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track Strategy and as a way to fully realise existing HIV prevention efforts. We discuss the intersecting pathways between HIV prevention and unintended pregnancy prevention and build a case for contraception to be placed at the centre of the HIV prevention agenda.

Acceptability and performance of the menstrual cup in South Africa: a randomized crossover trial comparing the menstrual cup to tampons or sanitary pads.

BACKGROUND: In low-income settings, many women and girls face activity restrictions during menses, owing to lack of affordable menstrual products. The menstrual cup (MC) is a nonabsorbent reusable cup that collects menstrual blood. We assessed the acceptability and performance of the MPower® MC compared to pads or tampons among women in a low-resource setting. METHODS: We conducted a randomized two-period crossover trial at one site in Durban, South Africa, between January and November 2013. Participants aged 18-45 years with regular menstrual cycles were eligible for inclusion if they had no intention of becoming pregnant, were using an effective contraceptive method, had water from the municipal system as their primary water source, and had no sexually transmitted infections. We used a computer-generated randomization sequence to assign participants to one of two sequences of menstrual product use, with allocation concealed only from the study investigators. Participants used each method over three menstrual cycles (total 6 months) and were interviewed at baseline and monthly follow-up visits. The product acceptability outcome compared product satisfaction question scores using an ordinal logistic regression model with individual random effects. This study is registered on the South African Clinical Trials database: number DOH-27-01134273. RESULTS: Of 124 women assessed, 110 were eligible and randomly assigned to selected menstrual products. One hundred and five women completed all follow-up visits. By comparison to pads/tampons (usual product used), the MC was rated significantly better for comfort, quality, menstrual blood collection, appearance, and preference. Both of these comparative outcome measures, along with likelihood of continued use, recommending the product, and future purchase, increased for the MC over time. CONCLUSION: MC acceptance in a population of novice users, many with limited experience with tampons, indicates that there is a pool of potential users in low-resource settings.

Performance and safety of the second-generation female condom (FC2) versus the Woman's, the VA worn-of-women, and the Cupid female condoms: a randomised controlled non-inferiority crossover trial.

BACKGROUND: New designs of female condom have been developed to reduce costs and improve acceptability. To secure regulatory approvals, clinical studies are needed to verify performance. We aimed to assess the functional performance and safety of three new condom types-the Woman's Condom, the VA worn-of-women (wow) Condom Feminine, and the Cupid female condom-against the existing second-generation female condom (FC2). METHODS: We did a randomised controlled, non-inferiority, four-period crossover trial at three sites in Shanghai, China, and one site in Durban, South Africa, between May 1, 2011, and Jan 31, 2012. Participants aged 18-45 years who were sexually active, monogamous, not pregnant, and not sex workers, were eligible for inclusion if they were literate, had no known allergies to the study products; used a reliable, non-barrier method of contraception, and had no visible or reported sexually transmitted infections. We used a computer-generated randomisation sequence with a Williams square design of size four to assign patients (1:1:1:1) to the FC2 control device, or the Woman's, VA wow, or Cupid condoms, with 12 potential allocations. Randomisation was stratified by site. Participants were not masked to condom type, but allocation was concealed from study investigators. The primary non-inferiority endpoints were total clinical failure and total female condom failure, with a non-inferiority margin of 3%. Women were asked to use five of each condom type and were interviewed after use of each type. We also assessed safety data for each type. We did both per-protocol and intention-to-treat analyses. We calculated frequencies and percentages for each failure event and estimated differences in performance with a generalised estimating equation model. This study is registered, number DOH-27-0113-4271. FINDINGS: 616 women were assessed for eligibility, of whom 600 were randomly assigned to condom-type order (30, 120, and 150 women in the three sites in China, and 300 women in the site in South Africa). 572 women completed follow-up, with at least one condom of each type. Total female condom failure was 3·43% for FC2, 3·85% for the Woman's Condom (difference 0·42%, 90% CI -1·42 to 2·26), 3·02% for VA wow (-0·42%, -1·86 to 1·32), and 4·52% for Cupid (1·09%, -0·60 to 2·78); total clinical failure was 2·88%, 3·05% (0·17%, -1·48 to 1·81), 2·49% (-0·25%, -1·75 to 1·26), and 3·87% (0·99%, -0·55 to 2·52), respectively. Only two (<1%) participants, in South Africa, reported serious adverse events, unrelated to use of the study products. INTERPRETATION: Non-inferiority was shown for all condom failure events for the three new devices versus the FC2, within the predefined margin. FUNDING: Universal Access to Female Condoms (UAFC).

Using scratch card technology for random allocation concealment in a clinical trial with a crossover design.

