POSTMENOPAUSAL BLEEDING - A STRONG INDICATOR OF ENDOMETRIAL CARCINOMA.
Keywords: Atrophic endometrium, Endometrial carcinoma, Postmenopausal bleeding, Transvaginal ultrasound.
Menopause is defined as the last menstrual period after a minimum of one year's amenorrhoea1. There is no mutual consensus for deciding the appropriate interval of amenorrhoea which will precede an episode of vaginal bleeding due to the anovulatory cycles that precedes menopause2. It is estimated that 1-25% and on the average 10% women who present to the clinicians with postmenopausal bleeding will be ultimately diagnosed with endometrial carcinoma. Endometrial atrophy is the most common cause amongst the postmenopausal women. Endometrial polyps and hyperplasia are other common causes3.
In the US, endometrial cancer is the most commonly diagnosed reproductive tract malignancy and is the fourth most common cancer among women, superseded by cancers of breast, lung and colorectal origin. Although it is responsible for causation of 6% of female malignancies, its ease of diagnosis and timely therapy makes it responsible for only 3% of malignancy related deaths4. There are two types of endometrial carcinomas, type I is secondary to unopposed estrogen induced endometrial hyperplasia and type II are serous or clear cell origin, are independent of estrogen stimulation and have relatively poor prognosis5. Recent data shows that type I comprises 90% and type II comprises 10% of endometrial malignancies6.
For women receiving hormone replacement therapy, the pattern of bleeding depends on the type of gonadal steroids, especially the progestogens. Break through bleeding occurs in women taking estrogen alone or both estrogen and progestogens. Fifty percent of women on hormone replacement therapy (HRT) experience breakthrough bleeding. In women with uterus, systemic estrogens of HRT increase the risk of endometrial carcinomas, even after its use is stopped. For postmenopausal women not taking HRT, risk of endometrial carcinoma is 4.9% to 11.5%7.
Risk factors for endometrial carcinoma are obesity, hypertension and hyperestrogenism (exogenous or endogenous)8. Early menarche, late menopause and nulliparity due to high frequency of anovulatory cycles is also a risk factor. Hereditary non polyposis colorectal cancer is a rare risk factor with relatives of an affected family member having 50% risk of endometrial cancer9.
Transvaginal ultrasonography is used to measure thickness of endometrium. This should be thinner in post menopausal women (70 years###2###5.7
Table-II: Patterns of postmenopausal bleeding (n=35).
Frequency of Bleeding
Table-III: Etiology of postmenopausal bleeding on the basis of histopathological reports (n=35).
Atypical Endometrial Hyperplasia###5###14
Her histopathology reports and cervical smear results were followed in the OPD.
Data collected and analyzed in SPSS version 20.0. Mean and standard deviation calculated for numerical data and frequencies and percentages calculated for categorical variables. All data presented in the form of tables.
A total of 35 women were recruited into the study. Four age groups were created and subjects allocated into each group. Five (14%) subjects were between 45-51 years age, 9 (25.7%) women were 52-60 years age, 19 (54.3%) were 61-70 years and 2 (5.7%) were more than 70 years age. Mean age was 62 +- 2.54 years.
Seven (20%) women had diabetes and 12 (35%) were hypertensive. Eleven (31.4%) women were nulliparous and 24 (68.57%) were multiparous (table-I).
Twenty (57%) women complained of a streak of blood on pad when asked about the amount of bleeding. Eight (23%) said it was mere spotting and in case of 7 (20%), it was heavy bleeding with soaking of full sanitary pad. Seven (20%) subjects had a single episode of per vaginal bleeding and 28 (80%) had this complaint for multiple times before they sought medical advice (table-II).
Amongst the etiology, benign causes were more common when histopathological reports were reviewed. Atrophic endometrium was the most common, being seen in 9 (26%) subjects, followed by chronic endometritis in 8 (23%), polyp in 4 (11.4%) and proliferative endometrium in 1 (2.8%) cases. Amongst the premalignant and malignant etiologies, endometrial carcinoma was seen in 8 (23%), atypical endometrial hyperplasia in 5 (14%) and cervical carcinoma was seen in 1 (2.8%) case of postmenopausal bleeding. Commonest type of endometrial carcinoma seen was endometroid carcinoma seen in 28 (80%) subjects (table-III).
