Drugs Approved by the FDA

The following information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: BioSante
Approval Status: Approved December 2006
Treatment for: Vasomotor symptoms associated with menopause

General Information

Elestrin (estradiol gel) is a gel formulation of estradiol (the bio-identical human estrogen) designed to be absorbed through the skin after application on the arms, shoulders, thighs or abdomen, delivering estradiol to the blood stream evenly over time in a non-invasive and painless manner. Estrogens are secreted by a woman's ovaries and are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. The ovaries stop making estrogens when a woman is between the ages of 45 and 55. This drop in estrogen levels causes the symptoms commonly seen in menopause, including hot flashes.

Elestrin is specifically indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause.

Elestrin is supplied as a hydroalcoholic gel for topical administration. The recommended initial dose of the drug is one pump per day or (0.87 g/day, which contains 0.52 mg of estradiol). The dose may be escalated based on individual response.

Clinical Results

FDA Approval
FDA approval of Elestrin was based on the results of a phase III trial evaluating Elestrin in the treatment of vasomotor symptoms associated with menopause. This randomized, double-blind, placebo-controlled trial enrolled 484 postmenopausal women between 28 and 74 years of age who had at least 60 moderate-to-severe hot flushes per week at baseline. Subjects applied placebo, Elestrin 0.87 g (0.52 mg estradiol), 1.7 g (1.02 mg estradiol), or 2.6 g (1.56 mg estradiol) once daily to the upper arm for 12 weeks. Statistical significance was seen in both the frequency and severity of hot flash symptoms in the Elestrin 1.7 g/day treatment group when compared to placebo at week four (P<0.0001) and week 12 (P<0.001). Elestrin 0.87 g/day reached statistical significance at week 12 versus placebo (P<0.0001).

Side Effects

Adverse events associated with the use of Elestrin may include, but are not limited to, the following:

• Nasopharyngitis
• Breast Tenderness
• Metrorrhagia
• Upper Respiratory Tract Infection
• Nausea
• Vaginal Discharge
• Nipple Pain
• Endometrial Hyperplasia

  In addition, Elestrin was shown to cause elevated blood pressure, hypertriglyceridemia, impaired liver function, hypothyroidism, fluid retention, hypocalcemia, ovarian cancer, exacerbation of endometriosis and other conditions, photosensitivity and photoallergy. Finally, Estradiol absorption was increased when sunscreen was applied 10 minutes before Elestrin application. Sunscreen should not be applied to the same site until at least 25 minutes after the application of Elestrin.

  Mechanism of Action

  Elestrin delivers estradiol (a bio-identical human estrogen) to the blood stream evenly over time in a non-invasive and painless manner. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. They are secreted by a woman's ovaries and are responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. The ovaries stop making estrogens when a woman is between the ages of 45 and 55. This drop in estrogen levels causes the symptoms commonly seen in menopause, including hot flashes. Elestrin application raises the circulating estrogen levels thus relieving the vasomotor symptoms of menopause.

  Literature References

  Fonseca AM, Bagnoli VR, Penteado SR, Paixao JS, Cavalcanti AL, Pinotti JA Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women. Clinical drug investigation 2007;27(2):131-7.

  Schmidt JW, Wollner D, Curcio J, Riedlinger J, Kim LS Hormone replacement therapy in menopausal women: Past problems and future possibilities. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2006 Oct;22(10):564-77.

  Simon JA; ESTRASORB Study Group Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms. Menopause (New York, N.Y.) 2006 Mar-Apr;13(2):222-31

  Archer DF; EstroGel Study Group Percutaneous 17beta-estradiol gel for the treatment of vasomotor symptoms in postmenopausal women. Menopause (New York, N.Y.) 2003 Nov-Dec;10(6):516-21.

  Moses-Kolko EL, Berga SL, Greer PJ, Smith G, Cidis Meltzer C, Drevets WC Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Fertility and sterility 2003 Sep;80(3):554-9.

  Additional Information

  For additional information regarding Elestrin or vasomotor symptoms associated with menopause, please visit the Elestrin web page.