Pregnenolone Neurosteroid for menopausal depression

Over the past few years, we’ve heard a lot about neurosteroids, also known as neuroactive steroids. Compounds in this class are steroid hormones produced in the brain and endocrine tissues that can modulate neurotransmission. Animal studies have shown that neurosteroids have a wide range of actions, including antidepressant, anxiolytic, sedative, analgesic, anticonvulsant, neuroprotective, and neuroproliferative effects.

Although we have known about the neuroactive effects of steroids since the 1940s, it has been difficult to replicate the beneficial effects of naturally produced neurosteroids with similar compounds synthesized in the laboratory. Several different neurosteroids have been tested as anticonvulsants and anesthetics; However, we have seen the strongest clinical findings with several different allopregnanolone derivatives used as antidepressants. One of these allopregnanolone analogs was brexanolone It was approved by the FDA last year for the treatment of severe postpartum depression and is now sold as Zulresso (Sage Therapeutics).

Allopregnanolone is produced by the human body as a byproduct of progesterone. Some have suggested that altered allopregnanolone levels may play a role in the pathophysiology of reproductive hormone-related mood disorders, including premenstrual dysphoric disorder (PMDD) and menopausal depression. Given the positive results of brexanolone for postpartum depression, there has been considerable interest in investigating the efficacy of similar neurosteroids in women with other types of reproductive hormone-related mood disorders.

In an ongoing study, Dr. Marlene Freeman Associates and colleagues at the Center for Women’s Mental Health are investigating the efficacy of pregnenolone, a neurosteroid derivative of progesterone, for the treatment of depression during the menopausal transition. Pregnenolone is produced in the body and is involved in the synthesis and metabolism of other steroid hormones, including progestogens and estrogens. Pregnenolone is biologically active and modulates various neurotransmitter systems, including the endocannabinoid system. Its metabolite pregnenolone sulfate is similar to brexanolone and acts as a negative allosteric modulator of the GABA-A receptor and is also a positive allosteric modulator of the NMDA receptor.

Both preclinical and human data suggest that pregnenolone may be a promising treatment for depression. Dr. Freeman’s study will test the effectiveness of pregnenolone in women with menopausal depression.

Compliance. This study is enrolling women aged 40 to 67 who are in menopause (menstrual cycle changes and/or physical symptoms of menopause) OR early postmenopausal (within 5 years of last menstrual period).

Participation in the study. Participants will be randomized to one of two treatment groups (placebo or pregnenolone) and asked to complete questionnaires on mood, cognitive function, demographic and medical history, psychiatric history, and menopausal symptoms. All assessments and medications included as part of this study will be provided free of charge.

Term obligation. 16 weeks with 3 in-person visits to MGH and 6 virtual visits.

Compensation. Up to $650 to participate in a 16-week study.

For information, you can contact Ellen at You can also read more about this study HERE.

Source link