BACKGROUND: To avoid selection bias in clinical trials, random allocation concealment is crucial to ensure that participants and or researchers remain unaware of assignments. PURPOSE: We aimed to design an allocation concealment method that reduced the possibility of selection bias for a randomized, open-label, crossover trial to evaluate device function of four female condom (FC) types. METHODS: Using scratch card technology, we devised a simple method of concealment, whereby the treatment sequence was printed on a single card for each participant, and the codes for each treatment in the sequence were concealed beneath foil squares on a stiff A6-sized card. On the first and subsequent follow-up visits, the foil corresponding to that visit was scratched from the square to reveal the condom type allocation for the next condom-use period. Staff in the South African and Chinese trial sites were trained in use and care of the card, and on completion of the study completed a questionnaire on their experience of use. RESULTS: Research staff in both countries found the card easy to use and those who had previously used the sequentially numbered, opaque, sealed envelopes (SNOSE) system for random allocation reported the scratch card easier to use. Research staff most commonly used a coin to remove the foil square and some used their fingernails. In both South Africa and China, no errors in allocation sequence were found during study monitoring. LIMITATIONS: Scratch card system of allocation cannot be printed in-house. CONCLUSIONS: This novel, effective method of concealment for a crossover random allocation was well liked by study staff. The most important advantage of this method is the ability to conceal consecutive allocations of a crossover design using a single card, thus eliminating the need for multiple envelopes per participant. While we used this method in a clinical trial of FCs, it could be employed in a range of other clinical trials and other randomized studies.

Hormonal contraceptive continuation and switching in South Africa: implications for evaluating the association of injectable hormonal contraceptive use and HIV.

Investigating the association between hormonal contraception and HIV is challenging due to high discontinuation rates among users. This secondary analysis of 262 South African adolescent new users of hormonal contraception found continuation rates after 1 year for depot medroxyprogesterone acetate, norethisterone enanthate, or combined oral contraceptives of 40.4%, 64.4%, and 64.6%, respectively. Implications for studies evaluating the association between injectable hormonal contraceptive use and HIV are discussed.

Key informant perspectives on policy- and service-level challenges and opportunities for delivering integrated sexual and reproductive health and HIV care in South Africa.

BACKGROUND: Integration of sexual and reproductive health (SRH) and HIV services is a policy priority, both globally and in South Africa. Recent studies examining SRH/HIV integration in South Africa have focused primarily on the SRH needs of HIV patients, and less on the policy and service-delivery environment in which these programs operate. To fill this gap we undertook a qualitative study to elicit the views of key informants on policy-and service-level challenges and opportunities for improving integrated SRH and HIV care in South Africa. This study comprised formative research for the development of an integrated service delivery model in KwaZulu-Natal (KZN) Province. METHODS: Semi-structured in-depth interviews were conducted with 21 expert key informants from the South African Department of Health, and local and international NGOs and universities. Thematic codes were generated from a subset of the transcripts, and these were modified, refined and organized during coding and analysis. RESULTS: While there was consensus among key informants on the need for more integrated systems of SRH and HIV care in South Africa, a range of inter-related systems factors at policy and service-delivery levels were identified as challenges to delivering integrated care. At the policy level these included vertical programming, lack of policy guidance on integrated care, under-funding of SRH, program territorialism, and weak referral systems; at the service level, factors included high client load, staff shortages and insufficient training and skills in SRH, resistance to change, and inadequate monitoring systems related to integration. Informants had varying views on the best way to achieve integration: while some favored a one-stop shop approach, others preferred retaining sub-specialisms while strengthening referral systems. The introduction of task-shifting policies and decentralization of HIV treatment to primary care provide opportunities for integrating services. CONCLUSION: Now that HIV treatment programs have been scaled up, actions are needed at both policy and service-delivery levels to develop an integrated approach to the provision of SRH and HIV services in South Africa. Concurrent national policies to deliver HIV treatment within a primary care context can be used to promote more integrated approaches.

Progress and challenges to male and female condom use in South Africa.

South Africa has responded to the sexually transmissible infection and HIV epidemic with a rapid expansion of its national-level public sector condom program. Male condoms are available widely at no cost in the public sector, with expanded access via social marketing and the private sector. The female condom program is one of the largest and best established globally. National surveys show progressive increases in rates of condom use at last sex. However, inconsistent and incorrect condom use and the likelihood that condoms are discontinued in longer-term partnerships are some of the challenges impeding the condom program's successes in the fight against sexually transmissible infections and HIV. This article reviews the current condom program, related guidelines and policies, and the existing data on male and female condom use, including distribution and uptake. We discuss the main challenges to condom use, including both user and service-related issues and finally how these challenges could be addressed.

"There's evidence that this really works and anything that works is good": views on the introduction of medical male circumcision for HIV prevention in South Africa.

Three clinical trials have demonstrated the partial efficacy (40-60%) of surgically conducted medical male circumcision (MMC) in preventing HIV transmission to circumcised men. This research formed part of a larger study exploring the importance of integration of sexual and reproductive health with HIV services. The objective was to elicit key informant views on the introduction of MMC for HIV prevention in South Africa. Twenty-one key informants representing the South African Health Department, local and international NGOs and universities, were asked, via semi-structured interviews about their views on introducing MMC as an HIV prevention strategy in South Africa. Interviews were transcribed and all discussions on MMC were coded for analysis using NVivo 8. The majority of the key informants were knowledgeable about MMC for HIV prevention and felt that making MMC available in South Africa was a good idea, with some recommending immediate introduction. Others felt that MMC should be introduced with caution. Various factors were recommended for consideration, including culture, the impact of circumcision on women, possible increase in sexual risk behaviour from behavioural disinhibition and that MMC may become another vertical health service programme. Most felt that MMC should be undertaken in neonates, however, acknowledged concerns about cultural responses to this. Recommendations on the implementation of MMC ranged from integrating services at primary health care level, to provision by private medical practitioners. In conclusion, MMC is viewed as a key HIV prevention strategy. However, there are numerous factors which could hinder introduction and uptake in South Africa and in the region. It is important to explore and understand these factors and for these to be aligned in the national MMC policy.

