Objective and design: No data are available on effects of long-term exposure to oestrogen on bioactivity of gonadotrophins in men. We studied the effects of a 6-month oestrogen therapy on serum FSH and LH bioactivity (B), immunoreactivity (I) and isohormone distribution, and on serum I-inhibin levels, in patients with prostatic carcinoma.
Patients: Eleven men with advanced prostatic cancer were studied, each receiving 160 mg of polyoestradiol phosphate (Estradurin) once a month intramuscularly for 6 months.
Measurements: Serum samples were collected before, and after 2 and 6 months of oestrogen treatment. Serum B- and I-FSH levels were measured by immature rat granulosa cell bioassay and immunofluorometric (IFMA, Delfia) assay, respectively, and those of B- and I-LH by mouse interstitial cell bioassay and IFMA, respectively. Serum oestradiol (E2) concentrations were measured by IFMA assay, and serum testosterone (T) and inhibin levels by radioimmunoassay. Isoelectric focusing was used for fractionation of the FSH and LH isoforms.
Results: The pretreatment levels of B-FSH and I-FSH were 84.7 +/- 21.6 and 11.4 +/- 3.2 IU/l (mean +/- SEM), respectively, and the B/I ratio of FSH was 8.3 +/- 1.0. The pretreatment levels of B-LH and I-LH were 23.5 +/- 3.2 and 10.1 +/- 2.3 IU/l, respectively, and the B/I ratio was 3.0 +/- 0.4. After 6 months of oestrogen therapy, B-FSH and I-FSH decreased to 37.5 +/- 8.1 (P < 0.05) and 1.3 +/- 0.3 IU/l (P < 0.01), respectively, but the B/I ratio of FSH increased to 28.5 +/- 4.2 (P < 0.05). B- and I-LH levels decreased in 6 months to 7.4 +/- 0.9 and 2.3 +/- 0.5 IU/l (P < 0.01), respectively, but no change was found in the B/I ratio of LH. Serum T levels decreased from 19.0 +/- 2.6 to 2.7 +/- 0.9 nmol/l (P < 0.01) during the 6-month treatment, and the respective E2 levels increased from 0.2 +/- 0.01 to 4.4 +/- 0.5 nmol/l (P < 0.01). Serum I-inhibin levels were analysed from eight patients. The levels at 0, 2 and 6 months were 0.81 +/- 0.09, 0.50 +/- 0.03 and 0.54 +/- 0.01 microgram/l, respectively. Gonadotrophins in the pretreatment and 6-month samples of four patients were analysed by isoelectric focusing. In FSH of all subjects, and in LH of three subjects, a shift from acidic to more basic isoforms occurred after oestrogen therapy. This is in keeping with the increase of the B/I ratio of FSH. With LH, the isoform shift occurred between fractions with similar B/I ratios, and hence there was no shift in the overall B/I ratio.
Conclusions: Oestrogen therapy of men suppressed bioactive and immunoreactive levels of gonadotrophins. The B/I ratio of FSH increased, and this increase was associated with a shift in the isohormone profile to more basic forms. In contrast, no change occurred in the B/I ratio of LH, even though changes in the isohormone profile were observed. Hence, not all changes in the isohormone distribution of gonadotrophins result in changes of the intrinsic in-vitro bioactivity.