Evidence map›Paper›PMID 41489365›Full record

Trial reportBiology of reproduction2026

Injectable contraceptives differentially affect the hypothalamic-pituitary-gonadal axis and amenorrhea incidence†.

Alexis J Bick, Chanel Avenant, Carole-Keza Capitaine, Sharoné van Eck, Mu-Tien Lee, Johnson M Moliki, Sigcinile Dlamini, David W Erikson, Jenni Smit, Mags Beksinska and 4 more

Erratum issuedAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Biology of reproduction, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Alexis J BickDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0002-9219-7255
Chanel AvenantDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0002-2114-1473
Carole-Keza CapitaineDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0001-9385-343X
Sharoné van EckDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0001-9093-615X
Mu-Tien LeeFamily Health International (FHI) 360, Durham, North Carolina, USA.ORCID 0009-0001-8855-5769
Johnson M MolikiDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0009-0006-0675-4606
Sigcinile DlaminiDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0003-0733-6837
David W EriksonEndocrine Technologies Core, Oregon National Primate Research Center, Beaverton, Oregon, USA.ORCID 0000-0002-3383-9297
Jenni SmitWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, Kwa-Zulu Natal, South Africa.ORCID 0000-0002-5337-5995
Mags BeksinskaWits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, Kwa-Zulu Natal, South Africa.ORCID 0000-0002-4169-4112
G Justus HofmeyrEffective Care Research Unit, Eastern Cape Department of Health / University of the Witwatersrand and Walter Sisulu University, East London, Eastern Cape, South Africa.ORCID 0000-0002-3080-1007
Donita J AfricanderDepartment of Biochemistry, Stellenbosch University, Stellenbosch, Western Cape, South Africa.ORCID 0000-0002-3429-7100
Pai-Lien ChenFamily Health International (FHI) 360, Durham, North Carolina, USA.ORCID 0000-0001-8910-5316
Janet P HapgoodDepartment of Molecular and Cell Biology, University of Cape Town, Cape Town, Western Cape, South Africa.ORCID 0000-0002-4414-4861

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
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 HD083026NIH HHS P51 OD011092
6 · The paper itself

Abstract

Hormonal contraceptives modulate the hypothalamic-pituitary-ovarian (HPO) axis; however, underlying mechanisms and differences between contraceptives are underexplored. The Women's Health Injectable Contraception and HIV trial randomised 521 women to intramuscular depot medroxyprogesterone acetate (DMPA-IM) or norethisterone enanthate (NET-EN) and showed similar decreased estradiol levels, but more amenorrhea for DMPA-IM users. This secondary study excluded for misreporting contraceptive use for 128 participants (DMPA-IM n = 65; NET-EN n = 63). Peripheral blood serum collected at initiation and one week after the 24-week injection (25 W), at peak progestin levels, was analysed for gonadal steroids, progestins and peptide hormones. While no changes were detected in peripheral gonadotropin-releasing hormone levels, DMPA-IM decreased luteinising hormone (LH) less than NET-EN. DMPA-IM increased, while NET-EN decreased follicle-stimulating hormone (FSH). Both contraceptives substantially decreased gonadal steroid levels, more so in NET-EN users for testosterone and estradiol. Post-menopausal-like hypoestrogenic effects were greater than previously reported, consistent with the substantial reduction in LH levels. Whether reduced LH levels are due to direct pituitary, hypothalamic, or supra-hypothalamic effects by progestins, is unclear. MPA, unlike NET, increased fsh expression in LβT2 cells, likely via the glucocorticoid receptor, consistent with direct effects on the pituitary by MPA in women. Amenorrhea associated in a time-varying manner with MPA and HPO hormone levels and LH/FSH, for DMPA-IM but not NET-EN users. HPO hormone profiles differ between DMPA-IM and NET-EN users and compared to pre- and post-menopausal women. Mechanisms affecting amenorrhea likely differ between contraceptives, with lower 25 W LH/FSH being consistent with more amenorrhea for DMPA-IM.

Indexed as

AmenorrheaContraceptive Agents, FemaleHypothalamo-Hypophyseal SystemMedroxyprogesterone AcetateNorethindroneOvaryAdolescentAdultFemaleHumansHypothalamic-Pituitary-Gonadal AxisInjections, IntramuscularYoung AdultContraceptive Agents, FemaleMedroxyprogesterone AcetateNorethindronenorethindrone enanthateamenorrheagonadotropin-releasing hormonegonadotropinshypothalamic–pituitary-ovarian axismedroxyprogesterone acetatenorethisteroneovarian steroids

Identifiers

PMID41489365
PMCPMC12958466

What OpenQuestion holds

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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.