Chwalisz K, Perez MC, Demanno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005;26:423–438.
In this comprehensive review, the authors draw from their extensive expertise in endocrinology to describe the rationale behind asoprisnil, a mixed progesterone receptor agonist/antagonist—the most promising pharmaceutical development in gynecology in several decades.
How the drug works
Mifepristone (RU-486) was the first progesterone receptor antagonist. Despite its ability to reduce myoma volume and suppress endometriosis symptoms in small pilot studies, it induces endometrial hyperplasia at doses higher than 5 to 10 mg, probably by acting similarly to unopposed estrogen. In contrast, asoprisnil has antiproliferative effects and no labor-inducing activity. It directly affects blood vessels in the endometrium, creating a local antiproliferative effect that induces amenorrhea despite normal estrogen levels.
What phase II studies reveal
A multicenter, double-blind, placebo-controlled trial involved 5-, 10-, and 25-mg daily doses of oral asoprisnil over 12 weeks. In a dose-dependent manner, asoprisnil induced amenorrhea or significantly suppressed bleeding without causing breakthrough or intermenstrual flow. It also decreased the volume of both the largest fibroid and the uterus as a whole. At 10- and 25-mg doses, pressure symptoms eased substantially over placebo. Adverse effects were minimal and affected the placebo and asoprisnil groups equally.
Phase III trials are now under way to assess the safety and efficacy of asoprisnil in the treatment of menorrhagia and uterine fibroids. Early results in the treatment of endometriosis are also promising.
What this means for fibroid patients
Though asoprisnil is not yet available for use, the phase III trial is winding down and the drug’s impressive potential seems clear.
A useful strategy may be to counsel marginally symptomatic women with fibroids that treatments are in the pipeline that would permit pharmaceutical management of their symptoms. Because this drug induces amenorrhea in the presence of normal circulating estrogen levels, it eliminates hot flushes and, more importantly, the bone loss associated with gonadotropin-releasing hormone agonists.
Disclosure
The author reports no financial relationships relevant to this article.