Low-dose transdermal estrogen viable short-term treatment for menopausal women

Alternative hormones, doses and delivery systems not explored in WHI may exhibit

Low-dose transdermal hormone therapy (HT) remains a viable short-term alternative for women to treat debilitating menopausal symptoms, offer lipid protection and preserve bone health, despite the negative news about oral HT effects from the Women’s Health Initiative (WHI), according to a recent review of peer-reviewed medical studies by Mary Jane Minkin, M.D., of Yale University School of Medicine, in the April The Journal of Reproductive Medicine.

“There is a lot to consider when interpreting the WHI results. The fact is that millions of women still suffer from the potentially devastating symptoms of menopause – so much so that their quality of life deteriorates. Hormone therapy remains the most effective means to relieve vasomotor symptoms, and certain estrogen formulations and routes of administration that were not studied in WHI offer different health effects that may offer several advantages,” said Dr. Minkin, clinical professor in the Department of Obstetrics and Gynecology at Yale.

Unexpected results from the WHI published in June 2002 called into question the safety of all HTs – even though investigators only examined oral HTs that used conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). The researchers cautioned that the WHI results did not necessarily apply to other doses of CEE/MPA, to other types of oral estrogens and progestins, or to other estrogens and progestins delivered by different routes.

“Reproductive healthcare professionals may find it difficult to counsel their patients who suffer from severe menopausal symptoms about appropriate treatment because not all estrogens and progestins are alike. Alternative drugs, doses and delivery systems may exhibit better safety profiles than CEE/MPA formulations, with no loss of efficacy,” Dr. Minkin noted.

Transdermal, unlike oral, HT delivery bypasses the liver, permitting the use of estrogen doses that are substantially less than in pills, thereby reducing the risk of certain adverse effects while providing benefits, according to the review. Transdermal formulations of the transdermal estradiol (E2) offer relief of such menopausal symptoms as hot flashes, night sweats and disturbed sleep that affect patients’ quality of life.

Moreover, the use of transdermal E2 offers protection against two heart-damaging lipids by decreasing levels of low-density lipoprotein (LDL) cholesterol and triglycerides. Both lipids play a role in the development of metabolic syndrome, which becomes more common in women as they age, particularly after the onset of menopause. The syndrome is associated with an increased risk for heart disease and is a major predictor of type 2 diabetes.

“When women with the metabolic syndrome require HT for the relief of their vasomotor symptoms, transdermal E2 can provide the additional benefit of decreasing both LDL cholesterol and triglyceride levels significantly lower than those achieved with oral HTs. In fact, oral estrogen can produce an initial increase in triglycerides, before achieving moderate lipid decreases, ” said Dr. Minkin.

Additionally, unlike oral CEE, which causes a substantial increase in C-reactive protein (CRP), transdermal E2 shows no increase in CRP. CRP is a sensitive marker of inflammation associated with an increased risk of heart attacks and strokes. Transdermal E2 also builds bone mass density, which could benefit women at risk for osteoporosis.

Recent guidelines issued by the American Association of Clinical Endocrinologists and the North American Menopause Society recommend the use of transdermal estrogen, rather than oral HT, for women with high triglyceride levels. The U.S. Food and Drug Administration advises women who decide that HT is appropriate to use the lowest effective dose for the shortest duration to reach their treatment goals.

Menopause
Menopause is a natural part of a woman’s life that occurs when menstruation stops permanently, on average at age 51. During menopause, the ovaries reduce their production of the hormones estrogen, progesterone and androgen.

About 75 percent of menopausal women report troublesome symptoms–which can become severely debilitating in up to 20 percent: including heart palpitations, hot flashes, night sweats, headaches, mood swings, anxiety, irritability, loss of vaginal lubrication, changes in sexual functioning, numbness, tingling, fatigue, increase in urinary problems, memory loss, weight gain and dry eyes and mouth. Also, the menopausal decline in hormone levels can have potential long-term consequences not immediately apparent, such as increased risk for osteoporosis and coronary heart disease.