In this post, I link to and excerpt from StatPearls‘ Postmenopausal Bleeding [Full-Text HTML]. Last Update: September 18, 2022.
All that follows is from the above resource.
Introduction
The average age of menopause is fifty-one years. Menopause occurs when the ovaries cease making estrogen, and the patient is no longer ovulatory. The level of the follicle-stimulating hormone is elevated after menopause, as the hypothalamic-pituitary-ovarian axis attempts to stimulate ovulation despite the ovaries no longer being able. A woman is labeled menopausal if she has gone twelve months without menses.
After a woman is postmenopausal, further vaginal bleeding is no longer considered normal. The differential diagnosis of postmenopausal bleeding includes many benign and malignant conditions, the most common of which is atrophy, but the most concerning possible etiology is endometrial cancer. As with most malignancies, early diagnosis may lead to a better prognosis. Therefore, a postmenopausal woman with vaginal bleeding should be promptly and appropriately evaluated.
Etiology
Abnormal genital bleeding is often attributed to the uterus, with postmenopausal women describing bleeding as “having a period” again despite not having had menses for quite some time. Despite this natural inclination, bleeding can arise from the perineum, vulva, vagina, cervix, or fallopian tubes. Bleeding can be related to ovarian pathology. The etiology of bleeding may also be non-gynecologic. Bleeding from the urethra, bladder, or GI tract (anus, rectum, bowel) could be mistaken for vaginal bleeding.
The most common cause of postmenopausal bleeding is atrophy, either of the endometrium or the vaginal mucosa.[1] Other common etiologies are endometrial hyperplasia, endometrial polyps, and submucous leiomyomas. While these etiologies all lead to bleeding from a uterine source, they must be distinguished from non-gynecologic bleeding as above.
Epidemiology
Vaginal bleeding is reported in about 4-11% of postmenopausal women.[2][3][4][5] Postmenopausal bleeding accounts for approximately 5% of gynecologic office visits.[6] About 1-14% of postmenopausal bleeding will be secondary to endometrial cancer.[7]
Endometrial cancer is the most common gynecologic malignancy in the United States. In 2017, there were over 61,000 new cases of uterine cancer; there were almost 11,000 deaths.[7] Most cases of uterine cancer are endometrial in origin (92%).[7] Vaginal bleeding is the presenting sign in more than 90% of postmenopausal women with endometrial cancer.[7]
Pathophysiology
Lack of estrogen causes atrophy of the vagina and endometrium. Inside the uterus, the collapsed and atrophic surfaces of the endometrium contain scant or no fluid to prevent friction inside the cavity.[8] This leads to the development of micro-erosions of the epithelial surface, with subsequent chronic inflammation. This chronic endometritis is prone to spotting or light bleeding. A pelvic ultrasound would reveal a normal-appearing small postmenopausal uterus, small postmenopausal ovaries, and a thin endometrial stripe.
On the other hand, premalignant or malignant conditions of the endometrium often arise after unopposed estrogen. Systemic estrogen-only therapy, chronic anovulation (such as in polycystic ovarian syndrome), obesity, and estrogen-secreting tumors can lead to abnormal endometrial changes. Anovulation also leads to infrequent, insufficient shedding of the endometrium. Some women have genetic predispositions to endometrial cancer, including Lynch syndrome and Cowden disease.[9]
Histopathology
Normal proliferative endometrium contains glands that are regularly spaced and that lie within stroma at a gland: stroma ratio of 1 to 1. Atrophic endometrial cells, on the other hand, are smaller and more cuboidal than proliferative endometrium. Because atrophic postmenopausal endometrium is no longer active, there are few or no mitotic cells. The glands become cystic, appearing large and round. The stroma between glands is inactive.
Chronic endometritis can be secondary to atrophy or infection. It is diagnosed traditionally on histology by plasma cell infiltration. On hysteroscopy, one can also grossly see endometrial hyperemia, edema, or micro-polyps (measuring less than 1 mm).[10]
“Endometrial reactive changes” is terminology linked to a heterogeneous group of morphologies of the endometrium. These morphologies are associated with inciting events like infection, stromal breakdown, or recent instrumentation. They can also be seen with hormonal imbalance.
Endometrial hyperplasia demonstrates a widespread crowding of endometrial glands. Without atypia, gland cytology is normal, and only occasional mitotic figures are found. Suppose atypia is present, as, in endometrial intraepithelial neoplasia (EIN), both gland crowding and abnormal gland nuclei are seen. EIN is considered a cancer precursor.
