British Journal of Obstetrics and Gynaecology zyxwvut November 1997, Vol. 104, Supplement 16, pp. 19-25 Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy *E. Hirvonen zyxwvutsr Senior Lecturer, zyxwvut TC. Lamberg-Allardt Senior Lecturer, $K. S. Lankinen Medical Advisor, $P. Geurts Medical Writer, SG. WilCn-Rosenqvist Head zyx of Department *Department of Obstetrics and Gynecology, Helsinki Universiry Central Hospital, Helsinki, Finland: fMinerva Foundation, Institute j b r Medical Research, Helsinki, Finland: $Research and Development, Orion Corporation Orion Pharma, Espoo, Finland; $Medical Services Department, NV Organon, Oss. The Netherlands Objective To compare two doses of a transdermal oestradiol gel (Divigel@/Sandrena@) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina@/Dilena@). Design Two-year, randomised, open-label, comparative study. Setting Menopausal outpatient clinic in Helsinki. Subjects Postmenopausal women with climacteric complaints or already using HRT. Interventions (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last I0 days. In all groups, each treatment period was followed by a 7-day medication-free interval. Main outcome measures Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety. Results With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourdble changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation. Conclusions Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient. well-tolerated form of HRT. INTRODUCTION During the last decade, several alternative dosage forms to oral oestrogens have emerged, such as vaginal rings, pessaries, patches, implants and creams. These parenteral forms of HRT are mainly aimed at avoiding the first pass metabolism that oral oestrogens undergo in the gut wall and the liver. Unlike oral oestrogens, with transdermal oestrogens a physiological, premenopausal E, zyxwvu : E2 ratio of around 1 is achieved’,*. In addition, transdermal oestrogens do not cause induction of liver enzymes to the same extent as orally given oestrogens, which may have effects on lipid metabolism, hepatic protein synthesis and haemo~tasis~,~. One of the Correspondence: Dr E. Hirvonen, Senior Lecturer, Kalevankatu Medical Center, Kalevankatu 23,00100 Helsinki, Finland. more recent developments in parenteral oestrogen application is an oestradiol gel for transdermal use. The effects of HRT on lipid metabolism have been investigated extensively, but only few investigators have tried to differentiate effects during different phases of sequential oestrogen-progestogen combina- tion~~. In addition, the bone preserving effects of HRT are well known, but research interest has concentrated on the use of the conventional 2 mg dose of oestradiol, with only few reports studying the low-dose alterna- tive~~”. In fact, properly planned dose-finding studies on prevention of osteoporosis are still missing. The objective of this trial was to compare two doses of a new transdermal oestradiol gel plus oral sequential medroxyprogesteroneacetate (MPA) with an oral sequential HRT formulation, studying effects on climacteric symptoms, bleeding control, bone metabolism and lipid profiles. In addition, safety and 0 RCOG 1997 British Journal of Obstetrics and Gynaecology 19