In our study, 22 (63%) subjects had time period of less than 10 years between menopause and initiation of postmenopausal bleeding, but the risk of malignancy increased with increasing interval between menopause and development of symptoms.
The main objective in managing a patient with postmenopausal bleeding is to exclude malignancy. Although 80-90% of patients presenting with this complaint had benign etiology, premalignant and malignant causes must be ruled out.
The commonest age group seen in our study was 61-70 years age, with mean age being 62 +- 2.54 years. Our result correlates with the study done by Burbos et al where the mean age was 64 years12 and the studies done by Davis et al by Von Doorn et al in terms of common age group12-14. Regarding parity, 68.57% of our patients were multiparous. Nulliparity has been considered to be a risk factor for endometrial carcinoma not because of tself but due to the anovulatory cycles in infertile subjects. In a study done by Kothapally et al at Andhra Pradesh, India, it was concluded that most of the women with post-menopausal bleeding with ultimate histopathological findings of endometrial carcinoma were multiparous15.
Diabetes was co-morbidity in 20% of our studied population. Burbos et al reported the figure around 17%12 and Visser et al reported it as 12.9%16, whereas it was present in 54.5% of women studied by Fatima et al at Khyber Teaching Hospital, Peshawar17. Food with high carbohydrate contents, hyper insulinemia, resistance to insulin and high levels of insulin like growth factors are related to division of endometrial cells thus leading to endometrial carcinoma18. Hypertension was seen in 35% cases in our study. This is in accordance with different national and international studies where figures of 34.4% and 27.3% were seen16,17,19.
Most of our patients (57%) presented with a light episode of vaginal bleeding. This much amount of bleeding was reported by 55% of subjects in a study done at Norwich, UK in 201012, whereas frequency were reported as recurrent in the same study in 76% cases, close to our study (80%).
Regarding the histopathological reports of these patients, we observed that 26% of our cases had atrophic endometrium, followed by chronic endometritis in 23% cases. Similar findings have been reported by different authors in their studies15,20,21. The reason might be that the very weak and fragile support of blood vessels which is provided by stromal tissue leads to hemorrhages and ulcerations in mucosal lining and may also lead to infection (endometritis)22. Polyps were seen in 11.4% cases in our study, which is in contrast to the study by Fatima et al where they reported 26% cases of postmenopausal bleeding due to polyps17. Banfa et al reported close figures to ours whereas it was high in a study conducted by Ghoubara et al in 201823,24.
In the premalignant and malignant etiologies, atypical endometrial hyperplasia was seen in 14% cases. Brand et al reported similar results and it has been suggested that atypical endometrial hyperplasia is indeed a trouble some finding as it precedes the development of endometrial carcinoma or may be harboring it at that time20. Endometrial carcinoma was seen in 23% of our study population, whereas it was responsible for causation of postmenopausal bleeding in 16% subjects in the study conducted by Jillani et al and 11% in study conducted by Ghazi et al25,26. These are relatively lower figures as compared to ours. Yousaf et al in their study at Lady Willingdon Hospital, Lahore have reported 30.5% incidence of endometrial carcinoma in patients presenting with postmenopausal bleeding27.
The commonest type of endometrial carcinoma seen in our study was endometroid type (80%) which is close to that seen by Fatima et al in their study (81.8%)17 but contrary was seen in a study done in 2018 at Ankara, Turkey where only 10% women were found to have endometroid type of carcinomas28.
Considering the limitations in our study like small sample size, hospital based survey and lack of follow up by some patients, the results, however, cannot be generalized for the whole population.
Postmenopausal bleeding is an alarming symptom and should be thoroughly investigated with transvaginal ultrasound followed by endometrial biopsy for timely diagnosis and treatment.
CONFLICT OF INTEREST
This study has no conflict of interest to be declared by any author.
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|Publication:||Pakistan Armed Forces Medical Journal|
|Date:||Apr 30, 2019|
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