Evidence map›Paper›PMID 38530848›Full record

Trial reportPloS one2024

Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trial.

Mandisa Singata-Madliki, Jenni Smit, Mags Beksinska, Yusentha Balakrishna, Chanel Avenant, Ivana Beesham, Ishen Seocharan, Joanne Batting, Janet P Hapgood, G Justus Hofmeyr

Open access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Hormonal contraception for women at risk of HIV infection.The Cochrane database of systematic reviews · 2025
    Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Mandisa Singata-MadlikiEffective Care Research Unit, Eastern Cape Department of Health/Universities of the Witwatersrand and Fort Hare, East London, South Africa.
Jenni SmitWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa.
Mags BeksinskaWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa.
Yusentha BalakrishnaBiostatistics Research Unit, South African Medical Research Council, Durban, South Africa.ORCID 0000-0001-6449-3260
Chanel AvenantDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Ivana BeeshamWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa.ORCID 0000-0003-4889-8123
Ishen SeocharanBiostatistics Research Unit, South African Medical Research Council, Durban, South Africa.
Joanne BattingEffective Care Research Unit, Eastern Cape Department of Health/Universities of the Witwatersrand and Fort Hare, East London, South Africa.
Janet P HapgoodDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
G Justus HofmeyrEffective Care Research Unit, Eastern Cape Department of Health/Universities of the Witwatersrand and Fort Hare, East London, South Africa.
University of the Witwatersrand · ZAWestern Cape Department of Health · ZASouth African Medical Research Council · ZAUniversity of Cape Town · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObservational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels.

methodsThis open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18-40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W).

resultsAt 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured.

conclusionsEstradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question.

trial registrationPACTR 202009758229976.

Indexed as

Contraceptive Agents, FemaleHIV InfectionsContraceptionEstradiolFemaleHumansMedroxyprogesterone AcetateNorethindroneContraceptive Agents, FemaleEstradiolMedroxyprogesterone AcetateNorethindronenorethindrone enanthate

Identifiers

PMID38530848
PMCPMC10965066
OpenAlexW4393188047

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.