Effect of chronic daily oral administration of 17 beta-oestradiol and norethisterone on the isoforms of serum gonadotrophins in post-menopausal women.
OBJECTIVE
Chronic treatment with 17 beta-oestradiol (E2) implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post-menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post-menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum.


METHODS
Serum samples were obtained from 20 post-menopausal women, mean age 60 years (range 50-72 years), treated with continuous daily oral medication of 2 mg E2 combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2 in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0.1% agarose suspension. Sera from 20 post-menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post-menopausal women treated with E2 implants and on women with normal menstrual cycles.


RESULTS
The E2 level in the oral-E2 + NETA treated women was 198-610 pmol/l, within the range expected during the mid-luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2 implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0.001), the E2 implant group (P < 0.001) and at the follicular phase of the cycle (P < 0.01). The mean FSH level was similar to that of the follicular phase and the E2 implant group but lower than that of the controls (P < 0.001) and higher than at the luteal phase of the cycle (P < 0.01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0.001) but more acidic than those for the E2 implant group (P < 0.01; P < 0.001) and for different phases of the menstrual cycle (P < 0.05; P < 0.001). The mean degree of charge heterogeneity of FSH was larger (P < 0.01), while that of LH was smaller (P < 0.01), than for the controls. The mean concentrations of SHBG in the oral E2 + NETA group, the E2 implant group and the controls were similar.


CONCLUSIONS
Chronic oral therapy with 2 mg 17 beta-oestradiol combined with 1 mg norethisterone in post-menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2 implant and the oral E2 + NETA treated groups may be due to the differences in route of administration of E2 or to the effect of norethisterone or both.
Wide
L
L
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Naessén
T
T
Phillips
D J
DJ
D000368:Aged; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors*; D008597:Menstrual Cycle / Q000097:blood; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage*; D017698:Postmenopause / Q000097:blood*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009640:Norethindrone