A dose-ranging study of the use of cyclical dydrogesterone with continuous 17 beta oestradiol.
OBJECTIVE
To establish the lowest dose of cyclical dydrogesterone that protects against endometrial hyperplasia induced by continuous 2 mg 17 beta oestradiol, and to study the dose effect on vaginal bleeding and side effects.


METHODS
Double-blind, prospectively randomised dose-ranging study.


METHODS
Menopause clinics in the UK and The Netherlands.


METHODS
Three hundred and seventy-one postmenopausal women with intact uteri, aged 40 to 60.


METHODS
Administration of six 28-day treatment cycles of continuous daily micronised 17 beta oestradiol with a randomly allocated dose of 5 to 20 mg of dydrogesterone added for the last 14 days of each.


METHODS
Histological assessment of adequate progestational endometrial response, bleeding patterns and adverse effects.


RESULTS
The study was completed by 320 subjects (86%). Endometrial transformation occurred in over 94% of those taking 5 mg of dydrogesterone, and in over 97% of those on higher doses, without significant differences between the 10, 15 and 20 mg groups. Acceptable bleeding patterns were found at all doses, with the incidence of withdrawal bleeding rising with increasing dose. The day of onset of bleeding was predictable from cycle to cycle, and occurred later in the 20 mg group than in the others. The incidence of noncyclic bleeding was about 6% at all doses. Withdrawal occurred in 3.3% due to unacceptable bleeding and in 5.4% due to side effects. There was no relation with dose.


CONCLUSIONS
A dydrogesterone-17 beta oestradiol combination hormone replacement therapy confers endometrial protection with an acceptable bleeding pattern and few side effects At least 10 mg of dydrogesterone for 14 days is required for acceptable endometrial protection.
Burch
D J
DJ
Department of Obstetrics and Gynaecology, Rosie Maternity Hospital, Cambridge.
Spowart
K J
KJ
Jesinger
D K
DK
Randall
S
S
Smith
S K
SK
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004394:Dydrogesterone / Q000008:administration & dosage* / Q000009:adverse effects; D004714:Endometrial Hyperplasia / Q000473:pathology / Q000517:prevention & control*; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D014592:Uterine Hemorrhage / Q000139:chemically induced
D004958:Estradiol; D004394:Dydrogesterone