Medical Treatment of Uterine Fibroids
Medical Treatment of Uterine Fibroids
Parsanezhad ME, Azmoon M, Alborzi S, et al
Fertil Steril. 2010;93:192-198
Uterine fibroids are benign tumors originating from the smooth muscle of the myometrium of the uterus. They are the most common tumor affecting the reproductive organs and are found in up to 25% of women. Fibroids may be symptomatic or asymptomatic. The severity of symptoms typically depends on size, number of myomas, and tumor location. Fibroids that grow towards the cavity (submucous fibroid) generally lead to an abnormal bleeding pattern. Intramural and subserous tumors are more likely to cause problems (pressure, difficulty urinating, dyspareunia, dysmenorrhea) as a result of their size. Location (of submucous myomas) and size (of intramural and subserous myomas) may also contribute to decreased fecundity.
Fibroids should be treated when they produce symptoms or if they grow rapidly and malignant transformation is suspected. If malignancy is suspected, treatment must be surgical. In other cases, several treatment options are available. Gonadotropin-releasing hormone (GnRH) agonists, selective estrogen-receptor modulators, progesterone antagonists, and androgens are medical options; other choices include uterine artery embolization and surgery. Surgery may be conservative (myomectomy, hysteroscopic resection) or definitive (hysterectomy). Because fibroids are hormone sensitive and grow in an estrogenic environment, medical therapies that modify this environment may be successfully used in their management.
This randomized controlled trial compared the effect of an aromatase inhibitor (letrozole, 2.5 mg) with "standard" GnRH agonist therapy (triptorelin, 3.75 mg, given monthly by intramuscular injection). Women 18-42 years of age with a single, symptomatic myoma larger than 5 cm were randomly assigned to receive either letrozole or triptorelin for 12 weeks. Assessments were done at baseline and at weeks 2, 4, 6, 8, and 12, and changes in fibroid size and hormone levels were compared. Baseline characteristics of the 2 groups of women were similar.
At the end of 3 months, the volume of myoma was reduced by 45.6% in the letrozole group and 33.2% in the triptorelin group. The change in size was similar in the 2 groups and differed significantly from baseline in both groups. No women in the letrozole group reported hot flashes, whereas almost all women receiving triptorelin experienced hot flashes of some degree. Hormone levels remained unchanged over the 12 weeks in the letrozole group. In the triptorelin group, an initial flare effect was seen -- at week 2, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were elevated -- with subsequent significant suppression of all hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, and testosterone). The investigators concluded that aromatase inhibitors can be used successfully to manage symptomatic fibroids without vasomotor symptoms and significant changes in hormone levels.
Medical management of myomas may be needed. Typically, good candidates for medical treatment are women with anemia preoperatively, perimenopausal women who are about to enter menopause, and women with large fibroids in whom size reduction before surgery is desired. Medical therapy may also be considered in women who wish to retain their uterus for reproductive purposes, although fibroids typically regrow on cessation of medical treatment.
Fibroids tend to grow in an estrogenic environment. They contain receptors for both estrogen and progesterone. In addition, fibroids have clinically significant aromatase activity and produce estrogen locally from circulating androgens. Medical therapy that lowers estrogen levels (such as a GnRH agonist), interferes with progesterone (mifepristone), modifies estrogen response (raloxifene), or reduces aromatase activity (letrozole) may be effective. All of these therapies lead to a significant but temporary reduction in size of the fibroid and improve symptoms in most cases. Medical intervention may prepare the patient for surgery and in some cases render surgery unnecessary if, in the interim, the patient enters menopause. For reproductive purposes, the effect of medical therapy is less obvious because on discontinuation of therapy, myomas tend to regrow.
This study found that aromatase inhibitors are as effective as a GnRH agonist with fewer side effects. However, body mass index was not compared between the 2 groups, so it is unclear whether it influences the effectiveness of the drug. Long-term follow-up is also needed to see how soon fibroids regain their preintervention size after discontinuation of medical therapy. Finally, whether aromatase inhibitors could be used for a longer period, because they are not accompanied by vasomotor symptoms or hypoestrogenism, must also be determined.
On the basis of this report, letrozole may be another tool in the management of symptomatic fibroids. A lack of information on subsequent reproductive outcome currently restricts the use of letrozole to women without infertility.
