Endometrial changes after long-term use of continuous oestrogen and cyclic progestogen

Area of Science:

• Reproductive Endocrinology
• Gynecology
• Hormone Therapy

Background:

• Primary ovarian failure and the climacteric present unique hormonal challenges.
• Estrogen therapy is common for managing menopausal symptoms.
• Unopposed estrogen can lead to endometrial hyperplasia, a precursor to cancer.

Purpose of the Study:

• To evaluate the long-term effects of sequential estrogen-progestogen therapy on the endometrium.
• To determine if a specific regimen prevents endometrial hyperplasia in menopausal women.

Main Methods:

• Sequential treatment with oestradiol-oestriol and norethisterone acetate was administered.
• Endometrial biopsies were taken after the estrogen-only phase of the cycle.
• Histological examination assessed endometrial changes, including hyperplasia and carcinoma in situ.

Main Results:

• After a mean of 5 years of treatment, all endometrial biopsies showed a proliferative endometrium.
• No signs of endometrial hyperplasia or carcinoma in situ were observed.
• A low dose of norethisterone acetate (1 mg) for 10 days prevented hyperplasia.

Conclusions:

• Cyclic estrogen therapy combined with a progestogen, like norethisterone acetate, is safe for long-term use.
• This regimen effectively prevents endometrial hyperplasia during menopausal hormone therapy.
• Hormone replacement therapy can be safely managed with appropriate progestogen co-administration.