Endometrial hyperplasia medical therapy: Difference between revisions
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Options for the management of EH include surveillance, progestin therapy, or hysterectomy. | |||
Other treatment approaches include pharmacologic treatments other than progestins or conservative surgical treatment. These modalities are not used commonly and have not been well studied. (See 'Other treatments' below.) | |||
All management strategies should also be accompanied by removal of the extrinsic or intrinsic source of unopposed estrogen, since excess exposure to estrogen is the main etiology of endometrial neoplasia. | |||
This may be identifying and stopping use of nonprescription medications or topical products that contain estrogen, stopping unopposed estrogen therapy, correcting ovulatory dysfunction (eg, due to polycystic ovarian syndrome or hyperprolactinemia) (table 1), losing weight, or, rarely, removing an estrogen-producing neoplasm. (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women", section on 'Irregular bleeding (ovulatory dysfunction)'.) | |||
Weight loss in obese women has multiple health benefits in addition to reducing high levels of endogenous estrogens due to estradiol and estrone production by adipocytes. Bariatric surgery may be of benefit in reducing this risk [4]. (See "Overweight and obesity in adults: Health consequences".) | |||
For women with ovulatory dysfunction, the etiology should be treated (eg, prolactinoma), or if the ovulatory dysfunction is likely to be chronic (eg, polycystic ovarian syndrome), women may need maintenance progestin therapy after EH regression. | |||
Surveillance — Surveillance alone may be utilized if the risk of an occult cancer or progression to cancer is low and the inciting factor that resulted in endometrial proliferation has been eliminated (eg, patient with anovulation, now corrected, who had developed simple hyperplasia without atypia). | |||
Progestin therapy — There are no US Food and Drug Administration (FDA)-approved therapies for the treatment of EH, although various progestins are approved for EH prevention, and megestrol acetate and depot medroxyprogesterone acetate are approved for treatment of endometrial carcinoma. Progestins are the most commonly used therapy, since they oppose the effect of estrogen on the endometrium. When appropriate and successful, progestin therapy allows for future attempts at pregnancy. | |||
Hysterectomy — Total hysterectomy is definitive treatment, but is a major surgical procedure and precludes future fertility. Hysterectomy is usually reserved for postmenopausal women, women who do not desire future fertility, or those with pathology suggesting high risk of concomitant endometrial carcinoma. | |||
Other treatments — Treatment with nonprogestin medications or conservative surgery is not standard clinical practice, but has been described [5,6]. | |||
●Nonprogestin medications | |||
•Gonadotropin-releasing hormone (GnRH) agonists were used in combination with a levonorgestrel-releasing intrauterine device with a release rate of 19.5 mcg/day for five years (Mirena; LNg52/5) to successfully treat 24 premenopausal women with either atypical EH or early-stage endometrial carcinoma [7]. | |||
•Aromatase inhibitors have been administered to block endogenous estrogen production in patients with EH. Anastrozole was used successfully to treat 11 obese postmenopausal women with atypical (n = 2) and nonatypical EH (n = 9) [8]. A small prospective study of 45 patients showed no simple EH following treatment [9]. | |||
•Ovulation induction (eg, with clomiphene or aromatase inhibitors) in reproductive-age women will result in formation of a corpus luteum, exposure to endogenous progesterone, and resolution of EH in some women [10]. Pregnancy is highly unlikely in the setting of ongoing EH. Careful surveillance is needed to assure EH regression. This approach is favored for women with EH without atypia who desire pregnancy. | |||
•Metformin has been shown to both have antiproliferative effects and to reduce insulin resistance, which may play a role in the development of endometrial carcinoma in overweight and obese females [11]. A small prospective study of 16 patients showed improved resolution of atypical EH when metformin was added to megestrol acetate. Patients with metabolic syndrome may find particular benefit [12]. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)".) | |||
•Danazol has been used to successfully treat EH, but is seldom used due to significant side effects when taken orally [13-15]. In a series of postmenopausal women, danazol (400 mg per day for six months) caused complete regression in 83 percent of patients, with 8 percent with a relapse within four months of discontinuing therapy [13]. | |||
●Alternative surgical treatments | |||
•Hysteroscopic resection of EH was reported to be effective in 68 of 73 treated women, but the long-term consequence of this treatment remains to be determined [16]. | |||
•Bariatric surgery may show promise. There was a significant decreased rate of all cancers following bariatric surgery compared to obese controls (3.5 versus 5.8 percent) in a large retrospective study [4]. The most frequent cancer in the group who had bariatric surgery was breast (28.3 percent), followed by endometrial (17 percent). In the obese control group, the most common cancer was endometrial (62.3 percent). | |||
==References== | ==References== | ||
Revision as of 09:15, 19 February 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Soujanya Thummathati, MBBS [2]
Overview
Progesterone is the preferred drug for the treatment of benign hyperplasia. The management of endometrial hyperplasia depends upon the desire for future childbearing.[1][2]
Medical Therapy
- Patients with endometrial hyperplasia without atypia are treated conservatively through normalization of the menstrual cycles, whereas patients with atypical hyperplasia or endometrioid intraepithelial neoplasia are treated surgically.[1][2]
Treatment of endometrial hyperplasia | |||||||||||||||||||||||||||||||||||||||||||||
Hyperplasia without atypia
| Hyperplasia with atypia | ||||||||||||||||||||||||||||||||||||||||||||
Conservative
| Desire for pregnancy? | ||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||
Conservative
| |||||||||||||||||||||||||||||||||||||||||||||
Progestins (cyclic/continuous) | |||||||||||||||||||||||||||||||||||||||||||||
Options for the management of EH include surveillance, progestin therapy, or hysterectomy.
