Treatments of Uterine Leiomyomas

Like the medical treatment of uterine leiomyomas, danazol, gestrinone, mifepristone, and GnRH-a, with or without add-back therapy, have been proposed for the treatment of endometriosis as well (Olive et al. 2001 Stones et al. 2004), but unlike leiomyomas, oral contraceptive pills, in cyclic or continuous administration, and medroxyprogesterone acetate also seem to be effective (Olive et al. 2001 Stones et al. 2004). A significant benefit in terms of pelvic pain relief also is obtained with the use of nonsteroidal anti-inflammatory drugs (Olive et al. 2001 Stones et al. 2004). 

Palomba S, Affinito P, Di Carlo C, Bifulco G, Nappi C (1999) Longterm administration of tibolone plus gonadotropin-releasing hormone agonist for treatment of uterine leiomyomas effectiveness and effects on vasomotor symptoms, bone mass, and lipid profile. Fertil Steril 72 889-895... 

Brunereau L, Herbreteau D, Gallas S, Cottier JP, Lebrun JL, Tranquart F, Fauchier F, Body G, Rouleau P (2000) Uterine artery embolization in the primary treatment of uterine leiomyomas technical features and prospective follow-up with clinical and sonographic examinations in 58 patients. AJR Am J Roentgenol 175 1267-1272... 

To date, the standard treatment for uterine leiomyomas is their laparo-tomic/laparoscopic excision in women who want to preserve their fertility, whereas the use of a more extensive surgery, such as the hysterectomy, is reserved for disseminating uterine leiomyomatosis, generally in the peri-menopausal period (Stewart 2001 Palomba et al. 2006a). 

Minakuchi K, Kawamura N, Tsujimura A (1999) Remarkable and persistent shrinkage of uterine leiomyoma associated with interferon alfa treatment for hepatitis. Lancet 353 2127-2128... 

Palomba S, Sammartino A, Di Carlo C, Affinito P, Zullo F, Nappi C (2001) Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril 76 38-43... 

Uterine leiomyomas, or fibroids, are the most common type of solid tumors in adult women, clinically apparent in at least 25% of those of reproductive age [24-26]. Abnormal menstrual bleeding, pelvic pain, and infertility are the most commonly experienced symptoms in these women. Uterine fibroids are the leading cause of hysterectomies performed in the United States, accounting for over 200,000 of these procedures each year. Other invasive surgical interventions for the treatment of uterine fibroids include myomectomy and uterine artery embolization. Leiomyomas are estrogen-responsive tumors that can be treated... 

The most common benign gynecological diseases, for prevalence and related economic costs, are probably uterine leiomyomas and endometriosis (Stewart 2001 Missmer et al. 2003). Notwithstanding the fact that both conditions are characterized by a sex-hormone-related development and by the possibility of a medical treatment consisting of hormonal manipulation, at present the main approach to these conditions is surgical excision (Palomba et al. 2006a Olive etal. 2001). 

First we shall describe the effects of tamoxifen, a first-generation SERM used as adjuvant treatment in women with breast cancer, on uterine leiomyomas and endometriosis. Considerable space will be devoted to raloxifene, a second-generation SERM administered for the prevention and treatment of postmenopausal women recently tested for the treatment of these two sex-hormone-related diseases. Unfortunately, at present no or very little data are available on the new third-generation SERMs such as lasofoxifene, idroxifene, droloxifene, ospemifene, azomifene, fulvestrant, and MDL 103.323. 

Uterine leiomyomas are the most frequent benign disease of the female reproductive apparatus. At least 20-25% of women of fertile age and 50% of women studied in postmortem have uterine leiomyomas (Stewart 2001 Palomba et al. 2005a). In between 20 and 50% of cases, the uterine leiomyomas cause a clinically relevant symptomatology (such as menorrhagia, infertility, recurrent abortion, pelvic pain, and so on) and treatment is required (Stewart 2001 Palomba et al. 2006a). Thus, this disease is one of the main causes of health expense in the field of gynecology (Stewart 2001 Palomba et al. 2006a). In fact,... 

The effects of tamoxifen on uterine leiomyomas have been studied also in postmenopausal patients with breast cancer (Schwartz et al. 1998). After an average treatment of about 1 year, uterine and leiomyoma volumes increased significantly, confirming an agonistic effect of tamoxifen on the uterus. No significant difference in agonist effect on the uterus has been detected between tamoxifen and toremifene (Tomas et al. 1995). 

At present, the only SERMs routinely used in clinical practice are tamoxifen and raloxifene. Tamoxifen is used essentially as adjuvant treatment in women with breast cancer. Its use is related to estrogenic effects on the uterus. Specifically, tamoxifen can be associated with an increase not only in endometrial hyperplasia and cancer risk but also in uterine leiomyoma dimensions and in a risk of developing active endometriotic lesions. 

Raloxifene is actually used for the treatment and prevention of postmenopausal osteoporosis. Also, if raloxifene has been shown to have any effect on uterine leiomyomas in vitro and in animal models, to date no concrete efficacy has been demonstrated in normally cycled premenopausal women. Moreover, the addition of raloxifene to GnRH-a administration can be useful for limiting GnRH-a-related side effects and increasing the rate of reduction in tumor size. 

Shozu M, Murakami K, Segawa T, Kasai T, Inoue M (2003) Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor. Fertil Steril 79 628-631... 

Razavi MK, Hwang G et al (2003) Abdominal myomectomy versus uterine fibroid embolization in the treatment of symptomatic uterine leiomyomas. AJR Am J Roentgenol 180 1571-1575... 

Brunereau L, Herbreteau D, Gallas S et al. (2000) Uterine artery embolization as the primary treatment of leiomyomas. Am J Roentgenol 175 1267-1272... 

Marret H, Tranquart F, Sauget S, Alonso AM, Cottier JP, Herbreteau D (2004a) Contrast-enhanced sonography during uterine artery embolization for the treatment of leiomyomas. Ultrasound Obstet Gynecol 23 77-79... 

Fig. 12.1. Variation (%) from baseline in uterine and leiomyoma sizes and in A size after 3, 6, 9, and 12 cycles of treatment. Values are reported as mean SD.a p < 0.05 vs. baseline. A = group A = group B (Palomba et al. 2001). Permission to publish from Elsevier...

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