Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other outcomes over 52 weeks of therapy

Abstract

Background Continuous combined hormone replacement therapy (HRT) with 0.5 mg 17β-estradiol (E2) + 0.1 mg norethisterone acetate (NETA) received marketing approval based on 24-week results. The current study collected data up to 52 weeks, including consideration of bleeding, a major reason for stopping HRT.

Methods This 52-week (13 lunar-month), non-interventional, prospective study involved 169 women from Norway and Sweden receiving daily oral 0.5 mg E2 + 0.1 mg NETA to treat menopausal symptoms. Incidences and cumulative rates of amenorrhea (no bleeding or spotting) and no bleeding (women could have spotting) were evaluated, together with hot flushes and quality of life.

Results Overall, > 78% and > 90% of subjects were amenorrheic or had no bleeding, respectively, in each of the first 3 lunar months, while > 88% and > 96% were amenorrheic or had no bleeding, respectively, in each of lunar months 10, 11 and 12. Cumulative rates of amenorrhea and no bleeding were 67% and 83%, respectively, in lunar months 1–3, and 84% and 94%, respectively, in lunar months 10–12. The number of hot flushes declined during treatment (means at weeks 1, 12 and 52, respectively: 15.5, 5.0 and 4.1 [mild]; 19.0, 3.0 and 2.3 [moderate]; 10.8, 1.1 and 0.9 [severe]). Improvement in all four domains of the Menopause-Specific Quality of Life-Intervention questionnaire (vasomotor, psychosocial, physical and sexual) was evident by week 26.

Conclusion For women receiving 0.5 mg E2 + 0.1 mg NETA, lack of bleeding-related side-effects, together with beneficial effects on hot flush symptoms and quality of life, may promote treatment continuance.

Key words::

• BLEEDING
• CONTINUOUS COMBINED HORMONE REPLACEMENT THERAPY
• ESTRADIOL
• HOT FLUSHES
• MENOPAUSE
• NORETHISTERONE ACETATE
• QUALITY OF LIFE
• ULTRA-LOW-DOSE

ACKNOWLEDGEMENTS

The authors would like to thank the other investigators. Norway: Dr Terje Sørdal, Dr Stig Pedersen, Dr Erling Ekerhovd, Dr Ingrid M. Ringen, Dr Bjarne Christian Eriksen, Dr Åsle Marit Ullern, Dr Kari-Anne Trosterud, Dr Oddvar Sviggum, Dr Anne Zandjani, Dr Anette Berg, Dr Inger Øverlie, Dr Knut Hesla, Dr Deirdre Nsubuga, Dr Anne-Cecilie Hallquist, Dr Martin Andresen, Dr Nina Willumsen, Dr Kathe Aase, Dr Merete Blakstad, Dr Heidi Høgdahl, Dr Karen Time, Dr Rune Mork Braut, Dr Berit Aune, Dr Tone Årmot Jareld. Sweden: Dr Björn Andersch, Dr Anders Barth, Dr Anders C:son Roth, Dr Katarina Hellgren, Dr Agneta Ehrenborg, Dr Maria Olsson, Dr Ted Mingelgrin, Dr Margareta Fredstorp, Dr Heidi Amdahl.

Medical writing support for this manuscript was provided by Andy Lockley of Bioscript Medical and funded by Novo Nordisk A/S.

Conflict of interest L-Å. Mattsson, H. E. Ipsen and C-J. Granqvist report no conflicts of interest. M. Kokot-Kierepa is an employee of Novo Nordisk Region International Operations AG, Switzerland.

Source of funding The study was supported by Novo Nordisk A/S.