Other treatment approaches include pharmacologic treatments other than progestins or conservative surgical treatment. These modalities are not used commonly and have not been well studied. (See 'Other treatments' below.)
All management strategies should also be accompanied by removal of the extrinsic or intrinsic source of unopposed estrogen, since excess exposure to estrogen is the main etiology of endometrial neoplasia.
This may be identifying and stopping use of nonprescription medications or topical products that contain estrogen, stopping unopposed estrogen therapy, correcting ovulatory dysfunction (eg, due to polycystic ovarian syndrome or hyperprolactinemia) (table 1), losing weight, or, rarely, removing an estrogen-producing neoplasm. (See "Approach to abnormal uterine bleeding in nonpregnant reproductive-age women", section on 'Irregular bleeding (ovulatory dysfunction)'.)
Weight loss in obese women has multiple health benefits in addition to reducing high levels of endogenous estrogens due to estradiol and estrone production by adipocytes. Bariatric surgery may be of benefit in reducing this risk [4]. (See "Overweight and obesity in adults: Health consequences".)
For women with ovulatory dysfunction, the etiology should be treated (eg, prolactinoma), or if the ovulatory dysfunction is likely to be chronic (eg, polycystic ovarian syndrome), women may need maintenance progestin therapy after EH regression.
Surveillance — Surveillance alone may be utilized if the risk of an occult cancer or progression to cancer is low and the inciting factor that resulted in endometrial proliferation has been eliminated (eg, patient with anovulation, now corrected, who had developed simple hyperplasia without atypia).
Progestin therapy — There are no US Food and Drug Administration (FDA)-approved therapies for the treatment of EH, although various progestins are approved for EH prevention, and megestrol acetate and depot medroxyprogesterone acetate are approved for treatment of endometrial carcinoma. Progestins are the most commonly used therapy, since they oppose the effect of estrogen on the endometrium. When appropriate and successful, progestin therapy allows for future attempts at pregnancy.
Hysterectomy — Total hysterectomy is definitive treatment, but is a major surgical procedure and precludes future fertility. Hysterectomy is usually reserved for postmenopausal women, women who do not desire future fertility, or those with pathology suggesting high risk of concomitant endometrial carcinoma.
Other treatments — Treatment with nonprogestin medications or conservative surgery is not standard clinical practice, but has been described [5,6].
●Nonprogestin medications
•Gonadotropin-releasing hormone (GnRH) agonists were used in combination with a levonorgestrel-releasing intrauterine device with a release rate of 19.5 mcg/day for five years (Mirena; LNg52/5) to successfully treat 24 premenopausal women with either atypical EH or early-stage endometrial carcinoma [7].
•Aromatase inhibitors have been administered to block endogenous estrogen production in patients with EH. Anastrozole was used successfully to treat 11 obese postmenopausal women with atypical (n = 2) and nonatypical EH (n = 9) [8]. A small prospective study of 45 patients showed no simple EH following treatment [9].
•Ovulation induction (eg, with clomiphene or aromatase inhibitors) in reproductive-age women will result in formation of a corpus luteum, exposure to endogenous progesterone, and resolution of EH in some women [10]. Pregnancy is highly unlikely in the setting of ongoing EH. Careful surveillance is needed to assure EH regression. This approach is favored for women with EH without atypia who desire pregnancy.
•Metformin has been shown to both have antiproliferative effects and to reduce insulin resistance, which may play a role in the development of endometrial carcinoma in overweight and obese females [11]. A small prospective study of 16 patients showed improved resolution of atypical EH when metformin was added to megestrol acetate. Patients with metabolic syndrome may find particular benefit [12]. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)".)
•Danazol has been used to successfully treat EH, but is seldom used due to significant side effects when taken orally [13-15]. In a series of postmenopausal women, danazol (400 mg per day for six months) caused complete regression in 83 percent of patients, with 8 percent with a relapse within four months of discontinuing therapy [13].
●Alternative surgical treatments
•Hysteroscopic resection of EH was reported to be effective in 68 of 73 treated women, but the long-term consequence of this treatment remains to be determined [16].
•Bariatric surgery may show promise. There was a significant decreased rate of all cancers following bariatric surgery compared to obese controls (3.5 versus 5.8 percent) in a large retrospective study [4]. The most frequent cancer in the group who had bariatric surgery was breast (28.3 percent), followed by endometrial (17 percent). In the obese control group, the most common cancer was endometrial (62.3 percent).
References
- ↑ 1.0 1.1 Emons G, Beckmann MW, Schmidt D, Mallmann P, Uterus commission of the Gynecological Oncology Working Group (AGO) (2015). "New WHO Classification of Endometrial Hyperplasias". Geburtshilfe Frauenheilkd. 75 (2): 135–136. doi:10.1055/s-0034-1396256. PMC 4361167. PMID 25797956.
- ↑ 2.0 2.1 Baak JP, Mutter GL (2005). "EIN and WHO94". J Clin Pathol. 58 (1): 1–6. doi:10.1136/jcp.2004.021071. PMC 1770545. PMID 15623473.