Effects of IM Testosterone Dose & Age on the Conversion to E2 / DHT

[steroid.com 1]

We've had great debate here on the use of an AI to control aromatization. We've also discussed the effects of Testosterone dosages and how it can effect serum levels of E2 and DHT. Below is a summary of a study (and link to the full study) published in The Journal of Clinical Endocrinology & Metabolism, August 2010.

Like all research there are probably flaws in this work; but I think it noteworthy for our members who like to self educate especially about the subject matter of this research which in one way or another effects us all.

What I find interesting, and what we know, is that age (increased levels of body fat) and dosages of injected Testosterone, along with genetics which plays a big part in metabolism, increase E2 and DHT serums levels and validates the use of an AI to control and manage.

Here ya go:

Endocrine Research
http://j***.endojournals.org/content/95/8/3955.full

The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men

Kishore M. Lakshman,
Beth Kaplan,
Thomas G. Travison,
Shehzad Basaria,
Philip E. Knapp,
Atam B. Singh,
Michael P. LaValley,
Norman A. Mazer1 and
Shalender Bhasin1

- Author Affiliations

Division of Endocrinology, Diabetes, and Nutrition, and Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies (K.M.L., T.G.T., S.Ba., P.E.K., S.Bh.), Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 02118; Lahey Clinic Medical Center (B.K.), Burlington, Massachusetts 01805; Charles Drew University (A.B.S.), Los Angeles, California 90059; Department of Biostatistics (T.G.T., M.P.L.), Boston University School of Public Health, Boston, Massachusetts 02118; and Hoffman LaRoche (N.A.M.), CH-4070 Basel, Switzerland

Address all correspondence and requests for reprints to: Kishore M. Lakshman, M.D., M.P.H., Division of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Medical Center, 670 Albany Street, Second Floor, Boston, Massachusetts 02118. E-mail: [email protected].


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Abstract

Background: During testosterone (T) therapy, T is partly converted to 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT). Effects of age, testosterone dose, and body composition on total and free E2 and DHT levels are unknown.

Objective: We evaluated age and dose-related differences in E2 and DHT levels in response to graded doses of testosterone enanthate in young and older men.

Methods: Fifty-one young (aged 19–35 yr) and 52 older (aged 59–75 yr) men completed treatment with monthly injections of a GnRH agonist plus randomly assigned weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg) for 5 months.

Results: During testosterone administration, total and free E2 levels increased dose-dependently (dose effect, P < 0.001) in both young and older men. Total and free E2 levels and E2:T ratios during T administration were higher in older than young men, but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels, percentage fat mass, and SHBG. DHT levels and DHT:T ratios were dose-related but did not differ between young and older men. Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics. The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5α-reductase, independent of age. The Vmax parameter for E2 was 40% higher in older men than younger men, but Vmax for DHT was not significantly different between age groups.

Conclusions: During im testosterone administration, E2 and DHT levels exhibit saturable increases with dose. The rate of whole body aromatization is higher in older men, partly related to their higher percentage fat mass, SHBG, and testosterone levels.

[bass]

thanks for the post GD. as usual the link was filtered out!

[ecdysone]

Thanks for the reference GD. I read this one some time ago and was confused as to exactly what they were trying to prove.

They first show there is an age-related effect for E2 production, but then pretty much negate that concept by simply correcting for body fat (with the idea that older men have more body fat than younger).

My "take away lesson":

The clinical consequences of higher E₂ levels and higher E₂:T ratios in older men remain poorly understood. In longitudinal studies in older men, higher E₂ levels have been associated with adverse outcomes such as stroke and cognitive decline... and with the increased risk of metabolic syndrome and type 2 diabetes mellitus.

Very low E₂ levels have been associated with bone loss and fracture risk, insulin resistance and premature atherosclerosis, and higher risk of mortality in elderly men.

Hence, too much as well as too little estrogen may be detrimental to the health in men. Further research is needed to elucidate the role of estrogen in men’s health, including defining thresholds beyond which E₂ levels might be detrimental.

And, an interesting statement buried in the research:

"Anecdotally, high doses of testosterone and other androgens have been reported to be associated with gynecomastia. Our data indicate that the occurrence of gynecomastia with high doses of testosterone cannot be explained on the basis of high estradiol to testosterone ratios; however, the high levels of E₂ attained at high doses may be sufficient to account for it "