U.S. Census Bureau estimates. B: Age-and race-specific incidence of hysterectomy for fibroids, 1997, based on NIS and U.S. Census Bureau estimates. (From Health Services/ Technology Assessment Tests (HSTAT). Available at http://www.ncbi.nlm.nih.gov/books/ bv.fcgi?rid=hstat1.section.48317.)
Serum levels of estrogen and progesterone are similar in women with and without clinically detectable fibroids. However, as a result of increased levels of aromatase within fibroids, de novo production of estradiol is higher than in normal myometrium (12). Progesterone is important in the pathogenesis of fibroids, which have increased concentrations of progesterone receptors A and B compared with normal myometrium (13,14). The highest mitotic counts are found in fibroids at the peak of progesterone production (15). Gonadotropin-releasing hormone (GnRH) agonists decrease the size of fibroids, but progestin given concurrently with GnRH prevents a decrease in size (14).
Human fibroid tissue, grafted to immunodeficient mice, increased in size in response to estradiol plus progesterone, but the growth was blocked by the antiprogestin RU486 (16). The volume of grafted fibroid tissue decreased after progesterone withdrawal. Treatment with estradiol alone did not increase the graft size, but did induce expression of progesterone receptors and supported the action of progesterone on the grafts (16).
For the majority of postmenopausal women with fibroids, hormone therapy will not stimulate fibroid growth. If fibroids do grow, progesterone is likely to be the cause (32). One study evaluated postmenopausal women with fibroids who were given 2 mg of oral estradiol daily and randomized to 2.5 or 5 mg of medroxyprogesterone acetate (MPA) per day (32). One year after starting treatment, 77% of women taking 2.5 mg MPA had either no change or a decrease in fibroids diameters and 23% had a slight increase. However, 50% of women taking 5 mg MPA had an increase in fibroid size (mean diameter increase of 3.2 cm).
Postmenopausal women with fibroids treated with 0.625 of conjugated equine estrogen (CEE) and 5 mg MPA were compared over 3 years to a similar group of women not taking hormone therapy (33). By the end of the third year, only 3 of 34 (8%) treated and 1 of 34 (3%) untreated women had any increase in fibroid volume over baseline (32). Postmenopausal women with known fibroids, followed with sonography, were noted to have an average 0.5 cm increase in the diameter of fibroid after using transdermal estrogen patches plus oral progesterone for 12 months (33). Women taking oral estrogen and progesterone had no increase in fibroid size (34).
Tissue Injury Cellular injury or inﬂammation resulting from an environmental agent, infection, or hypoxia was proposed as a mechanism for initiation of fibroid formation (43). Repetitive tissue injury to the endometrium and endothelium might promote the development of monoclonal smooth muscle proliferations in the muscular wall. Frequent mucosal injury with stromal repair (menstruation) may release growth factors that promote the high frequency of uterine fibroids (43).
No increased incidence was found in women with prior sexually transmitted infections, prior intrauterine device (IUD) use or prior talc exposure (35). Herpes simplex virus (HSV) I or II, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and chlamydia were not found in fibroids.