Abstract
A Randomized, Controlled Clinical Trial Comparing the Effects of Aromatase Inhibitor (Letrozole) and Gonadotropin-Releasing Hormone Agonist (Triptorelin) on Uterine Leiomyoma Volume and Hormonal Status
Parsanezhad ME, Azmoon M, Alborzi S, et al
Fertil Steril. 2010;93:192-198
Background
Uterine fibroids are benign tumors originating from the smooth muscle of the myometrium of the uterus. They are the most common tumor affecting the reproductive organs and are found in up to 25% of women. Fibroids may be symptomatic or asymptomatic. The severity of symptoms typically depends on size, number of myomas, and tumor location. Fibroids that grow towards the cavity (submucous fibroid) generally lead to an abnormal bleeding pattern. Intramural and subserous tumors are more likely to cause problems (pressure, difficulty urinating, dyspareunia, dysmenorrhea) as a result of their size. Location (of submucous myomas) and size (of intramural and subserous myomas) may also contribute to decreased fecundity.
Fibroids should be treated when they produce symptoms or if they grow rapidly and malignant transformation is suspected. If malignancy is suspected, treatment must be surgical. In other cases, several treatment options are available. Gonadotropin-releasing hormone (GnRH) agonists, selective estrogen-receptor modulators, progesterone antagonists, and androgens are medical options; other choices include uterine artery embolization and surgery. Surgery may be conservative (myomectomy, hysteroscopic resection) or definitive (hysterectomy). Because fibroids are hormone sensitive and grow in an estrogenic environment, medical therapies that modify this environment may be successfully used in their management.
Study Summary
This randomized controlled trial compared the effect of an aromatase inhibitor (letrozole, 2.5 mg) with "standard" GnRH agonist therapy (triptorelin, 3.75 mg, given monthly by intramuscular injection). Women 18-42 years of age with a single, symptomatic myoma larger than 5 cm were randomly assigned to receive either letrozole or triptorelin for 12 weeks. Assessments were done at baseline and at weeks 2, 4, 6, 8, and 12, and changes in fibroid size and hormone levels were compared. Baseline characteristics of the 2 groups of women were similar.
At the end of 3 months, the volume of myoma was reduced by 45.6% in the letrozole group and 33.2% in the triptorelin group. The change in size was similar in the 2 groups and differed significantly from baseline in both groups. No women in the letrozole group reported hot flashes, whereas almost all women receiving triptorelin experienced hot flashes of some degree. Hormone levels remained unchanged over the 12 weeks in the letrozole group. In the triptorelin group, an initial flare effect was seen -- at week 2, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were elevated -- with subsequent significant suppression of all hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, and testosterone). The investigators concluded that aromatase inhibitors can be used successfully to manage symptomatic fibroids without vasomotor symptoms and significant changes in hormone levels.
Viewpoint
Medical management of myomas may be needed. Typically, good candidates for medical treatment are women with anemia preoperatively, perimenopausal women who are about to enter menopause, and women with large fibroids in whom size reduction before surgery is desired. Medical therapy may also be considered in women who wish to retain their uterus for reproductive purposes, although fibroids typically regrow on cessation of medical treatment.
Fibroids tend to grow in an estrogenic environment. They contain receptors for both estrogen and progesterone. In addition, fibroids have clinically significant aromatase activity and produce estrogen locally from circulating androgens. Medical therapy that lowers estrogen levels (such as a GnRH agonist), interferes with progesterone (mifepristone), modifies estrogen response (raloxifene), or reduces aromatase activity (letrozole) may be effective. All of these therapies lead to a significant but temporary reduction in size of the fibroid and improve symptoms in most cases. Medical intervention may prepare the patient for surgery and in some cases render surgery unnecessary if, in the interim, the patient enters menopause. For reproductive purposes, the effect of medical therapy is less obvious because on discontinuation of therapy, myomas tend to regrow.
This study found that aromatase inhibitors are as effective as a GnRH agonist with fewer side effects. However, body mass index was not compared between the 2 groups, so it is unclear whether it influences the effectiveness of the drug. Long-term follow-up is also needed to see how soon fibroids regain their preintervention size after discontinuation of medical therapy. Finally, whether aromatase inhibitors could be used for a longer period, because they are not accompanied by vasomotor symptoms or hypoestrogenism, must also be determined.
On the basis of this report, letrozole may be another tool in the management of symptomatic fibroids. A lack of information on subsequent reproductive outcome currently restricts the use of letrozole to women without infertility.
Abstract
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