Endometrial cancer can be type I or type II:[11][12]
Endometrioid Adenocarcinoma Type I: This is the most common of the histologic types (more than 75% of endometrial cancers). On histology, one may see solid areas, maze-like glands, or appreciable cribiforming. Most are low-grade and are confined to the uterus at diagnosis. EIN is the precursor lesion for this type of endometrial cancer.
Endometrioid Adenocarcinoma Type II: These are considered to be high grade and include clear cell, carcinosarcoma, and papillary serous histologies. These cancers have a higher risk of extrauterine disease, and they have a worse prognosis than type I tumors. For example, 10% of uterine cancers are papillary serous, but they are responsible for nearly 40% of deaths.
Evaluation
In addition to physical examination, evaluation of postmenopausal bleeding is directed at either diagnosing or excluding hyperplasia or malignancy. The American College of Obstetricians and Gynecologists recommend transvaginal ultrasound for initial evaluation.[7] The endometrial thickness is measured in an anterior-posterior fashion, at the area of endometrial echo of maximal thickness, on a long-axis view of the uterus.[7] An endometrial thickness of less than or equal to 4 mm has a negative predictive value greater than 99% for endometrial carcinoma. The ultrasound may also identify leiomyomas or pathology of the adnexa.
Findings on ultrasound for which endometrial sampling are indicated include:
Endometrial sampling should also be obtained in patients with persistent or recurrent bleeding, even in the setting of a thin endometrial echo.[7] It is reasonable, to begin with, endometrial sampling first rather than ultrasound, in patients with a higher pretest probability for malignancy.[7] The use of 4 mm endometrial thickness as a threshold may miss endometrial cancer for 1 in 339 patients.[7]
The diagnostic accuracy of endometrial sampling correlates positively with the amount of tissue that is collected.[16] There are several methods of endometrial sampling. Dilation and curettage has been used for years and has a sensitivity for endometrial cancer exceeding 90%.[17][18] Office endometrial biopsy can also be performed using metal curettes or flexible plastic samplers. Both of these have been determined to be adequate methods for endometrial sampling.[19][20][21]
It is common for endometrial sampling to result in findings that are insufficient for diagnosis, with rates of sampling failure up to 54%.[7] If sampling was performed first and was inadequate, a follow-up ultrasound may be performed. If a subsequent transvaginal ultrasound shows a thin endometrium, and if bleeding has stopped, no further evaluation is necessary.[7]
A thickened endometrial echo may be caused, not by hyperplasia or malignancy, but by intracavitary lesions such as endometrial polyps. If ultrasound findings are suggestive of such lesions, or if there is a history-indicated suspicion (for example, prior polyps), additional imaging may help to identify if a polyp or other intracavitary lesion is present. Saline-infusion ultrasonography or hysterosalpingogram may be useful in these cases.
Blind sampling may miss focal lesions or intrauterine pathology, such as polyps. Mass lesions may deflect flexible endometrial sampling devices. For patients with insufficient sampling, or with persistent vaginal bleeding in whom focal lesions may have been missed, additional evaluation should be considered. Hysteroscopy with dilation and curettage or directed biopsy may be warranted in these patients.[7][12]
Treatment / Management
The etiology dictates the management of postmenopausal bleeding.
Atrophy
Bleeding is usually self-limited and requires no treatment. Vulvar and vaginal atrophy may be treated with lubricants during intercourse, topical hormones (estrogen, DHEA), oral hormonal receptor modulator (ospemifene), etc.
Polyp
Removal of the polyp may resolve the bleeding. Endometrial polyps are often benign, but they can contain hyperplasia or malignancy approximately 5% of the time.[22] Because of this, complete hysteroscopic removal should be considered. Removal is recommended, especially in patients with symptoms or at risk of malignancy (larger polyps, tamoxifen use, obesity, diabetes).[23]
Submucous Leiomyoma
Fibroids may be removed using a hysteroscope or laparoscope or they may be ablated with various devices (some currently investigational). Some lesions are amenable to uterine artery embolization. Ultimately, if minimally-invasive approaches are unsuccessful and the patient is significantly bothered, definitive management with hysterectomy can be considered.
Cervicitis: Treatment of cervical infections is recommended, as indicated by the organism.
Cervical Cancer: Treatment is based on stage and may include surgery or radiation.
Endometritis: Administration of doxycycline can be considered. In addition to antibiotic effects, doxycycline may have anti-inflammatory effects.[24]
Endometrial Hyperplasia or Malignancy
Start here.
