Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial

Area of Science:

• Reproductive Endocrinology
• Postmenopausal Health
• Hormone Replacement Therapy

Background:

• Menopausal hormone therapy (HT) is used to manage symptoms and prevent bone loss.
• Continuous combined HT aims to eliminate withdrawal bleeding and reduce side effects.
• Low-dose regimens are being explored for improved tolerability and long-term safety.

Purpose of the Study:

• To evaluate the efficacy and acceptability of continuous low-dose estrogen and progestogen therapy.
• To compare three different progestogens (medroxyprogesterone acetate, levonorgestrel, norethisterone) in combination with low-dose estrogen.
• To assess the impact of the lowest effective estrogen dose on menopausal symptoms and other outcomes.

Main Methods:

• A 12-month, prospective, open-label, randomized trial involving 75 postmenopausal women.
• Participants transitioned from conventional HT to a continuous daily regimen of 0.3 mg conjugated equine estrogens (CEE) plus one of three low-dose progestogens.
• Outcomes included menopausal symptom scores, bleeding patterns, endometrial biopsies, bone density, and serum lipids.

Main Results:

• Amenorrhea was achieved in 93% of women by 12 months.
• Endometrial biopsies showed atrophic endometrium in most participants.
• All regimens were bone-sparing, did not alter lipid profiles, and had minimal side effects.
• Norethisterone was associated with a higher amenorrhea rate at six months compared to levonorgestrel and medroxyprogesterone acetate.

Conclusions:

• Low-dose continuous estrogen and progestogen therapy is an appropriate option for postmenopausal women seeking to eliminate withdrawal bleeding and reduce symptoms.
• The tested regimens demonstrated bone-sparing effects and were well-tolerated.
• Further long-term studies are needed to confirm benefits for preventing osteoporotic fractures, cardiovascular disease, and endometrial cancer.