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Finasteride and Dutasteride do not occupy or inhibit androgen receptors, but rather they inhibit the 5-alpha reductase enzyme primarily responsible for converting testosterone to DHT.1 Although the effects of dutasteride, finasteride and testosterone on DHT metabolism and the hypothalamic receptors are unclear, the findings of a recent study suggest that the 5-alpha reductase system may have a role in the pathophysiology of gender dysphoria and its association with cardiovascular risk factors.2 The endocannabinoid system, in addition to its role in regulating mood and appetite, plays a crucial role in sex differentiation of the brain. Both endocannabinoid receptors and their receptors for the primary metabolite (4-hydroxybenzhydryltetrahydrocannabinol, 4-HBT) and other metabolites (2-arachidonoylglycerol and 3-hydroxy-2-indoleacetic acid) play a role in the development of sexual differentiation of the developing male brain.3 The endocannabinoid system was initially described in the 1970s by Dario Castellanos.4 He defined its involvement in regulation of sexual differentiation by describing its presence in the adult brain, including the anterior hypothalamus. During development, this system is crucial for the development of the testes. It may operate in a coordinated manner to influence the development of secondary sex characteristics, including male sexual orientation.4 Endocannabinoid receptors are expressed in brain regions that regulate sexual behavior in several mammals such as the anterior hypothalamus and in the spinal cord. The endocannabinoid system acts through the G protein cannabinoid receptor type 1 (CB1 R) and its endogenous ligand (endocannabinoids), which are synthesized exogenously and released from the endocannabinoid system in the absence of the CB1 R.5 Endocannabinoids inhibit the synthesis of acetylcholine released from the peripheral nerve endings in the midbrain and mediate autonomic nervous impulses to the adrenal gland.1,6 Endocannabinoids may also have the capacity to modulate the behavior of the hypothalamic complex. Thus, activation of cannabinoid CB2 receptor increases corticosterone and corticosterone increases prolactin and cortisol secretion. It is not known whether a direct role of endocannabinoids in the regulation of sex differentiation is involved in the observed relationship between the effects of finasteride and Dutasteride and their association with cardiovascular risk factors such as hypertension. Previous studies have reported that finasteride and Dutasteride decreased circulating plasma levels of testosterone, DHT, and gonadotropin-releasing hormone ( Similar articles:
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