Effects of orally active oestrogen formulations in perimenopausal women

Four different orally active oestrogenic formulations, viz oestradiol valerate (E2V) 2mg, oestrone sulphate (E1S) 2.5mg, oestriol (E3 ) 10 mg and oestriol (E3 ) 5 mg in combination with oestrone sulphate (E1S) 1.25 mg were investigated in 12 peri-menopausal women , using a cross-over design. The oestrogens were given alone for eleven days, then combined with 250 μg levo-norgerstrel daily for a period of ten days, followed by placebo administration for seven days. During the oestrogen treatment, vaginal smears and blood samples for the estimation of peripheral levels of gonadotrophins and a variety of steroids were taken daily. An endometrial biopsy and samples for microfluorometric DNA-analysis were obtained on the last day of the oestrogen treatment. The oral administration of E1S or E2V resulted in high plasma levels of E1S followed, in descending order, by those of E3S, E1 and E2S. Oestriol treatment gave rise to high E3S and lower E3 levels. All formulations significantly suppessed follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but the effect of E3 given alone was weaker than that of the other formulations. Increased proliferative activity of the endometrium was observed in all the groups , although E3 given alone had a less pronounced effect. Occasional intense basal vacuolation was seen. There was a slight but significantly increased maturation of the vaginal epithelium in the women treated with E1S, but not in the other groups. It was concluded that the oestrogenic effect of daily doses of 10 mg E3 is weaker than that of the other formulations, at least in the case of the indices investigated.