Pregnenolone Neurosteroid for the Remedy of Menopausal Melancholy

Over the previous couple of years we’ve got heard an excellent deal about neurosteroids, also called neuroactive steroids.  This class of compounds are steroid hormones produced within the mind and endocrine tissues which might modulate neurotransmission.  Animal research have demonstrated that neurosteroids have a broad vary of actions, together with antidepressant, anxiolytic, sedative, analgesic, anticonvulsant, neuroprotective, and neuroproliferative results.  

Whereas we’ve got recognized about neuroactive results of steroids for the reason that 1940s, it has been troublesome to copy the helpful results of naturally produced neurosteroids with related compounds synthesized within the laboratory.  A number of completely different neurosteroids have been examined as anticonvulsants and anaesthetic brokers; nonetheless, we’ve got seen probably the most  sturdy medical findings with a number of completely different derivatives of allopregnanolone used as antidepressants.   Certainly one of these allopregnanolone analogues, brexanolone, was accepted final yr by the FDA for the remedy of extreme postpartum melancholy and is now being marketed as Zulresso (Sage Therapeutics).

Allopregnanolone is produced by the human physique as a byproduct of progesterone.  Some have speculated that shifting ranges of allopregnanolone could play a task within the pathophysiology of reproductive hormone-associated temper problems, together with premenstrual dysphoric dysfunction (PMDD) and menopausal melancholy.  Given the constructive outcomes of brexanolone for postpartum melancholy, there was appreciable curiosity in exploring the effectiveness of comparable neurosteroids in ladies with different kinds of reproductive hormone-associated temper problems.  

In a brand new examine, Dr. Marlene Freeman and colleagues on the Middle for Ladies’s Psychological Well being will examine the effectiveness of pregnenolone, a neurosteroid which is a spinoff of progesterone, for the remedy of melancholy in the course of the menopausal transition.  Pregnenolone is produced within the physique and is concerned within the synthesis and metabolism of different steroid hormones, together with progestogens and estrogens.  Pregnenolone is biologically energetic and modulates numerous neurotransmitter techniques, together with the endocannabinoid system. Its metabolite pregnenolone sulfate is just like brexanolone and acts as a unfavorable allosteric modulator of the GABA-A receptor and can be a constructive allosteric modulator of the NMDA receptor.

Each preclinical and human knowledge counsel that pregnenolone could also be a promising remedy for melancholy. Dr. Freeman’s examine will check the effectiveness of pregnenolone in ladies with menopausal melancholy.  

Eligibility: This examine is recruiting ladies between the ages of 40 and 67 who’re perimenopausal (adjustments in menstrual cycle and/or bodily signs of menopause) OR early postmenopausal (inside 5 years of the final menstrual interval).

Research Participation: Contributors will probably be randomized into certainly one of two remedy teams (placebo or pregnenolone) and will probably be requested to finish questionnaires about temper, cognitive perform, demographic and medical historical past, psychiatric historical past, and menopausal signs.  All evaluations and drugs included as a part of this examine could be supplied without charge.  

Time Dedication: 16 weeks with three in-person visits at MGH and 6 digital visits. 

Compensation: As much as $390 for taking part within the 16-week examine.

For data, you possibly can contact Lauren at [email protected].  It’s also possible to learn extra about this examine HERE.

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