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Norethisterone and its acetate – what’s so special about them?
  1. Emilia Huvinen,
  2. Elina Holopainen,
  3. Oskari Heikinheimo
  1. Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki 00029, Finland
  1. Correspondence to Dr Emilia Huvinen, Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki 00029, Finland; emilia.huvinen{at}helsinki.fi

Abstract

Introduction Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis. Norethisterone (NET) and its acetate (NETA) differ from other progestogens by their partial conversion to ethinylestradiol (EE). We review their special characteristics and focus on the clinically relevant risk factors associated with estrogen action, such as migraine with aura and risk of thrombosis.

Methods Narrative review based on a medical literature (OvidMedline and PubMed) search.

Results NET converts to significant amounts of EE; 10–20 mg NET corresponds to 20–30 µg EE. The effects of NET on the endometrium are pronounced, making it a good choice for treating abnormal uterine bleeding, endometriosis, and endometrial hyperplasia. NET also has beneficial effects on bone mineral density and positive or neutral effects on cardiovascular health. Conversely, long-term use of NET is associated with a slightly increased breast cancer risk, and the risk of venous thromboembolism is moderately increased. This risk seems to be dose-dependent; contraceptive use carries no risk, but therapeutic doses might be associated with an increased risk. Studies suggest an association between combinations of EE and progestogens and ischaemic stroke, which in particular concerns women with migraine. No studies have, however, assessed this risk related to the therapeutic use of NET.

Conclusions NET is a potent progestogen, especially when considering the endometrium. Its partial conversion to EE, however, is important to remember. Clinical consideration is required with women at high risk for either breast cancer or thromboembolism, or experiencing migraine with aura.

  • hormonal contraception
  • general practice
  • intrauterine devices
  • menopause
  • oral contraceptives
  • pharmacoepidemiology
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Footnotes

  • Twitter @e_huvinen

  • Contributors EmH participated in planning the study, performing the literature search, as well as drafting, writing, and editing the article. ElH participated in planning the study, helped with the literature search, and participated in drafting and editing the article. OH helped with the literature search and participated in drafting and editing the article. All authors have approved the final version of the manuscript, and EmH submitted the work on behalf of all the authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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