Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy
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).
Timeline
- Start
- 2022-03-15
- Primary completion
- 2026-09
- Completion
- 2027-12
Publications
- Bofill Rodriguez M, Yong LN, Mirkov S, Bekos C, Lethaby A, Farquhar C. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2025 Nov 27;11(11):CD004143. doi: 10.1002/14651858.CD004143.pub6.
- Lundell C, Stergiopoulos N, Blomberg L, Ujvari D, Schuppe-Koistinen I, Kopp-Kallner H, Iliadis SI, Skalkidou A, Hirschberg AL. Breast and endometrial safety of micronised progesterone versus norethisterone acetate in menopausal hormone therapy (PROBES): study protocol of a double-blind randomised controlled trial. BMJ Open. 2024 Oct 23;14(10):e082749. doi: 10.1136/bmjopen-2023-082749.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Norethindrone | Unknown | 0.5 mg | Oral |
| Comparator | Progesterone | Other / unclassified | 100 mg | Oral |
| Comparator | Estradiol | Other / unclassified | 1 mg | Oral |
Indications
No indication recorded.