Use of a levonorgestrel-containing intrauterine system with supplemental estrogen improves symptoms in perimenopausal women: a pilot study

Menopause. 2015 Dec;22(12):1301-7. doi: 10.1097/GME.0000000000000557.


Objective: The aim of this study was to compare perimenopausal symptomatology using a levonorgestrel-containing intrauterine system (LNG-IUS) + low-dose transdermal estradiol (TDE) with LNG-IUS alone.

Methods: The trial was a double-blind, randomized, controlled pilot trial. Regularly cycling women aged 38 to 52 years, with at least one self-reported symptom (hot flashes, bloating, headache, adverse mood, or poor sleep), were randomized to either LNG-IUS + low-dose TDE gel (intervention) or LNG-IUS alone (control). TDE was administered once daily as a 0.06% gel containing 0.75 mg of TDE for 50 days. LNG-IUS was placed at least 90 days before TDE or placebo gel treatment to assure stable circulating LNG. Participants completed the Center for Epidemiologic Studies Depression scale (CESD), Hot Flash Related Daily Interference scale (HFRDIS), Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) at the time of LNG-IUS placement, at 90 days (the time of randomization to TDE/placebo), and 140 days (end of study). TDE and placebo groups were compared using repeated-measures analysis of variance.

Results: Thirty-eight women aged 42.9 ± 2.7 years, with a mean BMI of 24.7 ± 3.3 kg/m², were enrolled; 20 were randomized to TDE. Women receiving TDE had significantly improved FSS scores between days 90 and 140 (mean difference TDE: -0.8 ± 1.2 vs placebo: 0.1 ± 0.7; P = 0.026) and borderline significant improvement in HFRDIS scores (mean difference TDE: -5.5 ± 15.3 vs placebo: 4.2 ± 13.1; P = 0.076). Women who reported hot flashes at baseline and who received TDE had a significant decrease in HFRDIS scores between days 90 and 140 (n = 9, P = 0.035). CESD and PSQI scores were not associated with TDE use.

Conclusions: A brief, low-dose estrogen intervention, combined with a LNG-IUS, led to significant improvement of some common perimenopausal symptoms. Such a "minimalist" approach to management of the perimenopause holds promise for reducing common, bothersome perimenopausal symptoms while maintaining effective contraception.

Publication types

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

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Depression / drug therapy
  • Double-Blind Method
  • Estradiol / administration & dosage*
  • Fatigue / drug therapy
  • Female
  • Hot Flashes / drug therapy
  • Humans
  • Intrauterine Devices, Medicated
  • Levonorgestrel / administration & dosage*
  • Middle Aged
  • Perimenopause / physiology*
  • Pilot Projects
  • Placebos
  • Sleep / drug effects
  • Uterus / drug effects*


  • Placebos
  • Estradiol
  • Levonorgestrel