Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women

Climacteric. 2000 Sep;3(3):155-60. doi: 10.1080/13697130008500109.


Background: Transdermal progesterone is being used in some countries as a purported treatment for menopausal symptoms, either alone or prescribed in conjunction with estrogen, but little information exists regarding the biological activity and effectiveness of this method of delivery of progesterone in protecting the endometrium from excess proliferation. This study was designed to evaluate the use of sequential transdermal progesterone. End-points evaluated included endometrial cellular response and bleeding pattern as well as plasma hormone levels and salivary progesterone estimations.

Method: Twenty-seven postmenopausal women were treated with continuous transdermal estrogen (28-day cycle) and a cream containing 16, 32 or 64 mg of progesterone in each 4-cm extrusion from a tube of Pro-Feme administered daily in a sequential (days 15-28 of cycle) regimen. Blood and endometrial samples were analyzed for progesterone response prior to therapy, after the first 14 days of unopposed transdermal estrogen and following 14 days of transdermal progesterone. Saliva samples were taken during the last 14 days of the 84-day study, when the final progesterone cream therapy was being applied.

Results: Hormone assay indicated that physiological levels of estradiol were achieved, but progesterone levels were insufficient to induce any detectable change in the endometrium. Only one patient experienced bleeding during the study period. Levels of salivary progesterone were so variable as to be considered completely unreliable in determining the potential influence on biological activity.

Interpretation: Pro-Feme transdermal progesterone administered in a 16-, 32- or 64-mg daily dose for 14 days in a sequential regimen does not appear to be effective in inducing a secretory change in a proliferative endometrium. Salivary progesterone levels were not of value in managing the therapy of postmenopausal women.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Biopsy
  • Cell Division / drug effects
  • Endometrium / cytology
  • Endometrium / drug effects*
  • Estradiol / administration & dosage
  • Estradiol / blood
  • Estrogen Replacement Therapy
  • Female
  • Humans
  • Postmenopause*
  • Progesterone / administration & dosage*
  • Progesterone / analysis*
  • Progesterone / blood
  • Saliva / chemistry*
  • Uterine Hemorrhage / epidemiology*


  • Progesterone
  • Estradiol