Continuous infusions of Delta(4)-androstenedione-7-(3)H and testosterone-7-(3)H have been used to demonstrate that these androgens are converted to estrone and 17beta-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [chi(-PRO)] and free precursor steroid [chi(-PRE)], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [rho](BB) (AE1), for androstenedione conversion to estrone ([rho](BB) (AE1) = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [rho](BB) (TE2), for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [rho](BB) value are greater in males than females. For the androgen interconversions, [rho](BB) (AT) is 4.5% in males and 2.2% in females; [rho](BB) (TA) is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03.

/pdf/conversion-of-blood-androgens-to-estrogens-in-normal-adult-tq80uk936b.pdf

Conversion of blood androgens to estrogens in normal adult men and women

The role of the human testis in the production of 17beta-estradiol (E(2)) was investigated by determining the concentration of E(2) and testosterone in peripheral and spermatic vein plasma samples. Specimens were obtained from eight normal men, three men with hypogonadism, and two patients with the incomplete form of the feminizing testes syndrome. For comparison, similar studies were performed in four monkeys, 10 mongrel dogs, and 4 additional dogs who were given 1000 IU of human chorionic gonadotropin/day for 5 days. Plasma E(2) was measured by radioimmunoassay utilizing sheep anti-E(2) serum preceded by ether extraction and thin layer chromatographic separation of plasma steroids. Procedural blanks, which were subtracted from all reported values were 14.1+/-0.74 (SEM) pg for deionized water and 13.1+/-0.66 pg for charcoaladsorbed pooled male plasma. Pooled male and pooled female control plasmas averaged 17+/-0.71 pg/ml and 95+/-6.9 pg/ml, respectively; individual adult male specimens ranged between 8 and 28 with a mean of 18+/-1.4 pg/ml. In the eight normal men, the mean peripheral vein E(2) concentration was 20+/-1.6 pg/ml, while the spermatic vein concentration was 50 times as great, 1049+/-57 pg/ml. All three patients with testicular abnormalities had low spermatic vein E(2) concentrations (160, 280, and 416 pg/ml). Lesser E(2) gradients were found across the simian (3-fold) and canine (approximately 12-fold) testes. Testicular testosterone gradients (human 110-, simian 10-, and canine 77-fold) were greater than the E(2) gradients in all three species. In four dogs, HCG treatment elicited a 6-fold increase in peripheral and a 9-fold increase in spermatic vein testosterone concentrations; however, peripheral and spermatic vein E(2) concentrations did not differ from control values. Spermatic vein E(2) concentrations were > 4600 and 2210 pg/ml (post-HCG) in two patients with the incomplete form of the feminizing testes syndrome. Postorchiectomy, peripheral E(2) and testosterone concentrations fell precipitously in both patients, confirming the major contribution of the testes, in this syndrome, to circulating E(2) and testosterone. These studies provide direct evidence that the human testic secretes estradiol.

/pdf/estradiol-and-testosterone-secretion-by-human-simian-and-2x19409w94.pdf

Estradiol and Testosterone Secretion by Human, Simian, and Canine Testes, in Males with Hypogonadism and in Male Pseudohermaphrodites with the Feminizing Testes Syndrome

ContextAndrostenedione, a precursor to testosterone, is
marketed to increase blood testosterone concentrations as a natural
alternative to anabolic steroid use. However, whether androstenedione
actually increases blood testosterone levels or produces anabolic
androgenic effects is not known.ObjectivesTo determine if short- and long-term oral
androstenedione supplementation in men increases serum testosterone
levels and skeletal muscle fiber size and strength and to examine its
effect on blood lipids and markers of liver function.Design and SettingEight-week randomized controlled trial
conducted between February and June 1998.ParticipantsThirty healthy, normotestosterogenic men (aged 19-29
years) not taking any nutritional supplements or androgenic-anabolic
steroids or engaged in resistance training.InterventionsTwenty subjects performed 8 weeks of
whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the
men were randomized to either androstenedione, 300 mg/d
(n=10), or placebo (n=10). The effect
of a single 100-mg androstenedione dose on serum testosterone and
estrogen concentrations was determined in 10 men.Main Outcome MeasuresChanges in serum testosterone and estrogen
concentrations, muscle strength, muscle fiber cross-sectional area,
body composition, blood lipids, and liver transaminase activities based
on assessments before and after short- and long-term androstenedione
administration.ResultsSerum free and total testosterone concentrations were not
affected by short- or long-term androstenedione administration. Serum
estradiol concentration (mean [SEM]) was higher (P<.05) in
the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30]
pmol/L), and 8 (280 [20] pmol/L) weeks compared with
presupplementation values (220 [20] pmol/L). The serum estrone
concentration was significantly higher (P<.05) after 2 (153
[12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione
supplementation compared with baseline (106 [11] pmol/L). Knee
extension strength increased significantly (P<.05) and
similarly in the placebo (770 [55] N vs 1095 [52] N) and
androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of
the mean cross-sectional area of type 2 muscle fibers was also similar
in androstenedione (4703 [471] vs 5307 [604] mm2;
P<.05) and placebo (5271 [485] vs 5728 [451]
mm2; P<.05) groups. The significant
(P<.05) increases in lean body mass and decreases in fat
mass were also not different in the androstenedione and placebo groups.
In the androstenedione group, the serum high-density lipoprotein
cholesterol concentration was reduced after 2 weeks (1.09 [0.08]
mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL];
P<.05) and remained low after 5 and 8 weeks of training and
supplementation.ConclusionsAndrostenedione supplementation does not increase
serum testosterone concentrations or enhance skeletal muscle
adaptations to resistance training in normotestosterogenic young men
and may result in adverse health consequences.

https://jamanetwork.com/journals/jama/articlepdf/190128/JCI80062.pdf

Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men: A Randomized Controlled Trial

Five men with advanced breast cancer were treated with aminoglutethimide (AG) plus replacement dose hydrocortisone. None of the 4 patients with intact testes responded, although 3 did so subsequently to tamoxifen. The previously orchidectomized patient responded to aminoglutethimide for 14 months. Oestrone and oestradiol were suppressed by AG in all patients, but not to the levels achieved by orchidectomy. AG produced substantial further oestrogen suppression in the orchidectomized patient and should only be used after orchidectomy.

Role of aminoglutethimide in male breast cancer.

An-drostenedioneisalsoproducedbysomeplants and has recently been mar-ketedasaproductforincreasingbloodtestosteroneconcentrationstobeusedas a natural alternative to anabolic ste-roid use.However,theinterconversionsofan-drostenedioneandtestosteronetootherandrogens, as well as to estrogens, arecomplex.Inadditiontoservingasapre-cursor to testosterone, androstenedi-onemaybeconvertedintoestrogensdi-rectly.

Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men

Tritiated (7α-3H) testosterone was injected intravenously into normal and hypogonadal men after which all urine was collected for 5 days. The urine was assayed for estrone, 17β-estradiol, estriol, ...

B. J. Epstein

Papers

Estrogen synthesis in normal and hypogonadal men: quantitative studies on the precursor role of testosterone