Titolo relazione: What’s the safest estrogen balance?: Exploring and managing a critical factor in aging man.
Abstract: The role of estrogens in male physiology has become more evident, as a consequence of the discovery of human models of estrogen deficiency such as estrogen receptor resistance or aromatase deficiency. The discovery of these ‘’experiments of nature’’expanded our knowledge about the physiologic function of estrogens on male health.
Estrogen are involved in different aspects of men physiology: bone maturation and metabolism, cardiovascular protection, spermatogenesis, gonadotropin feedback; they exert effects also on the brain: cognitive function, sexual behavior, affective state, pain and coordination of movement are influenced by estrogens’ activity. In males, testosterone is the major source of plasma estradiol, the main biologically active estrogen, only 20% of which is secreted by the testes while the 80% is produced by aromatization of testosterone inside peripheral tissues and in particular by adipose tissue. Plasma estrone, 5% of which is converted to plasma estradiol, originates from tissue aromatization of mainly adrenal androstenedione. The plasma concentration of estradiol in males is 2-3 ng/dl and its production rate in blood is 25-40 micrograms/24 h; both of these values are significantly higher than in postmenopausal women. Plasma levels of estradiol do not necessarily reflect tissue-level activity as peripherally formed estradiol is partially metabolized in situ; thus, not all enters the general circulation, with a fraction remaining only locally active. Of the factors influencing plasma estradiol levels, plasma testosterone is a major determinant. With aging we have a progressive decresead production of testosterone that can be associated with three different patterns of estradiol production as result of reduced, normal or increased production of estrogens as expression of different level of peripheral aromatases activity and in particular of the age-associated modification of fat mass that is the main producer of estrogens from androgens.
In thin men, with very low BMI(< 18,5),we have a severe decrease of muscle mass and strength (sarcopenia) that’is related to the impressive reduction of anabolic hormones(igf1-dheas,testosterone) and is associated with an important lowering of fat mass with consequent decresead production of estrogens.In this situation, the clinical picture of PADAM is associated to the Estrogen Deficiency Syndrome with severe osteopenia (mainly related to estrogen dediciency) with increased risk of falls and fracture.The concomitant deficiency of androgens and of estrogens promotes also an increased risk for cardiovascular disease(atherosclerosis, myocardial sarcopenia and cachexia).
In the second clinical picture, we have a progressive diminished production of androgens with more or less normal or slight increased production of estrogens due to the physiological increase during aging of abdominal subcutaneous fat and of visceral fat (Abdominal or Central Obesity with WC >_102 cm).
This situation promotes a relative increase of the ratio estradiol/free testosterone.These aging men can be normal or overweight with rispectively normal BMI (18,5-24,9) or increased BMI (25-29,9) depending by the degree of the increase of fat mass versus the level of the reduction of muscle mass.
These men have an increased risk of Inflammaging, Metabolic Syndrome and of its related diseases.
In the third group, aging obese men, we have an impressive increase of fat mass associated with a decrease of muscle mass and strenght with increased BMI(>_ 30)(Global and Central Obesity).
In these men, we find an absolute increase of the ratio estradiol/free testosterone with a clinical syndrome that is the result of androgen deficiency (PADAM) and of estrogen excess (Estrogen Dominance Syndrome).The second and third group of aging men, charaterized by a more or less important increase of fat mass concomitant with the decrease of muscle mass and strength, are also named Sarcopenic Obese.
Disnutrition, increased stress, decreased physical activity, unopposed endogenous oestrogens, xenoestrogens,isulin and leptin excess, are associated with increased aromatase activity with increased endogenous oestrogen and lowered testosterone. The synergistic action of unopposed oestrogen and leptin, compounded by increasing insulin,cortisol and xeno-oestrogen exposure, directly initiate,promote and exacerbate obesity, type 2 diabetes,inflammaging, cardiovascular diseases,dementia, prostatic enlargement and prostate cancer.
(CHAOS SYNDROME or COMPLEX which means Coronary disease, Hypertension, Adult-onset diabetes mellitus, Obesity and/or Stroke syndrome).
In this lecture, are also showed published studies about estrogen deficiency and excess in aging men and their related diseases.