Benign Endometrial Diseases

Dr.S.Davoodi

• Normal cycle is divided into two phases: follicular

and luteal.

• The follicular phase begins with the onset of

menses and ends on the day before the luteinizing

hormone (LH) surge.{ 14 to 21 days }

• The luteal phase begins on the day of the LH surge

and ends at the onset of the next menses. { 14

days }

• Benign endometrial histology includes atrophy

(absence of a hormonal effect), proliferative

endometrium (estrogen effect), secretory

endometrium (progestin effect), disordered or dys

synchronous endometrium (implies irregular

shedding of the endometrium secondary to

unopposed estrogen), and endometritis

Proliferative endometrium

• During this phase, the proliferative

endometrium undergoes cell

multiplication and tissue growth

• This phase is variable in length.

During this phase, the tubular

glands, which have columnar cells,

and dense stroma proliferate and

thicken, following the shedding off

phase from a previous menstruation.

Secretory endometrium

• The secretory endometrium is a

stage of the menstrual cycle in which

a nearly mature endometrium has a

layer of grandular epithelium with

round nuclei, thickened endometrium

and curled uterine glands with

collections of glycogen within them.

This stage typically happens two days

after ovulation

• During the normal menstrual cycle, proliferative

endometrium is found during the follicular phase, and

secretory endometrium is found during the luteal phase.

Normal proliferative endometrium exhibits no crowding of

glands within the stroma (<50 percent ratio of glands to

stroma).

• Normal secretory endometrium may have >50 percent

gland to stroma ratio.

Disordered Proliferative Endometrium

• At the time of perimenopause, hormone levels fluctuate.

Because of the irregularity of hormone production, endometrial

growth becomes irregular, leading to irregular cycles. This is

what some people call disordered proliferative endometrium,

which simply implies that the growth of the lining of the uterus is

not regular( high levels of estrogen from low progesterone

levels)

• Another potential cause of disordered changes in the

proliferative endometrium is the use of birth control pills

• If not corrected, this condition may progress to abnormal

thickening of the endometrium (endometrial hyperplasia)

Treatment

The most common treatment for endometrial hyperplasia,

which occurs when there is proliferation of the

endometrium, is progestin therapy

Endometrial Hyperplasia

Endometrial hyperplasia is characterized by a

proliferation of endometrial glands of irregular

size and shape. Compared with proliferative

endometrium, there is an increase in the

endometrial gland to stroma ratio. Endometrial

hyperplasia virtually always results from chronic

estrogen stimulation unopposed by the counter

balancing effects of progesterone

• The WHO classification of endometria hyperplasia

• is based upon two features:

• The glandular/stromal architectural pattern of the endometrium,

which is described as either simple or complex

• The presence or absence of nuclear atypia

• This results in four possible categories of endometrial

hyperplasia:

• ●Simple hyperplasia without atypia

• ●Complex hyperplasia without atypia

• ●Simple atypical hyperplasia

• ●Complex atypical hyperplasia

• Simple versus complex hyperplasia:

• are characterized by the following features:

• Simple hyperplasia consists of glands that are mildly crowded.

They are frequently cystically dilated with only occasional

outpouching

• Mitoses may or

• may not be present

• in the glandular cells

• Complex hyperplasia consists of glands that are crowded (>50

percent gland to stromal ratio)

• The glands appear disorganized and have luminal outpouching.

Mitoses are typically present

RISK FACTORS

• The risk factors for endometrial hyperplasia are the same as

those for endometrial carcinoma

CLINICAL PRESENTATION

• Endometrial hyperplasia typically presents with

abnormal uterine bleeding and is most common in

women who are postmenopausal, and with

increasing age in premenopausal women.

Occasionally, women with no abnormal uterine

bleeding present with abnormal findings on cervical

cytology.

DIAGNOSTIC EVALUATION

Women with a clinical presentation suspicious for

endometrial hyperplasia are evaluated initially with

physical examination.

Pelvic sonography may also be performed to

evaluate for other etiologies of abnormal uterine

bleeding or to assess endometrial thickness in

postmenopausal women.

DIAGNOSIS

• Endometrial hyperplasia is a histologic

diagnosis made based upon the results of

evaluation of an endometrial biopsy, curettage

sample, or hysterectomy specimen.

