Pharmacology Update

Estradiol/Levonorgestrel Transdermal System (Climara ProTM)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved the first once-a-week combined hormone therapy for postmenopausal symptoms. This transdermal system delivers estradiol and the progestin levonorgestrel, which until now has only been used in contraceptive combinations. Berlex markets transdermal estradiol/levonorgestrel as Climara ProTM.


Estradiol/levonorgestrel (E2/LNG) is indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.1


One transdermal system is applied to a smooth, clean area of the skin on the lower abdomen. The system should be replaced weekly. The sites should be rotated with an interval of at least 1 week between applications to the same site. If the system falls off it can be reapplied to another site on the lower abdomen. If a new system is needed the original treatment schedule should be maintained.1 Each system delivers 45 mg/d of estradiol and 15 mg/d of levonorgestrel.

Potential Advantages

E2/LNG provides a convenient once-weekly hormone treatment for menopausal symptoms (ie, hot flushes) with a progestin to protect against endometrial hyperplasia.

Potential Disadvantages

E2/LNG is not approved for the treatment of vulvar and vaginal atrophy. Application site reactions are the most common adverse effects (40.6%). In controlled clinical trials, 2.1% of participants withdrew from treatment at 12 weeks and 8.5% at 1 year. Other side effects include vaginal bleeding (36.8%) and breast pain (18.9%).1


E2/LNG has been shown to reduce the number and severity of moderate-to-severe hot flushes compared to placebo.1,2 In addition, over a 1-year period, E2/LNG did not show any significant endometrial hyperplasia. In contrast, 17% of subjects on E2 alone (ClimaraTM) showed hyperplasia.1,2 The cumulative proportion of patients with uterine bleeding or spotting was lower with E2/LNG compared to E2 alone.2 Triglyceride levels declined compared to E2 alone. Application site reactions, vaginal bleeding, and breast pain were the most common side effects. The wholesale cost of Climara ProTM is $30.50 per month which is higher than ClimaraTM ($28).

Clinical Implications

E2/LNG is the first once-weekly patch for treating moderate-to-severe vasomotor symptoms. Another product, estradiol/norethindrone acetate (CombiPatchTM) is applied twice weekly. As a result of the WHI study, estrogen or estrogen/progestin products may be considered for moderate-to-severe vasomotor symptoms and should be used at the lowest dose for the shortest duration possible. E2/LNG provides another option for this use. Transdermal estrogen appears to be associated with a more favorable risk/benefit ratio compared to oral estrogen in regards to thrombotic, hemodynamic, and endothelial effects.3,4  

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.


1. Climara ProTM Product Information. Berlex. December 2003.

2. Shulman LP, et al. Menopause. 2002;9(3):195-207.

3. Girdler SS, et al. Obstet Gynecol. 2004;103(1):169-180.

4. Scarabin PY, et al. Lancet. 2003;362:428-432.