phytoestrogens and Hypogonadism

Ageing in man is associated with a decline in testosterone following changes in the hypothalamo-pituitary-testicular axis. This may offset the physiologic equilibrium between oestrogen and androgen and at some point when the ratio of free testosterone to oestradiol reaches a critical level, the oestrogenic gonadotropin suppressive effect predominates with decreased release of FSH and LH. Adding to this endocrinal complexity is the continued peripheral conversion to oestradiol through aromatisation. Although the androgen deficiency is not the sole cause for impotence in the elderly, there is a gradual decrease in nocturnal penile tumescence (NPT) and spontaneous morning erections with ageing. Despite the age related increase in oestrogen levels, the information on the pathophysiological role of the "female hormone" in erectile dysfunction has been scanty. Together with our identification of oestrogen receptors within the penile cavernosum, we have delineated dysfunctional changes on male erection mediated by oestradiol. These findings parallel the recent concerns over environmental oestrogens on fertility declines in young men. Oestrogenic activity is also present in plants and thereby in human diet. These phytoestrogens are structurally and functionally similar to oestradiol and more potent than the environmental oestrogenic chemicals such as organochlorine and phenolic compounds. Thus in the light of growing concerns of possible compromising effects on sexuality by endogenous and environmental oestrogens, we are faced with the scientific need to delineate their role on the mechanism of male erectile pathway in health and disease for clinical correlates and prognostics.

Topics: Aged; Aging; Androgens; Erectile Dysfunction; Estrogens; Humans; Hypogonadism; Isoflavones; Male; Phytoestrogens; Plant Preparations; Testosterone

Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism.. The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycemia and cardiovascular risk markers.. This was a randomized double-blind parallel study.. This study occurred in a secondary care setting in United Kingdom.. Two hundred men with T2DM and a total testosterone level ≤12 nmol/L were included.. Fifteen grams of soy protein with 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily as snack bars for 3 months were administered.. There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in thyrotropin (TSH) and reduction in free thyroxine (fT4; P < 0.01) after SPI supplementation. Glycemic control improved with a significant reduction in hemoglobin A1c (-4.19 [7.29] mmol/mol, P < 0.01) and homeostasis model of assessment - insulin resistance after SPI. Cardiovascular risk improved with a reduction in triglycerides, C-reactive protein, and diastolic blood pressure (DBP; P < 0.05) with SPI vs SP supplementation. There was a 6% improvement in 10-year coronary heart disease risk after 3 months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (P < 0.01), with an increased reactive hyperemia index that was greater for the SPI group (P < 0.05).. Testosterone levels were unchanged and there was a substantial improvement in glycaemia and cardiovascular risk markers with SPI compared with SP alone over 3 months. There was also a substantial increase in TSH and a reduction in fT4.

Topics: Aged; Anthropometry; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Proteins; Double-Blind Method; Humans; Hyperglycemia; Hypogonadism; Isoflavones; Male; Middle Aged; Phytoestrogens; Soybean Proteins; Testosterone

Here we evaluate the effects of oral phytoestrogen supplementation on hypothalamic-pituitary-testicular (HPT) axis in CaP patients.. We recruited 40 men about to undergo radical prostatectomy for CaP to receive either 240 mg of clover phytoestrogens or placebo daily for 2 weeks. Serum hormone levels were measured before and after treatment. In addition, recombinant cell bioassay was used to measure serum androgen bioactivity (ABA).. Phytoestrogen treatment increased serum LH from mean of 3.4-5.2 IU, P = 0.03. Concomitantly, non-significant trend towards decline in serum T, cfT and ABA values was noted. However, mean serum LH/T ratio was upregulated from 0.20 to 0.48 IU/nM, P = 0.004, suggesting compensated hypogonadism. During the course of treatment, serum concentration of equol correlated strongly with the concomitant decrease in ABA (r = -0.586, P = 0.022).. Phytoestrogen treatment interferes with HPT axis in CaP patients by inducing testicular resistance to LH and compensated hypogonadism.

Topics: Administration, Oral; Aged; Androgens; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hypogonadism; Hypothalamus; Luteinizing Hormone; Male; Middle Aged; Phytoestrogens; Pituitary Gland; Prospective Studies; Prostatic Neoplasms; Testis; Testosterone

Isoflavones are phytoestrogens with recognized estrogenic activity but may also affect testosterone, corticosterone and thyroid hormone levels in experimental models. However, the molecular mechanisms involved in these alterations are still unclear. Isoflavones are present in soy-based infant formula, in breast milk after the consumption of soy by the mother and are widely used for the preparation of beverages consumed by toddlers and teenagers. In this sense, we proposed to investigate the effects of soy isoflavone exposure during the prepubertal period, a recognized window of sensitivity for endocrine disruption, over the hypothalamic-pituitary-testicular (HPT) axis. For this, 42 3-week-old male Wistar rats were exposed to 0.5, 5 or 50 mg of soy isoflavones/kg from postnatal day (PND) 23 to PND60. We evaluated body growth, age at puberty, serum concentrations of LH, FSH, testosterone and estradiol, and the expression of the transcripts (mRNA) of genes encoding key genes controlling the hypothalamic-pituitary-testicular (HPT) axis. In the hypothalamus, we observed an increase in Esr1 mRNA expression (0.5 and 5 mg). In the pituitary, we observed an increase in Gnrhr mRNA expression (50 mg), a reduction in Lhb mRNA expression (0.5 mg), and a reduction in Ar mRNA expression. In the testis, we observed an increase in Lhcgr mRNA expression (50 mg) and a reduction in Star mRNA expression (0.5 and 5 mg). The serum levels of LH (5 and 50 mg) and FSH (0.5 mg) were increased, while testosterone and estradiol were reduced. Puberty was delayed in all groups. Taken together, these results suggest that prepubertal consumption of relevant levels of soy isoflavones disrupts the HPT axis, causing hypergonadotropic hypogonadism and altered expression levels of key genes regulating the axis.

Topics: Animals; Corticosterone; Estradiol; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Hypogonadism; Hypothalamus; Isoflavones; Male; Phytoestrogens; Puberty; Rats; Rats, Wistar; RNA, Messenger; Testosterone

Gonadal hormones can modulate brain morphology and behavior. Recent studies have shown that hypogonadism could result in cortical function deficits. To this end, hormone therapy has been used to ease associated symptoms but the risk may outweigh the benefits. Here we explored whether genistein, a phytoestrogen, is effective in restoring the cognitive and central neuronal changes in late middle age and surgically estropause female rats. Both animal groups showed poorer spatial learning than young adults. The dendritic arbors and spines of the somatosensory cortical and CA1 hippocampal pyramidal neurons were revealed with intracellular dye injection and analyzed. The results showed that dendritic spines on these neurons were significantly decreased. Remarkably, genistein treatment rescued spatial learning deficits and restored the spine density on all neurons in the surgically estropause young females. In late middle age females, genistein was as effective as estradiol in restoring spines; however, the recovery was less thorough than on young OHE rats. Neither genistein nor estradiol rectified the shortened dendritic arbors of the aging cortical pyramidal neurons suggesting that dendritic arbors and spines are differently modulated. Thus, genistein could work at central level to restore excitatory connectivity and appears to be potent alternative to estradiol for easing aging and menopausal syndromes.

Topics: Aging; Analysis of Variance; Animals; Dendritic Spines; Estrogens; Female; Genistein; Hormone Replacement Therapy; Hypogonadism; Maze Learning; Neurons; Phytoestrogens; Rats; Rats, Sprague-Dawley; Spatial Learning; Taiwan