Reprint of “Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe?”

Stanczyk, Frank Z.; Bhavnani, Bhagu R.

doi:10.1016/j.jsbmb.2015.08.013

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…WHI results reported an increased risk for breast cancer, coronary heart disease, stroke, and pulmonary embolism in the CEE + MPA arm of the study (Rossouw et al 2002). In addition, many studies report conflicting results of PROG vs MPA administration in different animal models and HRT patients , Stanczyk & Bhavnani 2015. Observations so far obtained suggest that, even if PROG and MPA are nearly identical in preventing the uterotrophic effects of unopposed estrogen treatment, they are profoundly different in their mechanism of action on brain.…”

Section: Protective Effects Of Progestins In the Brainmentioning

confidence: 99%

“…Many neuroprotective effects of PROG seem to be mediated by its conversion into neuroactive metabolites, such as DHP and allopregnanolone (Melcangi et al 2014. Interestingly, it has been reported that MPA could antagonize the conversion of PROG into allopregnanolone, through the inhibition of ARK1C ezyme (Khanim et al 2014), possibly blocking progesterone neuroprotective effects (Stanczyk & Bhavnani 2015).…”

Section: Protective Effects Of Progestins In the Brainmentioning

confidence: 99%

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The other side of progestins: effects in the brain

Giatti

Melcangi

Pesaresi

2016

Journal of Molecular Endocrinology

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Progestins are a broad class of progestational agents widely differing in their chemical structures and pharmacological properties. Despite emerging data suggest that progestins, besides their action as endometrial protection, can also have multiple nonreproductive functions, much remains to be discovered regarding the actions exerted by these molecules in the nervous system. Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. This is extremely interesting, since some of the progestins currently used in clinical practice exert neuroprotective and anti-inflammatory effects in the nervous system, opening new promising opportunities for the use of these molecules as therapeutic agents for trauma and neurodegenerative disorders.

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Section: Protective Effects Of Progestins In the Brainmentioning

confidence: 99%

Section: Protective Effects Of Progestins In the Brainmentioning

confidence: 99%

The other side of progestins: effects in the brain

Giatti

Melcangi

Pesaresi

2016

Journal of Molecular Endocrinology

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“…Medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) are two common synthetic progestogens ( Figure 1). Although, by design, MPA and LNG have slightly improved PK profiles compared to progesterone, they still individual variability in plasma concentrations, and undergo substantial first-pass metabolism by cytochrome P450 (CYP450) enzymes [5][6][7]. Though CYP450 metabolism is commonly described as occurring in the liver, these enzymes are also highly expressed in mature enterocytes of the gut wall [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) are two common synthetic progestogens ( Figure 1 ). Although, by design, MPA and LNG have slightly improved PK profiles compared to progesterone, they still commonly cause GI side effects, show significant inter-individual variability in plasma concentrations, and undergo substantial first-pass metabolism by cytochrome P450 (CYP450) enzymes [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

et al. 2020

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Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.

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