FURTHER EVALUATION AFTER ENDOMETRIAL SAMPLING

• Negative endometrial sampling

• Insufficient cells on endometrial biopsy :

• Women with an endometrial biopsy result that has insufficient

endometrial cells should have sampling repeated with an office

biopsy or dilation and curettage (D&C).

• If two office endometrial biopsies have been unsuccessful, a

D&C should be performed.

• Cervical stenosis, a common cause of an unsuccessful biopsy,

can be managed with preprocedure cervical preparation or

dilation.

Evaluation of the endometrium

• The Pipelle device was more sensitive for the detection of

endometrial cancer and atypical hyperplasia than all other

sampling devices.

• Hystroscopy

• its use should be reserved for women at low risk of endometrial

cancer, and in whom the value of hysteroscopic resection of a

lesion is clear

• Transvaginal ultrasound

• In women with postmenopausal bleeding and not on hormonal

replacement therapy, an endometrial thickness of less than or

equal to 4 or 5 mm is associated with a low risk of endometrial

disease

• Persistent bleeding is worrisome even when the

• endometrial thickness is <4 mm, particularly if there are other

risk factors for endometrial cancer .

• Endometrial cancer can still occur in this setting since serous

carcinoma of the endometrium may arise from atrophic

endometrium. Therefore, further diagnostic evaluation is

indicated.

• Asymptomatic women with endometrial thickening or fluid

• we suggest sampling the endometrium of postmenopausal

women without uterine bleeding who have an endometrial

thickness >11 mm

• If curettage D&C is performed as a follow-up to

• endometrial biopsy, if the results are atypical endometrial

hyperplasia or carcinoma, the patient is managed as

appropriate.

• If the results are less severe or negative, the patient should be

managed based upon the results of the initial sample.

• Persistent or recurrent bleeding — If bleeding persists or recurs

after endometrial sampling with benign findings, further

evaluation is required.

• reevaluate such cases after three to six months.

• Premenopausal women

• TVUS should be performed on day 4, 5, or 6 of the

bleeding cycle, when the endometrium is expected to be

its thinnest (in reproductive-age women, normal

endometrial thickness in the proliferative phase is 4 to 8

mm and in the secretory phase 8 to 14 mm

• In asymptomatic premenopausal women, endometrial thickness

alone is not an indication for biopsy.

• Endometrial evaluation should be based on a combination of

factors , including cervical cytology results showing glandular

abnormalities or endometrial cells, a chronic history of estrogen

excess or anovulation (polycystic ovary syndrome),

• Women on tamoxifen

• women should have an endometrial biopsy if any abnormal

bleeding occurs

MANAGEMENT

• The choice of treatment of endometrial hyperplasia is based primarily

upon two factors: 1) nuclear atypia, and 2) the desire for fertility.

• The presence or absence of nuclear atypia is the primary factor in

determining whether treatment is needed.

• Options for the management of endometrial hyperplasia include:

• ●Hysterectomy.

• ●Hormonal management – Progestins are the usual therapy, since

they oppose the effect of estrogen on the endometrium. In a minority

of cases, treatment includes removal of the intrinsic or extrinsic

source of unopposed estrogen (eg, an estrogen-producing neoplasm).

• ●Surveillance with serial endometrial sampling.

• HYPERPLASIA WITHOUT ATYPIA

• The risk of progression to endometrial cancer is low for hyperplasia without atypia (<1 to 3 percent)

• . The goal of treatment is to prevent progression to cancer in a small number of women and to control abnormal uterine bleeding.

• Medroxyprogesterone acetate (MPA) has typically been first-line therapy for non-atypical endometrial hyperplasia. However, other options include estrogen-progestin contraceptives or the levonorgestrel-releasing intrauterine device, 20 mcg/day (LNg20; Mirena).

• The LNg20 appears to be more effective than oral progestins

for the treatment of non-atypical endometrial hyperplasia.

• For women treated with MPA, we prescribe 10 mg daily for

three to six months. Most women find this continuous dosing

schedule more acceptable than a cyclic regimen because

they do not have cyclic vaginal bleeding during treatment.

• A cyclic regimen of MPA (eg, 10 mg daily for 12 to 14 days each

month) may also be used.

