The transition to menopause, or perimenopause, represents the passage from reproductive to non-reproductive life. Throughout the perimenopause, girls expertise irregular menstrual cycles, which replicate the big fluctuations in ovarian hormone secretion throughout this time. As well as, girls could expertise vasomotor signs, altered sleep patterns, modifications in cognition, and melancholy. Whereas hormone alternative remedy (HRT) has been used to handle bodily signs related to the menopausal melancholy, a lot much less consideration has been centered on the remedy of menopausal melancholy. Considerations concerning the long-term use of HRT have restricted its use, and girls experiencing melancholy on this setting usually use conventional antidepressants, mostly serotonergic reuptake inhibitors. Whereas these antidepressants do work for a lot of girls, there’s a clear have to develop different interventions for girls who can not take or don’t reply to serotonergic antidepressants.
Over the previous couple of years now we have heard an amazing 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 in regards to the neuroactive results of steroids for the reason that Forties, it has been troublesome to duplicate the useful results of naturally produced neurosteroids with comparable compounds synthesized within the laboratory. There has not too long ago been some progress, and a number of other completely different neurosteroids have been examined as anticonvulsants and anesthetic brokers; nonetheless, now we have seen essentially the most strong scientific findings with a number of completely different derivatives of allopregnanolone used as antidepressants. Considered one of these allopregnanolone analogues, brexanolone, was accredited by the FDA for the remedy of extreme postpartum melancholy and is now being marketed as Zulresso (Sage Therapeutics). One other allopregnanolone by-product, zuranolone, has additionally been proven to be efficient for postpartum melancholy.
Given the efficacy of those neurosteroid brokers for the remedy of postpartum melancholy, many have speculated that derivatives of allopregnanolone could also be efficient for the remedy of different reproductive hormone-associated temper problems, together with premenstrual dysphoric dysfunction (PMDD) and menopausal melancholy. Allopregnanolone is produced by the human physique as a byproduct of progesterone. Whereas most earlier analysis has centered on the mood-modulating results of estrogen and have speculated that falling ranges of estrogen set off depressive signs in some girls, different research have urged 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. In mild of the constructive outcomes of brexanolone for postpartum melancholy, there was appreciable curiosity in exploring the effectiveness of comparable neurosteroids in girls with different sorts of reproductive hormone-associated temper problems.
In a brand new examine, Dr. Marlene Freeman and colleagues on the Middle for Girls’s Psychological Well being is at present investigating the effectiveness of pregnenolone, one other neurosteroid which is a by-product 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 methods, together with the endocannabinoid system. Its metabolite pregnenolone sulfate is just like brexanolone and acts as a adverse allosteric modulator of the GABA-A receptor and can also be a constructive allosteric modulator of the NMDA receptor.
Each preclinical and human information recommend that pregnenolone could also be a promising remedy for melancholy. Dr. Freeman’s examine will take a look at the effectiveness of pregnenolone in girls with menopausal melancholy.
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For data, you may contact Ella at erossa@mgh.harvard.edu. You may also learn extra about this examine HERE.
