Effect of Hormonal Therapy on Plasma Testosterone Levels in Prostatic Carcinoma

Abstract

SummaryPlasma concentrations of testosterone were estimated in normal men, in patients before treatment for prostatic cancer, and in patients who had had various forms of endocrine treatment for prostatic carcinoma. There was no decline in plasma testosterone levels with age. Patients with non-metastatic disease had levels similar to those of normal controls, but in advanced metastaticdisease the levels were low. After orchidectomy the plasma testosterone level fell to that found in normal women. In every patient stilboestrol in doses as small as 1 mg three times a day suppressed plasma testosterone at first to negligible amounts, irrespective of the clinical response. Subsequently a small but significant rise in the concentration was always observed over a period of six months' oestrogen therapy. Pituitary ablation with yttrium-90 lowered the plasma testosterone concentration again to negligible amounts in patients who had been on stilboestrol. In advanced metastatic disease this was often associated with relief of pain. Preliminary studies with aminoglutethimide indicate that it can produce biochemical and clinical effects similar to those of pituitary ablation. IntroductionOur purpose was to study the effect on plasma testosterone levels of the various forms of endocrine therapy for prostatic carcinoma. We therefore measured concentrations of plasma testosterone before and during treatment and compared them with those in normal men. The treatments included stilboestrol, orchidectomy, pituitary ablation, and "medical adrenalectomy"

Changes in plasma levels of FSH, LH and testosterone during anti-androgenic hormone therapy for patients with prostatic cancer.

“…The prostatic tumor enlarged somewhat, and there were no visible improve ments in such subjective symptoms as dysuria. Robinson and Thomas (1971). The differences between our findings.…”

“…As a result, they found that each treatment caused a marked fall in the level of plasma testosterone, irrespective of the clinical response. Robinson and Thomas (1971) noted that in prostatic cancer patients, the administration of stilbestrol at a daily dose of only 3 mg could reduce the plasma testosterone level to as low as 10 ng/100 ml or less, a result which was almost equivalent to the effects of larger dosage, 100 mg per day. Commenting on this conspicuous fall in the level of plasma testosterone, which even dipped below female levels, they reasoned that stilbestrol may directly inhibit the production of androgens in the adrenal cortex, exemplified by the fact that the level of testosterone fell more markedly in orchidectomized patients who underwent additional hormonal therapy with stilbestrol than in those who did not.…”

“…In such a case, it is presumed that the administration of an anti-androgenic hormone has failed to suppress the synthesis of androgen in the adrenal cortex, and the adrenal sensitivity to gonadotropin has increased, all contributing to the elevation of the level of plasma testosterone. Robinson and Thomas (1971) within 5 days all the cases showed a reduced plasma testosterone level of bel ow 10 ng/100 ml, with relief of pain. In another experiment where 11 patients received aminoglutethimide in addition to stilbestrol , 7 showed markedly reduced plasma testosterone levels of less than 10 ng/100 ml, and in 4 all traces of pain disappeared.…”

Synthetic androgens suppress the transformed phenotype in the human prostate carcinoma cell line LNCaP

“…Reduction of circulating testosterone from the normal range of 3-6ngml-' of serum (= I x 10-8 M-2 X 10-8M) to about 0.3 ng ml' (= 1 x 10-9 M) by surgical or to about 0.06 ng ml-' (= 2 x 10-0 M) by medical castration (Robinson & Thomas, 1971) leads to at least partial remission of androgen-dependent cancers. Growth properties of LNCaP cells characterised in this report and by others refute the hypothesis of androgen dependence of this cell line.…”

Hipogonadismo prolongado tras la suspensión de tratamiento hormonal en pacientes con cáncer de próstata

“…La supresión persistente de T tras la administración de estrógenos ha sido observada por otros estudios [22][23][24] . En el caso de supresión androgénica mediante análogos LH-RH la posibilidad de hipogonadismo muy prolongado ya fue seña-lado por Stevens 25 que observa que durante 12 meses los pacientes presentaban síntomas de hipogonadismo y ya entonces advertía de que la acción exclusivamente aguda de los análogos LH-RH no se cumplía siempre.…”