Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries.

BACKGROUND: Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. METHODS: Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12-24 months after delivery (n = 1070). Women with a CD4 count of 200-500 cells/mm(3) and gestational age 28-36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm(3) initiated antiretroviral therapy, and >500 cells/mm(3) received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. RESULTS: At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥ 6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1-2 months of ARV's, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. CONCLUSIONS: Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring. TRIAL REGISTRATION NUMBER: ISRCTN71468401.

Sino-implant (II)--a levonorgestrel-releasing two-rod implant: systematic review of the randomized controlled trials.

BACKGROUND: Sino-implant (II) is a subdermal contraceptive implant manufactured in China. This two-rod levonorgestrel-releasing implant has the same amount of active ingredient (150 mg levonorgestrel) and mechanism of action as the widely available contraceptive implant Jadelle. We examined randomized controlled trials of Sino-implant (II) for effectiveness and side effects. STUDY DESIGN: We searched electronic databases for studies of Sino-implant (II) and then restricted our review to randomized controlled trials. The primary outcome of this review was pregnancy. RESULTS: Four randomized trials with a total of 15,943 women assigned to Sino-implant (II) had first-year probabilities of pregnancy ranging from 0.0% to 0.1%. Cumulative probabilities of pregnancy during the 4 years of the product's approved duration of use were 0.9% and 1.06% in the two trials that presented date for 4-year use. Five-year cumulative probabilities of pregnancy ranged from 0.7% to 2.1%. In one trial, the cumulative probability of pregnancy more than doubled during the fifth year (from 0.9% to 2.1%), which may be why the implant is approved for 4 years of use in China. Five-year cumulative probabilities of discontinuation due to menstrual problems ranged from 12.5% to 15.5% for Sino-implant (II). CONCLUSIONS: Sino-implant (II) is one of the most effective contraceptives available today. These available clinical data, combined with independent laboratory testing, and the knowledge that 7 million women have used this method since 1994, support the safety and effectiveness of Sino-implant (II). The lower cost of Sino-implant (II) compared with other subdermal implants could improve access to implants in resource-constrained settings.

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.

Prostate cancer and vasectomy: a hospital-based case-control study in China, Nepal and the Republic of Korea.

BACKGROUND: The study of a possible relationship between vasectomy and prostate cancer has yielded mixed results. Data from developing countries are limited. STUDY DESIGN: We conducted a hospital-based case-control study in China, Nepal and the Republic of Korea to evaluate the risk of prostate cancer after vasectomy. RESULTS: Prostate cancer in 294 cases (confirmed by independent pathologists) and 879 matched controls were included. The odds ratio of prostate cancer in men with a history of vasectomy was 1.21 [95% confidence interval (95% CI)=0.79, 1.87]. No significant trend was observed in risk by time since vasectomy or age at vasectomy. The odds ratio for localized disease was 1.02 (95% CI=0.53, 1.95); the odds ratio for later stages was 1.41 (95% CI=0.78, 2.53). No confounding factor was identified. The study illustrated differential misclassification of disease by vasectomy status; reference pathologists determined that 28% of men with a history of vasectomy, compared with 17% of men without a history of vasectomy, were misdiagnosed with prostate cancer by local pathologists. CONCLUSION: Vasectomy is not associated with an increased risk of prostate cancer in developing countries where the rate of the disease is low.

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.

Bone mineral density in women aged 40-49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception.

Most studies show that depot-medroxyprogesterone acetate (DMPA) has a negative effect on bone mass. There are conflicting reports with respect to recovery of bone mass with long-term use of DMPA. No 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 older women (40-49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study. One-hundred twenty-seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Bone mineral density was measured at the distal radius and midshaft of the ulna using dual X-ray absorptiometry. There was no significant difference in BMD between the four contraceptive user groups (p=.26) with and without adjustment for age. Although a small decrease in BMD was noted in the age range of 40-49 years, this was not statistically significant (p=.7). The BMD was found to be significantly associated with body mass index (BMI) (por=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). This study found no evidence that long-term use of DMPA, NET-EN and COCs affects BMD in this population.

The influence of economic development on the association between education and the risk of acute myocardial infarction and stroke.

Rates of myocardial infarction and stroke increase as countries "develop." These disorders emerge among higher socio-economic groups, but once "developed," most events occur in lower socio-economic groups. We evaluated the association between education as a measure of socio-economic status and risk of acute myocardial infarction (AMI) and stroke in regions at various stages of development and between stroke risk and life expectancy. The study comprised 2,478 cases of AMI or stroke and 6,819 controls among women aged 19-49, from Africa, Asia, Latin America, and Eastern Europe. Compared to those with high educational attainment, stroke risk was reduced among less educated women in Africa, but was significantly higher in the other three regions. Low education was associated with increased risk of AMI in Eastern Europe but not in the other three regions combined. Educationally related stroke risk was positively correlated with national life expectancy.