Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk

Anticancer Drugs. 2014 Aug;25(7):745-50. doi: 10.1097/CAD.0000000000000050.


Combined hormonal contraceptives (CHCs) contain estrogen and progestin, which can stimulate estrogen-sensitive and/or progesterone-sensitive breast cancer growth. Until recently, ethinylestradiol had been almost the only estrogen used for decades, and its dose has been greatly reduced over time. The first generations of birth control pills contained approximately five times more estrogen and four times more progestin than the latest contraceptives. Newer CHCs also contain steroids that more closely mimic the physiological estradiol (E2) and progesterone effects. The newer CHC formulations are thus expected to have less influence on the breast, although it is very difficult to demonstrate any difference among the recent available preparations in human studies. Recently, nomegestrol acetate (NOMAC), a neutral, nonandrogenic, progesterone-like profile progestin, has become available in combination with the 'natural' estrogen, E2. According to the literature, NOMAC/E2 is expected to have either a lesser stimulating effect or a neutral effect on estrogen-sensitive breast cancers. We performed an analysis of the available studies and a bibliographical review. The endocrine and metabolic effects of NOMAC/E2 formulation might lead to a lesser breast tissue stimulation. The data reported, confirmed through clinical studies, should be considered when choosing a hormonal contraceptive, especially when breast stimulation is a concern.

Publication types

  • Review

MeSH terms

  • Breast / drug effects
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / prevention & control*
  • Cell Proliferation / drug effects
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Estradiol / adverse effects*
  • Female
  • Humans
  • Megestrol / adverse effects*
  • Membrane Proteins / metabolism
  • Neoplasms, Hormone-Dependent / chemically induced
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / prevention & control
  • Norpregnadienes / adverse effects*
  • Receptors, Progesterone / metabolism
  • Risk


  • Contraceptives, Oral, Hormonal
  • Membrane Proteins
  • Norpregnadienes
  • PGRMC1 protein, human
  • Receptors, Progesterone
  • Estradiol
  • nomegestrol acetate
  • Megestrol