Progesterone loading as a strategy for treating postpartum depression

Abstract

Postpartum depression (PPD) is a severe disorder that adversely impacts both mothers and infants. It is associated with significant morbidity and mortality and reported prevalence is 11.5% (Ko, Rockhill, Tong, Morrow, & Farr. (2017). MMWR Morbidity and Mortality Weekly Report, 66(6), 153–158). Although PPD's fundamental pathophysiology remains to be fully illuminated, the influence of changes in perinatal hormones such as allopregnanolone (an endogenous progesterone metabolite) are most promising avenues of research. Conventional treatments for PPD are aligned with treatment strategies for depressive disorders. Brexanolone is a small molecule, neuroactive steroid GABAA receptor allosteric modulator consisting of synthetic allopregnanolone and a solubilizing agent. In early 2019, brexanolone received approval in the United States for the treatment of PPD. Brexanolone is only available through a restricted program and is costly. Animal models demonstrate that progesterone prevents depression‐like behaviors. However, studies of progesterone's effects in women suffering from PPD are few and inconclusive. We hypothesize that orally dosed progesterone will increase concentrations of allopregnanolone in the central nervous system, which should relieve symptoms of PPD.

Hormone Targets for the Treatment of Sleep Disorders in Postmenopausal Women with Schizophrenia: A Narrative Review

“…In postmenopausal women with schizophrenia, the effects of progesterone or other similar compounds have not been tested. Although brexanolone—a synthetic allopregnanolone—has been demonstrated to prevent depression-like behaviors in animal models, the psychotropic properties of progesterone have not been evaluated in postmenopausal schizophrenia [ 42 ].…”

Quantitation of six steroid hormones by ultra‐performance liquid chromatography–tandem mass spectrometry in plasma and prefrontal cortex samples from rats with chronic unpredictable mild stress‐induced depression

“…Excessive glucocorticoids could lead to the impairment of episodic memory performance and resilience (Nehls, 2016). Moreover, the level of sex hormones is different in depression, and always thought to have a neuroprotective effect, including memory enhancing and neuronal excitability, as well as potentially improving the depression symptoms (Barak & Glue, 2020). The diagnostic method of depression is subjective and complicated, and mainly depends on the examination of a psychiatrist.…”

“…For example, 11β‐hydroxysteroid dehydrogenase 2 (11β‐HSD2) is an indicator of glucocorticoid metabolism and its level is highly related to the negative feedback of the HPA axis (Remer et al, 2008). Sex hormones [especially progesterone (PROG)] have been reported to be related to the pathophysiology of postpartum depression, and endogenous PROG is a promising target in postpartum depression research (Barak & Glue, 2020). In animal models, PROG can alleviate depression‐like behavior, which may be due to its neuroprotective effect on depression‐like behaviors and cognitive function (Barak & Glue, 2020).…”

“…Sex hormones [especially progesterone (PROG)] have been reported to be related to the pathophysiology of postpartum depression, and endogenous PROG is a promising target in postpartum depression research (Barak & Glue, 2020). In animal models, PROG can alleviate depression‐like behavior, which may be due to its neuroprotective effect on depression‐like behaviors and cognitive function (Barak & Glue, 2020). Bloch et al (2000) induced hypogonadism to simulate postpartum hormone status in experimental individuals (8 women with postpartum depression and 8 women without a history of postpartum depression).…”

Antidepressant‑like effects of Z‑ligustilide on chronic unpredictable mild stress‑induced depression in rats

“…Progesterone and allopregnanolone are neurosteroids, mediating both the transport of cholesterol from the outer to the inner mitochondrial membrane and the activation of a series of enzymatic reactions to regulate the biosynthesis of neurosteroids (25,26). Studies indicate that reduced levels of progesterone and allopregnanolone are associated with the development of various mental disorders, including anxiety and depression (27,28). Conversely, exogenous administration of progesterone and allopregnanolone may significantly improve depression (29)(30)(31)(32).…”