Evidence map›Paper›PMID 39178280›Full record

Trial reportPloS one2024

The injectable contraceptives depot medroxyprogesterone acetate and norethisterone enanthate substantially and differentially decrease testosterone and sex hormone binding globulin levels: A secondary study from the WHICH randomized clinical trial.

Chanel Avenant, Mandisa Singata-Madliki, Alexis J Bick, Donita Africander, Yusentha Balakrishna, Karl-Heinz Storbeck, Johnson M Moliki, Sigcinile Dlamini, Salndave Skosana, Jenni Smit and 6 more

Abstract 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. 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

16 authors.

Chanel AvenantDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Mandisa Singata-MadlikiEffective Care Research Unit, Eastern Cape Department of Health/Universities of the Witwatersrand and Fort Hare, East London, South Africa.
Alexis J BickDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Donita AfricanderDepartment of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Yusentha BalakrishnaBiostatistics Research Unit, South African Medical Research Council, Durban, South Africa.
Karl-Heinz StorbeckDepartment of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.ORCID 0000-0003-1669-6383
Johnson M MolikiDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Sigcinile DlaminiDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
Salndave SkosanaDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, 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.
Ivana BeeshamWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa.
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.
George J HofmeyrEffective 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.ORCID 0000-0002-4414-4861

Funding

Combination treatment for protection against HIV1 and pregnancyR01HD083026 · NICHD · UNIVERSITY OF CAPE TOWN · PI HAPGOOD, JANET PATRICIA, HEL, ZDENEK · 2015 to 2019
$2.5M
Biological effects, hormone levels and mechanisms relevant to HIV-1 infection for women randomized to the injectable contraceptives depo-medroxyprogesterone acetate or norethisterone enanthate.R01AI152118 · NIAID · UNIVERSITY OF CAPE TOWN · PI CHEN, PAI-LIEN, HAPGOOD, JANET PATRICIA · 2020 to 2024
$2.3M
NIAID NIH HHS R01 AI152118NICHD NIH HHS R01 HD083026
6 · The paper itself

Abstract

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018-2019, randomized HIV-negative women aged 18-40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214-218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).

Indexed as

Contraceptive Agents, FemaleMedroxyprogesterone AcetateNorethindroneSex Hormone-Binding GlobulinTestosteroneAdolescentAdultFemaleHumansInjections, IntramuscularYoung AdultContraceptive Agents, FemaleMedroxyprogesterone AcetateNorethindronenorethindrone enanthateSex Hormone-Binding GlobulinTestosterone

Identifiers

PMID39178280
PMCPMC11343371

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Registered trials

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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.