Over the previous couple of years now we have heard an important deal about neurosteroids, also referred to as 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 now we have identified about neuroactive results of steroids because the Forties, it has been troublesome to copy the useful results of naturally produced neurosteroids with comparable compounds synthesized within the laboratory. A number of completely different neurosteroids have been examined as anticonvulsants and anaesthetic brokers; nevertheless, now we have seen essentially the most strong scientific findings with a number of completely different derivatives of allopregnanolone used as antidepressants. One in every of these allopregnanolone analogues, brexanolone, was permitted final 12 months by the FDA for the therapy 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 job within the pathophysiology of reproductive hormone-associated temper problems, together with premenstrual dysphoric dysfunction (PMDD) and menopausal melancholy. Given the optimistic outcomes of brexanolone for postpartum melancholy, there was appreciable curiosity in exploring the effectiveness of comparable neurosteroids in girls with different kinds of reproductive hormone-associated temper problems.
In a brand new research, Dr. Marlene Freeman and colleagues on the Middle for Girls’s Psychological Well being will examine the effectiveness of pregnenolone, a neurosteroid which is a by-product of progesterone, for the therapy 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 lively and modulates varied neurotransmitter programs, together with the endocannabinoid system. Its metabolite pregnenolone sulfate is much like brexanolone and acts as a unfavorable allosteric modulator of the GABA-A receptor and can also be a optimistic allosteric modulator of the NMDA receptor.
Each preclinical and human information recommend that pregnenolone could also be a promising therapy for melancholy. Dr. Freeman’s research will check the effectiveness of pregnenolone in girls with menopausal melancholy.
Eligibility: This research is recruiting girls between the ages of 40 and 67 who’re perimenopausal (modifications in menstrual cycle and/or bodily signs of menopause) OR early postmenopausal (inside 5 years of the final menstrual interval).
Examine Participation: Individuals can be randomized into one among two therapy teams (placebo or pregnenolone) and can 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 research could be offered without charge.
Time Dedication: 16 weeks with 3 in-person visits at MGH and 6 digital visits.
Compensation: As much as $390 for collaborating within the 16-week research.
For data, you’ll be able to contact Lauren at LKOBYLSKI@mgh.harvard.edu. You may also learn extra about this research HERE.