Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy
Status:
Recruiting
Trial end date:
2027-12-01
Target enrollment:
Participant gender:
Summary
About one third of all women during menopausal transition have significant climacteric
symptoms with considerable impact on quality of life. Meta-analysis has shown a beneficial
risk profile with menopausal hormone therapy (MHT) for women 50 to 60 years. Still, there is
a great need to find safe MHT able to control excessive endometrial stimulation by estrogen
without stimulatory effects on the breast by the combination of estrogen/progestogen. Recent
observational studies indicate a lower risk for breast cancer using micronized progesterone
(mP) combined with estrogen but increased risk of endometrial cancer than by standard MHT. In
a randomized trial, the balance between benefits and risks of mP vs. progestogens
(norethisterone (NETA)) in combination with estrogen will be explored. For apparent reasons,
long-term largescale clinical trials with endometrial and breast cancer as the primary
endpoints, are not feasible. However, much knowledge can be obtained using relevant surrogate
markers. Mammographic breast density is a strong risk factor for breast cancer, and
endometrial hyperplasia is a strong risk factor for endometrial cancer. The primary objective
is to compare the effects of one year treatment with mP versus progestogen, in combination
with estradiol on mammographic breast density. Furthermore, to evaluate the effect of one
year treatment with mP in continuous combination with estradiol on endometrial pathology
(hyperplasia and cancer).