Assessing menopausal status in women aged 40 - 49 using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraception.

BACKGROUND: Determining symptoms of menopause in older users of hormonal injectable contraceptives may be challenging, owing to method-induced amenorrhoea, suppression of follicle-stimulating hormone (FSH) and vasomotor symptoms. OBJECTIVE: To investigate menopausal symptoms in women aged 40 - 49 using injectable contraceptives depot-medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN) or combined oral contraceptives (COCs), compared with non-users of hormonal contraception. METHODS: Women using DMPA (N = 127), NET-EN (N = 102), COCs (N = 106) and 161 non-hormonal contraceptive user controls were recruited. Baseline visit serum FSH was measured and information was collected on vasomotor symptoms and menstrual regularity. RESULTS: There was no difference in reporting of vasomotor symptoms between the groups. There was no evidence of a difference in FSH level between non-users (mean FSH 26.7 IU/ml, SD 28.7) and DMPA users (mean FSH 23.1 IU/ml, SD 27.8) (p = 0.64). However, the NET-EN (mean FSH 11.0 IU/ml, SD 10.9) (p = 0.003) and COC groups (mean FSH 12.5 IU/ml, SD 18.7) (p = 0.001) had significantly lower FSH levels compared with the non-user group. CONCLUSION: The lower FSH levels found in the NET-EN and COC users compared with controls may indicate a greater degree of suppression of FSH levels in these two methods, compared with DMPA. Measuring FSH levels may therefore be informative of menopausal status in DMPA users but not in NET-EN or COC users. Vasomotor symptoms may assist in assessing menopausal status in DMPA, NET-EN and COC users.

Prospective study of weight change in new adolescent users of DMPA, NET-EN, COCs, nonusers and discontinuers of hormonal contraception.

BACKGROUND: Weight gain is commonly reported as a side effect of hormonal contraception and can lead to method discontinuation or reluctance to initiate the method. The purpose of this study was to investigate weight change in adolescent (aged 15-19 years) users of depot-medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), combined oral contraceptives (COCs) and discontinuers of these methods as compared to nonusers of hormonal contraception. STUDY DESIGN: This longitudinal study recruited initiators of DMPA (n=115), NET-EN (n=115), COCs (n=116) and nonusers of contraception (n=144). Participants were followed up for 4-5 years, and details of current contraceptive method, including switching, discontinuing and/or starting hormonal methods were documented at each 6-monthly visit. Women were classified according to their contraceptive histories on completion of the study, and injectable users were combined into one group for analysis. Height, weight and self-reported dieting were recorded at each visit. RESULTS: There was no difference in mean age or weight between the groups at baseline. Women using DMPA or NET-EN throughout, or switching between the two, had gained an average of 6.2 kg compared to average increases of 2.3 kg in the COC group, 2.8 kg in nonusers and 2.8 kg among discontinued users of any method (p=.02). There was no evidence of a difference in weight gain between women classified as nonobese or classified as overweight/obese in any of the four study groups at baseline. CONCLUSION: There is fairly strong evidence that adolescent contraceptive hormonal injectable users appear to gain more weight than COC users, discontinuers and nonusers of contraception.

Bone mineral density in young women aged 19-24 after 4-5 years of exclusive and mixed use of hormonal contraception.

BACKGROUND: Use of depot-medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN) and low-dose combined oral contraceptives (COCs) has been associated with loss of bone mineral density (BMD) in adolescents. However, the effect of using a combination of these methods over time in this age group is limited. The aim of this cross-sectional study was to investigate BMD in young women (aged 19-24 years) with a history of mixed hormonal contraceptive use. STUDY DESIGN: BMD was measured at the spine, hip and femoral neck using dual X-ray absorptiometry. Women were classified into three groups: (1) injectable users (DMPA, NET-EN or both) (n=40), (2) mixed COC and injectable users (n=13) and (3) non-user control (n=41). RESULTS: Women in the injectables-only user group were found to have lower BMDs compared to the non-user group at all three sites, and there was evidence of a difference in BMD between these two groups at the spine after adjusting for body mass index (p=.042), hip (p=.025) and femoral neck (p=.023). The mixed COC/injectable user group BMD values were lower than those for controls; however, there was no evidence of a significant difference between this group and the non-user group at any of the three sites. CONCLUSION: This study suggests that BMD is lower in long-term injectable users but not when women have mixed injectable and COC use.

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.