• Micronized progesterone (100 to 200 mg) in a vaginal cream – In

one study, use of this agent from the 10th to the 25th day of the

menstrual cycle for three to six months resulted in regression of

endometrial hyperplasia without atypia to normal endometrium

• If regression to normal endometrium does not occur after three

to six months, the progestin dose may be increased, or a

combination of a systemic progestin and the LNg20 may be

used.

• ATYPICAL HYPERPLASIA

• Hysterectomy is the treatment of choice for women with

endometrial hyperplasia with atypia who are not planning future

pregnancy.

• Progestin therapy is an option for women who wish to preserve

fertility or who cannot tolerate surgery.

• The recommendation for hysterectomy is based upon the high

risk endometrial cancer in women with atypical endometrial

hyperplasia. Many women with atypical endometrial hyperplasia

diagnosed with endometrial sampling are found to have

concurrent foci of endometrial cancer

• Supracervical hysterectomy is not a valid option for

• these patients, since the potential for local extension of

the endometrial neoplasia into the cervix outweighs any

purported benefits of this surgical approach.

• Postmenopausal women

• For postmenopausal women with atypical endometrial

hyperplasia, we suggest hysterectomy with concomitant

bilateral salpingo-oophorectomy (BSO) rather than

hysterectomy alone

• Women with atypical endometrial hyperplasia who desire

future childbearing or are not appropriate for surgery may

be treated with progestin therapy. These women must be

able to comply with medical therapy and follow-up

endometrial sampling.

• Megestrol acetate is typically the oral progestin used for

atypical hyperplasia

• We often treat patients in this population with oral

megestrol acetate 80 mg twice per day .

• This may be increased to 160 mg twice per day

• if there is no regression of the hyperplasia on

• follow-up endometrial sampling.

• Alternatively, a 20 mcg/day levonorgestrel-releasing intrauterine device

(LNg20; Mirena)

• Other options for progestin therapy have been described and include

• ●MPA (oral) 10 to 20 mg daily

• ●Depot medroxyprogesterone (intramuscular) 150 mg every three months

• ●Micronized progesterone (vaginal) 100 to 200 mg daily

• For patients on maintenance progestin therapy, we repeat an endometrial

biopsy every 6 to 12 months initially.

• Danazol

• Gonadotropin-releasing hormone (GnRH) agonists or

antagonists may be given to produce a

pseudomenopausal state

• Aromatase inhibitors

Endometrial polyp

• Endometrial polyps are one of the most common

etiologies of abnormal genital bleeding in both

premenopausal and postmenopausal women .

• They are hyperplastic overgrowths of endometrial

glands and stroma that form a projection from the

surface of the endometrium (lining of the uterus).

They may also be asymptomatic. The great majority

of endometrial polyps are benign, but malignancy

occurs in some women

• Polyps can develop anywhere in the uterine cavity.

• Most risk factors for endometrial polyps involve increased levels or

activity of endogenous or exogenous estrogen.

• Tamoxifen :Polyps in these women may be large (>2 cm), multiple,

or show molecular alterations

• Obesity:those with a BMI ≥30 had a significantly higher rate of

polyps than other women

• Hereditary nonpolyposis colorectal cancer

• CLINICAL PRESENTATION

• Abnormal uterine bleeding

• Intermenstrual bleeding is the most frequent symptom in

premenopausal women with endometrial polyps

• Postmenopausal bleeding is another common presentation

• Incidental finding on imaging or hysteroscopy

• Endometrial cells on cervical cytology

• Prolapsed polyp

• DIAGNOSTIC EVALUATION

• Pelvic ultrasound and hysteroscopy

• sonohysterography

• CLINICAL COURSE

• Continued growth or regression

• Risk of malignancy — Approximately 95 percent of endometrial polyps are benign .

• malignant or hyperplastic was significantly higher in postmenopausal compared with premenopausal women and those with bleeding compared to those without bleeding

• polyps greater than 1.5 cm in diameter

• Tamoxifen

• CHOOSING A MANAGEMENT APPROACH

• Symptomatic endometrial polyps should be removed in all

women

• For other asymptomatic women, we perform polypectomy if the

following characteristics are present:

• ●Polyp >1.5 cm in diameter

• ●Multiple polyps

• ●Polyp prolapsed through the cervix

• ●Infertility

• Postmenopausal women — For postmenopausal women, we

recommend removal of all endometrial polyps

• Thank you