Advances in Therapy

, Volume 25, Issue 6, pp 525–551

Rationale for low-dose systemic hormone replacement therapy and review of estradiol 0.5 mg/NETA 0.1 mg


DOI: 10.1007/s12325-008-0070-6

Cite this article as:
Johansen, O.E. & Qvigstad, E. Adv Therapy (2008) 25: 525. doi:10.1007/s12325-008-0070-6


The menopausal transition is associated with several symptoms, for which both non-pharmacological and pharmacological measures are available to provide relief. However, present knowledge indicates that the former is not highly effective, and that the latter, in terms of systemic oestrogen and progestogen-based hormone replacement therapy (HRT), although being effective (e.g. on vasomotor symptoms, bleeding control, bone mineral density, vaginal atrophy and quality of life), can be associated with some caveats. Amongst these are an increased risk for coronary heart disease, breast cancer, venous thromboembolism and stroke.

In recent years, literature has indicated a dose dependency for HRT on some of the caveats, hence authorities (Food and Drug Administration, and the European Medicines Agency) and menopause societies (International Menopause Society and North American Menopause Society) now recommend that women deemed in need of HRT should receive the lowest possible dose without compromising the effect of symptom relief. Estradiol 0.5 mg/norethisterone acetate (NETA) 0.1 mg, despite being a lower dose than conventional hormones, is a compound, among a few other low-dose options, that can be used in such therapy. As a first-line oral option, it has demonstrated its effectiveness (which seems comparable to other compounds), with high tolerability and, apparently, no safety concerns, in a 6-month study. Further long-term clinical trials and observational studies are mandatory in order to capture any potential harm as well as to elucidate this compound’s full potential.

Following a thorough literature search using PubMed and MEDLINE from the earliest publication dates through to January 2008, including results from various types of clinical trials and statements on HRT, we review the rationale for these recommendations. We also review the effects and safety of a novel ‘ultra-low-dose’ oral continuous combined HRT tablet, estradiol 0.5 mg/NETA 0.1 mg.


cardiovascularHRTmammographic densitymenopauseNETAoestrogenpharmacological treatmentprogestogenrandomised controlled trialsreview

Copyright information

© Springer Healthcare Communications 2008

Authors and Affiliations

  1. 1.Medical departmentAsker and Baerum HospitalRudNorway
  2. 2.Department of GynaecologyUllevål University HospitalOsloNorway