The other side of progestins: effects in the brain

Abstract

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.

Medroxyprogesterone Acetate Impairs Amyloid Beta Degradation in a Matrix Metalloproteinase-9 Dependent Manner

“…We also raise awareness for the unmet need for in vivo investigation for the potential cognitive and pathological outcomes of MPA. There is currently an abundance of literature which focuses on the effects of estrogen, estradiol, testosterone, and progesterone on the brain, and particularly amyloid-beta production and clearance (Vest and Pike, 2013;Li and Singh, 2014;Giatti et al, 2016;Uchoa et al, 2016). There is still a paucity of published research addressing the potential effects of progestins, more specifically MPA, on the brain.…”

Neuroactive Steroids in First-Episode Psychosis: A Role for Progesterone?

“…Conversely, preclinical evidence showed that the administration of exogenous PROG could exert antipsychotic-like effects [ 14 , 15 ]. Lastly, recent evidence suggests that antipsychotics benefits might depend on their anti-inflammatory role [ 39 ]: interestingly, progesterone may share similar properties [ 40 ]. Further research should clarify the status of PROG in psychotic disorders, with the ultimate aim of possible therapeutical applications [ 13 ].…”

Happy with the method? : Sexual function changes in young women using contraception

“…Dosage, bioavailability, protein binding, receptor binding affinity, different metabolites and multiple receptors and signalling pathways, and differing inter-individual variability make the available research results difficult to extrapolate into clinically relevant information for progestogens in general. (49) Some studies have shown that the biologically active progestogen, progesterone, has a negative effect on sexual desire and sex drive. (38,50) However, the progesterone level fluctuates over the menstrual cycle whereas all HC use implies a more continuous level of progestogen over time.…”