Nelson Vergel
Founder, ExcelMale.com
Estrogen Response to Testosterone Therapy (TTh)
The response of estrogen to T administration was studied by Lakshman et al. In a group of young men and another group of older men, T enanthate was administered after pharmacologic gonadotropin suppression with leuprolide. Both total and free E2 levels increased with T administration in a dose-dependent fashion that was consistent with saturable Michaelis-Menten kinetics. There was a higher rate of aromatization in the group of older men that was partially but not completely explained by greater fat mass [111].
These results suggest that in T-deficient men, TTh should result in an increase in serum E2, possibly with greater increases in older or obese men. A PubMed review was performed to identify studies of TTh in which changes in E2 were reported. We limited our review to studies in T-deficient older men, without obvious chronic physical or mental illness or debilitation. There is substantial intra-assay variation and E2 levels are not directly comparable between studies. Additionally, interassay variation may be higher for low E2 levels [25].
In five of the six studies, mean baseline E2 was near the lower limit of normal. Only Chiang et al. reported levels that are generally considered toward the upper limit of normal although an assay reference range was not reported [99]. In five studies, E2 increased relative to baseline or placebo, but this only reached significance in three of the four largest studies. The increases in E2 paralleled increases in T, which is in accordance with the results shown by Lakshman et al.
Additionally, there was an overall trend to greater increases with T injections, compared with topical therapies, although this was not rigorously evaluated. This may be due to higher peak serum T concentrations. Intramuscular T undecanoate may lead to greater increase in E2 over T enanthate [101].
In these studies, the number of patients who developed E2 levels above the normal range was not reported, however mean values were all well within normal limits. Interestingly, in some cases, an initial elevation in E2 was followed by decreased E2 after prolonged TTh [98]. This may be due to reduced adipose mass or decreased T concentrations. This observation was also seen in the study by Schubert et al. in which 14 of 32 patients treated for 28 months with intramuscular T undecanoate demonstrated an initial increase in E2 followed by a subsequent decline [101]. The influence of fat mass on E2 was not explored, but average BMI was 29.1 ± 5.1 kg/m2, near the threshold for obesity, and it is known that fat mass reliably decreases with TTh.
Amory et al. studied patients receiving T enanthate with or without finasteride. The authors found that E2 increased after therapy in both groups, with greater E2 increases for patients receiving finasteride. The authors commented on E2 results without providing actual data [112]. Inhibition of the conversion of T to DHT may result in increased availability of T as a substrate for aromatization to E2. DHT is not aromatizable but may be converted to an estrogen, 3bD, though aromatase-independent pathways. Compared with E2, 3bD is a weak binder of the ER and its clinical relevance is unknown [9]. It is possible that five alpha reductase inhibitors may increase estrogenic activity in men, as suggested by the occasional development of gynecomastia in men receiving these medications.
Source:
Estrogens in Men: Clinical Implications for Sexual Function and the Treatment of Testosterone Deficiency
Ravi Kacker, MD,* Abdulmaged M. Traish, PhD,† and Abraham Morgentaler, MD*
*Beth Israel Deaconess Medical Center, Harvard Medical School, Urology, Boston, MA, USA; †Laboratory for Sexual Medicine Research, Boston University, Boston, MA, USA
International Society for Sexual Medicine
The response of estrogen to T administration was studied by Lakshman et al. In a group of young men and another group of older men, T enanthate was administered after pharmacologic gonadotropin suppression with leuprolide. Both total and free E2 levels increased with T administration in a dose-dependent fashion that was consistent with saturable Michaelis-Menten kinetics. There was a higher rate of aromatization in the group of older men that was partially but not completely explained by greater fat mass [111].
These results suggest that in T-deficient men, TTh should result in an increase in serum E2, possibly with greater increases in older or obese men. A PubMed review was performed to identify studies of TTh in which changes in E2 were reported. We limited our review to studies in T-deficient older men, without obvious chronic physical or mental illness or debilitation. There is substantial intra-assay variation and E2 levels are not directly comparable between studies. Additionally, interassay variation may be higher for low E2 levels [25].
In five of the six studies, mean baseline E2 was near the lower limit of normal. Only Chiang et al. reported levels that are generally considered toward the upper limit of normal although an assay reference range was not reported [99]. In five studies, E2 increased relative to baseline or placebo, but this only reached significance in three of the four largest studies. The increases in E2 paralleled increases in T, which is in accordance with the results shown by Lakshman et al.
Additionally, there was an overall trend to greater increases with T injections, compared with topical therapies, although this was not rigorously evaluated. This may be due to higher peak serum T concentrations. Intramuscular T undecanoate may lead to greater increase in E2 over T enanthate [101].
In these studies, the number of patients who developed E2 levels above the normal range was not reported, however mean values were all well within normal limits. Interestingly, in some cases, an initial elevation in E2 was followed by decreased E2 after prolonged TTh [98]. This may be due to reduced adipose mass or decreased T concentrations. This observation was also seen in the study by Schubert et al. in which 14 of 32 patients treated for 28 months with intramuscular T undecanoate demonstrated an initial increase in E2 followed by a subsequent decline [101]. The influence of fat mass on E2 was not explored, but average BMI was 29.1 ± 5.1 kg/m2, near the threshold for obesity, and it is known that fat mass reliably decreases with TTh.
Amory et al. studied patients receiving T enanthate with or without finasteride. The authors found that E2 increased after therapy in both groups, with greater E2 increases for patients receiving finasteride. The authors commented on E2 results without providing actual data [112]. Inhibition of the conversion of T to DHT may result in increased availability of T as a substrate for aromatization to E2. DHT is not aromatizable but may be converted to an estrogen, 3bD, though aromatase-independent pathways. Compared with E2, 3bD is a weak binder of the ER and its clinical relevance is unknown [9]. It is possible that five alpha reductase inhibitors may increase estrogenic activity in men, as suggested by the occasional development of gynecomastia in men receiving these medications.
Source:
Estrogens in Men: Clinical Implications for Sexual Function and the Treatment of Testosterone Deficiency
Ravi Kacker, MD,* Abdulmaged M. Traish, PhD,† and Abraham Morgentaler, MD*
*Beth Israel Deaconess Medical Center, Harvard Medical School, Urology, Boston, MA, USA; †Laboratory for Sexual Medicine Research, Boston University, Boston, MA, USA
International Society for Sexual Medicine
