Гормонотерапия при депрессиях

Extensive preclinical studies demonstrate that estrogen can, in many ways, modulate molecular pathways involved in monoaminergic neurotransmission (serotonin [5-hydroxy-tryptamine receptors or 5-HT], norepinephrine [NE]); these systems are critical for mood and behavior regulation. Estradiol (E2) administration decreases the activity of monoamine oxidases (MAO-A and MAO-B), which are enzymes involved in 5-HT degradation; E2 also increases both isoforms of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis. Thus, E2 administration results in an overall increase in 5-HT synthesis and availability. E2 also regulates the 5-HT transporter, which plays an integral role in 5-HT reuptake from the synaptic cleft to the pre-synaptic neuron. Furthermore, by downregulating 5-HT1a autoreceptors and upregulating 5-HT2a receptors, E2 increases the amount of serotonin found in the synapse and increases the amount available for postsynaptic transmission. E2 is capable of inducing antidepressant effects in ovariectomized rats when administered in combination with subdoses of fluoxetine, which suggests that E2 can also augment antidepressant agents. In sum, estrogen appears to work via different pathways that ultimately result in increased serotonin production and transmission. Similarly, estrogens increase NE availability by decreasing expression of MAOs and increasing the activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthetic pathway of catecholamine.

Clinically, E2 administration to depressed perimenopausal and early postmenopausal women demonstrated antidepressant effects of similar magnitude to that observed with antidepressant agents. Randomized, double-blind, placebo-controlled studies reported significantly greater reduction in depressive symptoms with the use of transdermal estradiol (17β-estradiol, 50-100 µg), compared to placebo.[3] In some studies, the antidepressant effects of estrogen were observed even in the absence of concomitant vasomotor symptoms.[4] Notably, studies on E2 therapy for older, postmenopausal women suffering from depression resulted in small, nonsignificant reduction in depressive symptoms. Taken together, these observations suggest that: 1) estrogen’s antidepressant effect may have a “critical window” or optimal timing, possibly during the menopause transition and early postmenopausal years; and 2) the potential benefits of E2 therapy for the improvement of mood symptoms may occur independent from changes or improvement of vasomotor symptoms. In sum, preclinical and clinical evidence suggest that estrogen-based therapies can contribute to greater therapeutic responses and potentially boost the response to traditional antidepressant agents, along with well-established benefits for vasomotor, sexual, and other menopause-related symptoms.

HT in Managing Depression in a Patient Using SSRIs