Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy

• Status: Recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: Female

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Angelica Lindén Hirschberg
• Treatments: Estrogens; Norethindrone; Norethindrone Acetate; Progesterone

Criteria

Inclusion Criteria:

• Age 45-60 years

• BMI > 19 kg/m2 and ≤ 32 kg/m2

• Intact uterus

• In case of previous MHT use, washout 8 weeks for oral MHT and 4 weeks for transdermal MHT or local estrogen treatment before screening

• Written informed consent

Exclusion Criteria:

• Previous history or risk factors for breast cancer, breast cancer in situ or abnormal mammogram at baseline as assessed clinically by a radiology expert

• Previous history or risk factors for endometrial cancer or hyperplasia or abnormal/proliferative endometrial biopsy at baseline

• Vaginal bleeding

• Any concomitant medical treatment except for well-controlled hypertension, non-insulin treated type 2 diabetes, asthma and hypothyroidism

• History or presence of or risk factor for cardiovascular disease including thromboembolic disorder or cerebrovascular disease

• History or presence of liver and gallbladder disease, familial hyperlipidemia, epilepsy or classical migraine with aura

• History or presence of clinically significant depression or other psychiatric disorder that might in anyway compromise the performance of the trial or undermine its scientific validity

• Porphyria, Systemic lupus erythematosus and otosclerosis

• Current use of MHT or local estrogen treatment

• Alcohol and/or drug abuse

• Clinically significant findings on physical and/or gynecological examination at baseline

• Hypersensitivity to any of the study treatments