Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study

• Published in: BJOG : an international journal of obstetrics and gynaecology Vol. 109; no. 8; pp. 958 - 960
• Main Authors: Panay, N., Zamblera, D., Sands, R., Jones, J., Alaghband‐Zadeh, J., Studd, J.W.W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2002; Blackwell
• Subjects: Absorptiometry, Photon - methods; Aged; Biological and medical sciences; Body Mass Index; Bone Density - drug effects; Bone Remodeling - drug effects; Drug Implants; Drug Therapy, Combination; Endometrium - drug effects; Estradiol - administration & dosage; Female; Genital system. Reproduction; Humans; Lumbar Vertebrae; Medical sciences; Middle Aged; Norethindrone - administration & dosage; Pharmacology. Drug treatments; Progesterone Congeners - administration & dosage; Prospective Studies; Human; Replacement therapy; Implant; Toxicity; Low dose; Treatment efficiency; Diseases of the osteoarticular system; Estrogen; Bone disease; Estradiol; Progestagen; Prevention; Osteoporosis; Chemotherapy; Postmenopause; Adult; Female; Combined treatment; Norethisterone; Elderly
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/j.1471-0528.2002.00308.x

The anxiety regarding no‐bleed regimens is that breakthrough bleeding and endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol implants can be adequately opposed by a low dose of progestogen protecting against osteoporosis. Twenty‐two patients were recruited to the study. The mean age was 62 years and body mass index of 26.5. Median oestradiol rose from 77 pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness remained unchanged at 4 mm and only two women withdrew with bleeding problems. There was one case of proliferative endometrium at one year—all others samples were either atrophic or secretory. Lumbar bone density (L2–L4) rose significantly from 0.939 to 0.992 g/cm2 (+5.6%, P= 0.005) and the total femoral density rose from 0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly (serum type 1 procollagen C terminal peptide, P1CP = 112–114, P= 0.0376) and bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0–2.9, P= 0.2863). E25 implants and low dose progestogen appear to avoid endometrial hyperplasia and bleeding problems while increasing bone density.