Optimal tolerability of ultra-low-dose continuous combined 17β-estradiol and norethisterone acetate: laboratory and safety results

Abstract

Objective To evaluate the influence of two ultra-low doses of oral continuous combined hormone therapy and placebo on metabolic parameters, and to assess safety endpoints and overall tolerability in healthy postmenopausal women.

Design In a subpopulation of the Clinical study on Hormone dose Optimisation In Climacteric symptoms Evaluation (CHOICE) trial, lipids and parameters of glucose metabolism and hemostasis were analyzed in Nordic women (n = 158) at baseline and after 12 and 24 weeks of treatment with 0.5 mg 17β-estradiol (E2) + 0.25 mg norethisterone acetate (NETA), 0.5 mg E2 + 0.1 mg NETA or placebo. Adverse events occurring from the first trial-related activity, whether related or not related to the study medication, were recorded for the entire population (n = 575) of the trial. The seriousness, relationship to treatment and the reason for withdrawal were reported.

Results Both ultra-low-dose combinations were neutral to changes in lipid and lipoprotein, hemostasis parameters and carbohydrate metabolism during the trial. The incidence of serious adverse events was only 1% in respective treatment groups. Adverse events were the reason for withdrawal in only 2% and 6% of women in the 0.5 mg E2 + 0.25 mg and 0.1 mg NETA groups, and in 8% in the placebo group. No weight gain or change in blood pressure was reported during the trial in any of the study groups.

Conclusion The treatments had neutral effects on metabolic parameters in the study population. Excellent tolerability of both ultra-low doses resulted in high completion rates.

Key words:

• MENOPAUSE
• TOLERABILITY
• METABOLIC PARAMETERS
• ULTRA-LOW DOSE
• ESTRADIOL
• NORETHISTERONE ACETATE

Acknowledgements

CHOICE Principal Investigators: Abrahamasson L-O, Denmark; Bieler V, Switzerland; Blagden M, UK; Blanc B, France; Boschitsch E, Austria; Burgener L, Switzerland; Chef R, Belgium; Christau S, Denmark; Christoffersen C, Denmark; Damm S, Sweden; Depypere H, Belgium; Durand G, France; Dutchman D, UK; Eckrich R, Germany; Engebretsen T, Norway; Everett M, UK; Fardellone P, France; Farquarson R, UK; Fehr M, Switzerland; Felding C, Denmark; Gray S, UK; Hammar M, Sweden; Hellberg E, Sweden; Hillard T, UK; Huber J, Austria; Ingelhammar E, Sweden; Karinen L, Finland; Keil D, Germany; Keyser J-L, Belgium; King H, UK; Kingston F, UK; Kohoutek U, Germany; Koninckx P, Belgium; Léonard D, Belgium; Lilleeidet O, Norway; Lopes P, France; Lundgren R, Norway; Mattsson L-Å, Sweden; Maurer E, Switzerland; Maxwell T, UK; Moeller B, Denmark; Morris E, UK; Mortensen O, Norway; Mueck A, Germany; Naessen T, Sweden; O'Brien S, UK; Ofjord E, Norway; Panay N, UK; Peen A, Denmark; Peters Lingman E, Sweden; Piippo S, Finland; Pinitiaux A, Belgium; Pitkin J, UK; Pittner B, Germany; Pornel B, Belgium; Rantala M-L, Finland; Rasmussen H, Denmark; Rees RM, UK; Riis-Johannesen G, Norway; Rosenberg S, Belgium; Roy F, UK; Rymer J, UK; Salzmann C, France; Samsioe G, Sweden; Saul P, UK; Schmid E, Switzerland; Schönberg L, Germany; Schönian S, Germany; Seif M, UK; Skouby S, Denmark; Smets M, Belgium; Smith C, UK; Smithers A, UK; Solbakken H, Norway; Sordal T, Norway; Strang S, UK; Sturdee D, UK; Thelen H, Germany; Varila E, Finland; Wallhäusser T, Germany; Walling M, UK; Whitehead M, UK; Wojtasinska M, Norway; Wright A, UK; Yikorkala O, Finland; Zimmermann H, Germany.

Conflict of interest Göran Samsioe has received honoraria for consulting and for lectures from Novo Nordisk FemCare AG, Wyeth, Pfizer, Eli-Lilly, Novartis. Josef Hruska is an employee of Novo Nordisk FemCare AG.

Source of funding This research was supported by Novo Nordisk A/S, Zurich, Switzerland.