Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

Renee Heffron¹, Sharon L Achilles², Laneta J Dorflinger³, Janet P Hapgood⁴, James Kiarie⁵, Chelsea B Polis⁶, Petrus S Steyn⁷

Affiliations

¹ Department of Global Health, University of Washington, 325 Ninth Avenue Box 359927, Seattle, WA, USA; Department of Epidemiology, University of Washington, 325 Ninth Avenue Box 359927, Seattle, WA, USA. Electronic address: rheffron@uw.edu.
² Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Family Planning Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA. Electronic address: achisx@upmc.edu.
³ FHI 360, 359 Blackwell Street, Suite 200, Durham, NC, USA 27701. Electronic address: ldorflinger@fhi360.org.
⁴ Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Private Bag X3, Rondebosch, 7701, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Private Bag X3, Rondebosch, 7701, Cape Town, South Africa. Electronic address: Janet.Hapgood@uct.ac.za.
⁵ Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland. Electronic address: kiariej@who.int.
⁶ Guttmacher Institute, 125 Maiden Lane, 7th Floor, Manhattan, New York, 10038, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD 21205, USA. Electronic address: cpolis@guttmacher.org.
⁷ Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland. Electronic address: steynp@who.int.

PMID: 30576636
PMCID: PMC6467541
DOI: 10.1016/j.contraception.2018.12.001

Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

Renee Heffron et al. Contraception. 2019 Apr.

. 2019 Apr;99(4):199-204.

doi: 10.1016/j.contraception.2018.12.001. Epub 2018 Dec 18.

Authors

Renee Heffron¹, Sharon L Achilles², Laneta J Dorflinger³, Janet P Hapgood⁴, James Kiarie⁵, Chelsea B Polis⁶, Petrus S Steyn⁷

Affiliations

¹ Department of Global Health, University of Washington, 325 Ninth Avenue Box 359927, Seattle, WA, USA; Department of Epidemiology, University of Washington, 325 Ninth Avenue Box 359927, Seattle, WA, USA. Electronic address: rheffron@uw.edu.
² Department of Obstetrics, Gynecology, and Reproductive Sciences and Center for Family Planning Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA. Electronic address: achisx@upmc.edu.
³ FHI 360, 359 Blackwell Street, Suite 200, Durham, NC, USA 27701. Electronic address: ldorflinger@fhi360.org.
⁴ Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Private Bag X3, Rondebosch, 7701, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Private Bag X3, Rondebosch, 7701, Cape Town, South Africa. Electronic address: Janet.Hapgood@uct.ac.za.
⁵ Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland. Electronic address: kiariej@who.int.
⁶ Guttmacher Institute, 125 Maiden Lane, 7th Floor, Manhattan, New York, 10038, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD 21205, USA. Electronic address: cpolis@guttmacher.org.
⁷ Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland. Electronic address: steynp@who.int.

PMID: 30576636
PMCID: PMC6467541
DOI: 10.1016/j.contraception.2018.12.001

Erratum in

Corrigendum to "Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women" [Contraception 99 (2019) 199-204].
Heffron R, Achilles SL, Dorflinger LJ, Hapgood JP, Kiarie J, Polis CB, Steyn PS. Heffron R, et al. Contraception. 2019 Jul;100(1):88. doi: 10.1016/j.contraception.2019.05.014. Contraception. 2019. PMID: 31229224 Free PMC article. No abstract available.

Abstract

Access to safe and effective contraceptive choices is a reproductive right and contributes tremendously to improvements in maternal and child health. Progestin-only injectables, particularly intramuscularly injected depot medroxyprogesterone acetate (DMPA-IM), have received increased attention given findings suggesting a potential association with increased HIV risk. For women at high risk of HIV, the World Health Organization's Medical eligibility criteria for contraceptive use currently aggregate recommendations for all progestin-only injectables, including DMPA-IM, subcutaneously injected DMPA (DMPA-SC) and intramuscularly injected norethindrone/ norethisterone enanthate (NET-EN), except in the case of some drug interactions. We considered whether published data indicate differences or similarities between these injectables relevant to risk of acquiring HIV. In vitro data confirm different biological activities of these distinct progestins, including that MPA, and not NET, binds and activates the glucocorticoid receptor resulting in different biological effects relevant to immune function. Limited clinical data suggest changes in immunologic activity following DMPA-IM and NET-EN initiation, but interstudy variation and study design differences diminish ability to determine clinical relevance and the degree to which DMPA-IM and NET-EN could act differentially. The highest-quality epidemiologic studies suggest a potential 40% increase in HIV incidence in users of DMPA-IM relative to women not using hormonal contraception but no significant increase in risk in users of NET-EN. In our opinion, most of the available biologic activity and epidemiologic data indicate that DMPA and NET-EN are likely to act differently, and data remain too limited to evaluate differences between DMPA-IM and DMPA-SC.

Keywords: Contraception; DMPA; HIV; NET-EN; Progestin.

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References

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1. Pfizer . 2010. Prescribing information for DEPO-PROVERA CI (medroxyprogesterone acetate) injectable suspension, for intramuscular use. Accessed 15 May 2018. [Last revision]
1. Bayer P.L.C. 2017. Product information for Noristerat 200mg, solution for intramuscular injection. Accessed 15 May 2018. [Last update]
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Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

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Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

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