Symptoms arising from female reproductive organ dysfunction constitute the second most common reason for subjects to present to primary care providers. Conditions such as infertility, endometriosis, dysmenorrhea and menopause are very common in female subjects all over the world. In the U.S., data on the incidence and prevalence of four common disorders of reproductive health are as follows:

Condition	Prevalence (US)
Infertility	6 million couples
Endometriosis	5 million women (7% of women of childbearing age)
Dysmenorrhea	Very common (13 - 28% of women of childbearing age)
Menopause	36 million women (expected incidence over next decade)
Fibrocystic Breast Disease	Approximately 30% of women between ages 30-50 and 50% of women of all ages

Practicing clinicians face challenges in the optimal management of conditions such as infertility, menopause and endometriosis. Reasons for this include the chronic nature and high prevalence of these diagnoses in the average practice, the need for intense monitoring of treatment regimens and the presence of rapidly evolving data as new drugs are being generated in pharmaceutical pipelines. Furthermore, the data generated from clinical studies is at times conflicting, further confounding the ability of clinicians to confidently direct therapy in optimal directions.

One of the most active areas of research is the development of therapies aimed at improving the quality and length of life in older menopausal women. The Women's Health Initiative (WHI) was established by the National Institutes of Health in 1991 and presents a national health study that focuses on strategies for the prevention of heart disease, breast and colorectal cancers, and osteoporosis in postmenopausal women. The WHI is a 15-year project involving 161,000 women ages 50 to79. This study will attempt to provide practical information to women and their physicians about the risks and benefits of hormone-replacement therapy.

Currently, there are multiple clinical trials in progress for the evaluation of hormonal therapies in menopause. Many of the trials involve new formulations of already approved drugs (example, transdermal preparations) as well as the use of testosterone as an adjunct in hormone replacement therapy; trials that involve the evaluation of new molecular entities that can be used for hormone replacement therapy are very few.

In the field of infertility, Serono Laboratories has a number of clinical trials evaluating the use of recombinant hormones as well as hormone antagonists in the treatment of female infertility. Luveris, a recombinant human luteinizing hormone (r-hLH), is approved in Europe for the treatment of female infertility and is undergoing phase II and III trials in the U.S. for this indication.

For women with endometriosis - a condition of unknown etiology that causes chronic pelvic pain and infertility - several drugs are undergoing clinical trials. These include gonadotropin-releasing hormone (GnRH) agonists (such as Leuprolide - in a formulation that can be inhaled), luteinizing hormone antagonists (such as Abarelix) and aromatase inhibitors (such as Yamanouchi's YM-511). Two other drugs, both GnRH antagonists, have potential in the treatment of endometriosis. Ganirelix: Antagon/Organon; Cetrorelix: Cetrotide/Serono are not currently in clinical trials, but preliminary data suggest potential efficacy with fewer side effects than currently approved regimens. These two drugs have both been approved by the FDA for the treatment of infertility in female subjects.

Finally, in the area of fibrocystic breast disease (FBD), Symbollon Pharmaceuticals is testing Iogen, an oral pill containing molecular iodine. Iogen acts to stimulate the body to metabolize estrogen more quickly, resulting in lower levels of estrogen in the blood. This reduces breast estrogen receptor stimulation, resulting in reduced symptoms of breast pain and tenderness. Phase I and II trials have shown positive results and the company plans to proceed with pivotal phase III trials involving approximately 1,500 subjects. If significant improvement in symptoms and signs of FBD is documented in these phase III trials, Iogen would represent a marked improvement over currently available treatments.

In summary, the management of disorders affecting the reproductive health of women is evolving with several potential therapies in the drug development pipeline. In light of the fact that the conditions described above affect a large proportion of the female population, newly approved therapies that demonstrate high efficacy with a low incidence of side effects would offer a competitive edge over current therapies.