The second clinical trial (Trial 2) was a 12-week randomized, double-blind and placebo-controlledtrial that enrolled 558 generally healthy postmenopausal women between 40 to 80 years of age (mean years) who, at baseline, had identified moderate to severe dyspareunia as their most bothersome symptom of vulvar and vaginal atrophy. In addition to dyspareunia, women had ≤ 5% superficial cells on vaginal smear and a vaginal pH > 5. Women were randomized in a 2:1ratio to receive once daily vaginal insert mg INTRAROSA (n=376)or placebo (n=182).The primary endpoints and study conduct were the same or similar to those in Trial 1.
Aromatase inhibitor drugs (patent pharmaceuticals) are “approved” for estrogen receptor positive (ER+) early breast cancer and following Tamoxifen therapy. They include Aromasin ® (exemestane), an irreversible steroidal inhibitor; Femara ® (letrozole) and Arimidex ® (anastrozole), which are non-steroidal inhibitors. Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women, since the decrease in estrogen stimulates androgen production by the ovaries, which will counteract their effect. The most common side effects of aromatase inhibitors are joint stiffness or joint pain. Regular bone density testing is recommended for those taking aromatase inhibitor drugs. 23-25
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.