Brand Name Drug: Ortho-Prefest
Active Ingredient Drug: 17(beta)-estradiol / norgestimate
Indication: Treatment of vasomotor symptoms associated with menopause, treatment of vulvar and vaginal atrophy, and prevention of osteoporosis
Company Name: Ortho-McNeil Pharmaceuticals
Availability: Approved for marketing in the US on October 22, 1999
A variety of types of hormone replacement therapy (HRT) are available for women who are experiencing symptoms of menopause, particularly hot flashes and vaginal atrophy. HRT has also been shown to reduce the risk of osteoporosis and heart disease. Now a new form of HRT has been approved with a once-a-day dosing schedule that will enhance patient compliance: Ortho-Prefest. Manufactured by Ortho-McNeil Pharmaceutical, a division of Johnson & Johnson, Ortho-Prefest contains 17-beta-estradiol and norgestimate combined in a single tablet.
The tablet containing 1.0 mg estradiol is taken on days 1-3 of therapy, and the tablet containing 1.0 mg estradiol plus 0.09 mg norgestimate is taken on days 4-6. The pattern is then repeated continuously to produce a constant estrogen/intermittent progestogen regimen. Ortho-Prefest is indicated for the treatment of vasomotor symptoms of menopause (hot flashes) and vulvar and vaginal atrophy, and for the prevention of osteoporosis.
How It Works
Estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites. Circulating estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle stimulating hormone through a negative feedback mechanism, and estrogen replacement therapy acts to reduce the elevated levels of these hormones in postmenopausal women.
Norgestimate is a derivative of 19-nortestosterone and behaves similar to natural progesterone. Progestins counter estrogenic effects by decreasing the number of nuclear estradiol receptors and suppressing epithelial DNA synthesis in endometrial tissue.
Ortho-Prefest: Clinical Study Results
Ortho-Prefest was evaluated in two 12-month trials in 1,212 healthy postmenopausal women. The results showed that Ortho-Prefest reduced the mean number of daily hot flashes from 10.9 at baseline to 0.7 at week 12; the corresponding numbers for estrogen alone were 11.0 and 1.1, respectively. When assessed for its effect on vulvar and vaginal atrophy, Ortho-Prefest was associated with a 31.9% decrease in the percentage of parabasal cells, an increase of 16.7% in intermediate cells, and an increase of 15.2% in superficial cells; the corresponding values for estrogen alone were -22.4%, 7.2%, and 15.3%, respectively.
The incidence of endometrial hyperplasia in women treated with Ortho-Prefest was 0%, while 29% of women who receive estrogen alone have some degree of hyperplasia. The percentage of women with cumulative amenorrhea during the 12-month trial period ranged from 24% at baseline to 51% at 12 months; the corresponding values for estrogen alone were 39% and 63%, respectively. Finally, Ortho-Prefest was associated with a 1.9% reduction in total cholesterol, a 9.7% increase in HDL-cholesterol, a 1.2% increase in LDL-cholesterol, and a 9.4% increase in triglycerides; the corresponding values for estrogen alone were 1.2%, 12.0%, 1.7%, and 29.0%, respectively.
What the Patient Should Know
The most commonly reported adverse effects associated with Ortho-Prefest were headache, breast pain, and upper respiratory infection. Others included back pain, flu-like symptoms, and abdominal pain. Because hormone replacement therapy has been associated with cancers of the breast and endometrium, as well as venous thromboembolism and gallbladder disease, a woman should speak to her healthcare provider and carefully consider her medical history before embarking on hormone replacement therapy such as Ortho-Prefest.