Plasma levels of medroxyprogesterone acetate (MPA), estradiol and progesterone in the rhesus monkey after intramuscular administration of depo-provera®

Mora, Gabriel; Johansson, Elof D. B.

doi:10.1016/0010-7824(76)90101-3

Cited by 9 publications

(8 citation statements)

References 14 publications

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Section: Introductionmentioning

confidence: 88%

“…Macaques, however, metabolize DMPA faster than women 15 . In particular, after intramuscular DMPA injection of comparable doses in macaques, MPA appearance in blood peaks faster and at higher levels than in humans, but it also declines faster and disappears within one month, while it remains detectable for much longer in humans 15 . In earlier work by us and our colleagues 16-18 , various DMPA doses were tested in pigtail macaques (1, 3, 15, 30 mg per macaque, and 0.5, 1.5, and 2.5 mg/kg of body weight).…”

Section: Introductionmentioning

confidence: 88%

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A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk

Butler

Ritter

Ellis

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Introduction Hormonal contraception with DMPA may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. Here we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on SHIV acquisition risk in pigtail macaques (Macaca nemestrina). Methods Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5 mg/kg DMPA monthly, while eleven were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 sub-optimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. Results It took a median 5.5 viral challenges to infect DMPA-treated macaques, and 9 challenges for controls (p=0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI 0.6 – 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA-treatment in all animals (mean 30 and 219 micrometers in DMPA-treated and control macaques, respectively, p=0.03, t-test using the Satterthwaite degrees-of-freedom approximation). Conclusions SHIV infections in DMPA treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on SIV or SHIV acquisition.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 88%

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk

Butler

Ritter

Ellis

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Each animal was given an intramuscular (IM) DMPA injection of Pfizer's Depo‐Provera ® (Pfizer, New York, NY, USA) into the gluteal muscle. It is known that macaques metabolize DMPA faster than women , who receive an intramuscular injection of 150 mg of DMPA (Depo‐Provera ® ) every 3 months for effective suppression of ovulation and contraception. This increased metabolism necessitates more frequent drug administration in macaques than in women.…”

Section: Methodsmentioning

confidence: 99%

Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques

Butler

Ritter

Ellis

et al. 2015

J of Medical Primatology

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“…Further complicating the interpretation of experimental data obtained in animal models is the possibility that substantial differences may exist between humans and nonhuman primates in the pharmacokinetics and pharmacodynamics of MPA and other hormones ( 134 , 171 , 248 ). Further studies are required to establish this, given the difficulty in comparing nonequivalent doses between humans and monkeys in nonparallel studies ( 248 ), the large degree of variation in reported MPA serum concentrations between studies and individuals on DMPA-IM in humans, as well as the variation in apparent half-life values for the latter due to different sampling times for the establishment of C max ( 46 , 74 ). Using similar doses per kilogram of body weight in monkeys and humans may not result in comparable serum levels because metabolism may vary between species ( 248 ).…”

Section: Animal Studies Addressing the Effect Of Hc On The Acquisitiomentioning

confidence: 99%

“…Further studies are required to establish this, given the difficulty in comparing nonequivalent doses between humans and monkeys in nonparallel studies ( 248 ), the large degree of variation in reported MPA serum concentrations between studies and individuals on DMPA-IM in humans, as well as the variation in apparent half-life values for the latter due to different sampling times for the establishment of C max ( 46 , 74 ). Using similar doses per kilogram of body weight in monkeys and humans may not result in comparable serum levels because metabolism may vary between species ( 248 ). Two studies have investigated the effects of equivalent doses in monkeys compared with women.…”

Section: Animal Studies Addressing the Effect Of Hc On The Acquisitiomentioning

confidence: 99%

Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms

2018

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Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are rather limited in settings with restricted economic resources that frequently overlap with areas of high HIV-1 prevalence. The predominant contraceptive used in sub-Saharan Africa is the progestin-only three-monthly injectable depot medroxyprogesterone acetate. Determination of whether HCs affect HIV-1 acquisition has been hampered by behavioral differences potentially confounding clinical observational data. Meta-analysis of these studies shows a significant association between depot medroxyprogesterone acetate use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate, although data for norethisterone enanthate are limited. Susceptibility to HIV-1 and other sexually transmitted infections may, however, be dependent on the type of progestin present in the formulation. Several underlying biological mechanisms that may mediate the effect of HCs on HIV-1 and other sexually transmitted infection acquisition have been identified in clinical, animal, and ex vivo studies. A substantial gap exists in the translation of basic research into clinical practice and public health policy. To bridge this gap, we review the current knowledge of underlying mechanisms and biological effects of commonly used progestins. The review sheds light on issues critical for an informed choice of progestins for the identification of safe, effective, acceptable, and affordable contraceptive methods.

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Plasma levels of medroxyprogesterone acetate (MPA), estradiol and progesterone in the rhesus monkey after intramuscular administration of depo-provera®

Cited by 9 publications

References 14 publications

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk

A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk

Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques

Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms

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