A Review of Transdermal Nonpatch Estrogen Therapy for the Management of Menopausal Symptoms

Abstract

During the transition into menopause, women may experience a wide range of symptoms that negatively impact quality of life. The vasomotor symptoms (VMS) of hot flushes and night sweats are common and vary widely in frequency and severity. The treatment of menopause-associated VMS is a frequently encountered clinical challenge, with the goal of tailoring treatment for each individual woman's needs. Estrogen therapy is the most effective treatment for menopausal VMS. Current guidelines suggest that estrogen therapy be prescribed at the lowest effective dose for the shortest duration of time. Transdermal estrogen therapy has dominated the menopause prescribing practice in Europe for decades; however, in the United States, oral estrogen therapy is most commonly prescribed. Transdermal estrogen therapy can be prescribed at considerably lower doses than oral therapy yet has similar efficacy on the symptoms of menopause. Emerging research demonstrates transdermal estrogen, particularly 17beta-estradiol, may have the potential for fewer health risks than oral estrogen therapy. This review article discusses the spectrum of menopausal symptoms, addresses prevailing issues in the treatment of menopause, elaborates on the risks and benefits of oral and transdermal hormone therapies, and focuses on five nonpatch transdermal estradiol therapies currently available in the United States.

Estrogen neuroprotection and the critical period hypothesis

“…It is also worth mentioning that transdermal E2 has been commonly prescribed for postmenopausal women in Europe for decades, but oral estrogens remain the mainstay of treatment in the U.S. [27]. Transdermal E2 should provide all the benefits of hormone therapy without elevating cardiovascular or neurological disease risk, in accordance with supporting laboratory and clinical E2 cardioprotection and neuroprotection studies.…”

“…Considering this effect, it is no surprise that oral CEEs are associated with increased risks for VTE and ischemic stroke. However, since transdermal E2 bypasses the gut and liver entirely, transdermal HT seems to be a logical, intuitive, and safer option for menopausal women [27, 92, 167, 175]. In fact, as mentioned earlier, the ESTHER study observed a 4-fold increased risk of VTE in oral HT users versus nonusers but no increased risk of VTE in transdermal HT users [25].…”

Evolution of postmenopausal hormone therapy between 2002 and 2009

“…9 By July 2003, 12 months after the initial WHI publication, HT use had decreased between 32% and 38%, 10,17 and by 18 months post-WHI, HT use was nearly 45% below mid-2002 levels. 18 Evolving data affecting the benefit-risk ratio of HT, 19 as well as the continued refinement of menopause treatment guidelines 20,21 and the addition of new therapies to the armamentarium of HT options, 22 may have further altered recent HT utilization. Although data have begun to emerge on physicians' prescribing patterns and opinions of HT post-WHI, no recent long-term evaluation of HT prescription trends in the United States has been published.…”

Endometrial Histology and Safety on Non-Oral Routes of Hormone Therapy for Perimenopausal/Early Menopausal Women: Transdermal Estrogens and Vaginal Micronized Progesterone

“…After closure of the estro-progestogen arm of the WHI (2002), some researchers admitted that not all estrogens and progestogens are alike, and alternative drugs, doses, and delivery systems may exhibit better safety profiles than CEE/MPA (with co-multiple and complex studies of the WHI), with no loss of efficacy [5,6]. The next subchapters will present the transdermal/percutaneous route for estrogens, the vaginal route for micronized progesterone, and the intrauterine systems with levonorgestrel/progesterone for recommendation in menopause transition-early and late perimenopause and early postmenopause from the road of menopause [2].…”