Medroxyprogesterone Acetate

Participants received an injection of 150 mg/mL DMPA-IM (Depo Provera; Pfizer, Puurs, Belgium), which was provided on site at enrolment and then every 3 months until the final follow-up visit at 18 months after enrolment, a copper IUD (Optima TCu380A; Injeflex, Sao Paolo, Brazil) at enrolment, or a LNG implant (Jadelle; Bayer, Turku, Finland) at enrolment. Placement was confirmed for the LNG implant at every visit and for the copper IUD at 1 month, the final visit, and when clinically indicated. Women returned for scheduled follow-up visits at 1 month after enrolment to address initial contraceptive side-effects and every 3 months to 18 months for visits that included HIV serological testing, contraceptive counselling, and safety monitoring (appendix pp 14–17). Behavioural assessment was done at 3-month visits with standardised questionnaires in face-to-face interviews. At baseline, we tested for sexually transmitted infections (STIs; Chlamydia trachomatis, Neisseria gonorrhoeae, and HSV-2) and provided treatment for curable STIs using both syndromic and aetiological diagnoses. During follow-up, we provided syndromic STI management. We tested for pregnancy at enrolment, the final study visit, and when clinically indicated; women who became pregnant continued trial follow-up and were referred for further management. Women were asked about adverse events at every visit, including serious adverse events; we included hospital admissions due to pregnancy and delivery among serious adverse events. Women were counselled that they could at any time choose to discontinue the method to which they were randomly assigned and instead choose another trial method, a contraceptive method not being assessed in this trial, or no method; women who discontinued their randomly assigned method were retained in the trial. Building off various sources,12 , 13 , 14 , 15 , 16 we developed trial-specific contraceptive method-related counselling materials, which included the informed consent document, method-specific information sheets, a pre-randomisation flip chart, and a post-randomisation flip chart.
At every visit, participants received a comprehensive package of HIV prevention services, including HIV risk reduction counselling, participant and partner HIV and STI testing and management, condoms, and, as it became a part of national standard of prevention, pre-exposure prophylaxis (PrEP). Counselling messages related to HIV risk, including PrEP and condom use, were designed and implemented consistently across the three groups throughout the trial. Women who acquired HIV were linked to HIV care and treatment. In March, 2017, when WHO released guidance related to the use of progestin-only contraceptives by women at high risk of HIV infection, and the WHO Medical Eligibility Criteria for DMPA-IM changed from a category 1 (“a condition for which there is no restriction for the use of the contraceptive method”) to a category 2 (“a condition where the advantages of using the method generally outweigh the theoretical or proven risks”),¹⁷ all participants were provided with this updated information across all three groups. Site teams consistently counselled participants that none of the three contraceptive methods being used in the study provided protection against HIV or other STIs and advised women to always use condoms in addition to their contraceptive method. The study team made concerted efforts to not provide additional or differential information or counselling to women in the DMPA-IM group.
After enrolment was completed, we tested baseline serum samples from a randomly selected subset of the trial population (60 per site, 20 from each group) for medroxyprogesterone acetate using a validated, high-performance liquid chromatography–heated electrospray ionisation–tandem triple quadrupole mass spectrometry assay¹⁸ (link) to understand the frequency of DMPA-IM use before randomisation (concentrations of more than 0·4 ng/mL were used to define likely use within the previous 6 months [appendix pp 25–26]) and to explore the accuracy of self-report for the trial eligibility exclusion criterion for use during that same time period.

Participants were recruited from onchocerciasis endemic villages between 0°30′ and 0°45′E, 6°45′ and 7°0′N within the River Tordzi basin in the Volta Region of South-eastern Ghana. The vast majority (90%) of participants came from the villages Honuta-Gbogame, Kpedze-Anoe, Togorme, Aflakpe, Luvudo, Kpoeta-Ashanti and Hoe, the remainder from 11 other villages in the area (Figure 3). This area was not included in vector control activities under the Onchocerciasis Control Programme because at the time of the OCP it was forested. Simuliid species were Simulium yahense and Simulium squamosum[33] (link). At the time of this study, the area was not yet included in the ivermectin mass distribution programme of the National Onchocerciasis Control Programme because it is overall hypoendemic with small meso- or hyperendemic foci. The area is not endemic for lymphatic filariasis or loiasis.
A total of 172 of 196 planned individuals meeting the intensity of infection criteria described above but otherwise regarded as healthy based on physical examination, electrocardiography, medical and medication history, serum biochemistry, haematology and semiquantitative urinalysis participated in the study. Volunteers with a history of or current neurological or neuropsychiatric disease or epilepsy, orthostatic hypotension at screening, hyperreactive onchodermatitis and antifilarial therapy within the previous 5 years as well as pregnant and breastfeeding women were excluded. Women of child-bearing potential who wanted to participate had to agree to contraception (depo-medroxyprogesterone acetate or levonorgestrel implants) during the first 150 days after treatment. The pre-treatment evaluations included those detailed in the footnote to Table 1 and height measurement. Vital signs were obtained 12 times during the pre-treatment evaluations and the mean was used to assess changes post-treatment.

A vet-Dop2 Doppler blood-pressure system with a sphygmomanometer and an animal blood-pressure cuff of the correct size was used to measure systolic blood pressure [46 (link)]. Initial BP values of rats were recorded and, thereafter, hypertension was induced by subcutaneous injection of Medroxy Progesterone Acetate (MPA, 10 mg/kg/week) for 2 weeks. Animals with a minimum mean BP of 167 ± 3.2 mmHg were considered hypertensive. To test the effect of treatments on hypertension, animals were assigned to five groups (n = 6). Group I was normal controls, Group II was positive controls, Group III was treated with TEL (5 mg/kg orally), Group IV received optimized beads without oil entrapment, and Group V received oil-entrapped optimized beads. The standard and the formulation were administered through oral gavage through suspension in sodium CMC for 21 days, BP was measured at 1, 2, 3, 4, 5, 6, 7, 8, 10, and 12 h following treatment.