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ORIGINAL ARTICLE
Year : 2012  |  Volume : 26  |  Issue : 3  |  Page : 167-170

The histological and histochemical study of endometrium in dysfunctional uterine bleeding


1 Department of Pathology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Obstetrics and Gynaecology, Regional Institute of Medical Sciences, Imphal, Manipur, India
3 Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication10-Jun-2013

Correspondence Address:
L Sushila Devi
Department of Pathology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-4958 .113240

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  Abstract 

Objective: To evaluate the histology and histochemistry of endometrium in dysfunctional uterine bleeding (DUB). Materials and Methods: This was a prospective study conducted in Regional Institute of Medical Sciences, Imphal during the period between 1 st December 2004 and 31 st August 2006. A total of 50 cases of DUB and another ten matched normal subjects were selected. Endometrial samples taken between the 21 st and the 24 th day of the menstrual cycle and at random for continuous vaginal bleeding were studied with conventional H and E, periodic acid schiff and alcian blue stains. Results: Endometrial patterns of DUB were proliferative (44%), secretory (20%), irregular ripening (14%), atrophic endometrium (18%) and irregular shedding (4%), respectively. Conclusion: The commonest types of endometrium in DUB are proliferative and secretory endometrium is seen in all the normal subjects.

Keywords: Anovulation, Dysfunctional uterine bleeding, Histochemical stains


How to cite this article:
Devi L S, Singh M R, Singh L R, Debnath K. The histological and histochemical study of endometrium in dysfunctional uterine bleeding. J Med Soc 2012;26:167-70

How to cite this URL:
Devi L S, Singh M R, Singh L R, Debnath K. The histological and histochemical study of endometrium in dysfunctional uterine bleeding. J Med Soc [serial online] 2012 [cited 2020 Oct 31];26:167-70. Available from: https://www.jmedsoc.org/text.asp?2012/26/3/167/113240


  Introduction Top


Dysfunctional uterine bleeding (DUB) is uterine hemorrhage that occurs at irregular intervals in excessive or scant amount especially, when prolonged and when there is no easily assignable cause such as polyps and hyperplasia, neoplasm, blood dyscrasia, pregnancy or hormone administration. Polycystic ovarian diseases, stress, crash diet, and vigorous exercise can disrupt normal ovulatory function though scientific ideas are rapidly changing as to the underlying cause of DUB, but undoubtedly there is dysfunction in the hypothalamo-pituitary-ovarian axis. [1] It usually affects 5% of menstruating women. [2] Majority of the cases of DUB occurs in perimenopausal women or after menarche when the ovaries are in unstable responsive stage. Abnormal secretion of both estrogen and progesterone occurs in this group of women.

Anovulatory cycles are the most common cause of DUB of the women of reproductive age. DUB associated with ovulatory bleeding is poorly understood. However, disordered prostaglandin metabolism and increased lysosomal activity in the endometrial cells explain most cases of ovulatory DUB. In a large proportion of women, the basic disorder may be pituitary overproduction of Prolactin, which in excess suppresses progesterone production. Rarely, endometrium lacks progesterone receptors. [3] DUB may also be due to local factors like abnormal platelet aggregation caused by a shift in prostaglandin synthesis.

Iatrogenic etiologies include, use of hormone therapy, contraceptive injection, and devices; and medications including, tranquilizers, antidepressants, anticoagulants, and corticosteroids. Systemic diseases are another group to consider that includes, coagulation disorders (thrombocytopathies, von Willibrand's disease and leukaemia), hypo-thyroidism, systemic lupus erythematosus, and cirrhosis of liver.


  Materials and Methods Top


The study was conducted in the Departments of Obstetrics and Gynecology and Pathology, Regional Institute of Medical Sciences, Imphal during 1 st December 2004 to 31 st August 2006. A total number of 50 cases of DUB in the age group of 18-50 years were selected (group B). Ten age-matched normal cases were also studied as controls (group A). In the study group, a thorough clinical examination including, ultrasonography evaluation of uterus, complete hematological profile including platelet count and computed tomography were carried out. Thyroid function tests (T3, T4 and thyroid stimulating hormone (TSH) and blood sugar (random) were also carried out. Endometrial biopsies were performed between 21 st and 24 th day of the menstrual cycle and at random for cases with continuous vaginal bleeding and endometrial tissues were collected in two samples in each case. One sample was preserved in formol saline and processed for conventional H and E, periodic acid schiff (PAS) and alcian blue stains. PAS reaction detects droplets of glycogen and alcian blue stain detects acid mucopolysaccharides in the glandular epithelium of the secretory phase of endometrium. The cut sections from the unfixed sample prepared using cryostat were stained for alkaline phosphatase (azo-dye coupling method using alpha napthyl phosphate) which detects the activity of alkaline phosphatase during the proliferative phase of endometrium.


  Results and Observations Top


Of the 50 cases of DUB studied, the highest numbers of patients were in the age group of 36-45 years (54%) [Table 1]. It was also observed that DUB was common both among nullipara as well as women with high parity. The common symptoms were metrorrhagia (38%), followed by menorrhagia (34%), polymenorrhea (24%), and post-menopausal bleeding (4%).
Table 1: Age distribution of control and study cases

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Fifty percent of the cases of DUB were anemic at the time of initial attendance at the hospital. Forty four percent of the patients had Hb% in the range of 10.1-12 g%, 38% in the range of 8.1-10 g% and 12% in the range of 6.1-8 g%.

Endometrial histology by H and E stain showed late proliferative phase endometrium in 30% of the cases followed by atrophic endometrium (18%) and early proliferative and irregularly ripened endometrium having 14% each in the study group [Table 2] and late secretory endometrium was observed in all cases in the control group. The stromal changes in the endometrium including, angiogenesis (19%), fibrin clot in blood vessel (4%), thick walled blood vessel (6%) and inflammatory cell infiltration (2%) were discerned in the late proliferative endometrium in our study.
Table 2: Endometrial histology of the cases (H and E)

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Comparative study of endometrial histology by H and E stain and special stains (PAS, alcian blue, and alkaline phosphatase) were also carried out. The cases in the late secretory and irregular shedding showed the same result in both H and E and PAS stain [Figure 1]. In irregular ripening, 71.4% of patients with positive H and E stain showed positive PAS stain. Half of the early secretory endometrium with H and E stain showed positive PAS stain. Comparison of H and E stain and alcian blue stain [Figure 2] showed maximum concordance in irregular shedding (100%) followed by late secretory (83.3%) and irregular ripening (57.1%) [Figure 3]. In early secretory 50% of cases with positive H and E stain showed positive alcian blue stain. PAS and alcian blue stains were negative in proliferative and atrophic endometrium [Table 3] and [Table 4].
Figure 1: Photomicrograph of secretory endometrium (PAS stain, ×40)

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Figure 2: Photomicrograph of secretory endometrium (alcian blue stain, ×10)

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Figure 3: Photomicrograph of irregular ripening of endometrium (alcian blue stain, ×10)

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Table 3: Endometrial histochemistry of the cases (PAS stain)

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Table 4: Endometrial histochemistry of the cases (alcian blue stain)

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Of the seven cases of early proliferative and 15 cases of late proliferative endometrium by H and E stain, one case in early proliferative and 10 cases in late proliferative endometrium showed positivity for alkaline phosphatase in the stroma, but in the remaining cases it was negative [Table 5].
Table 5: Endometrial histochemistry of the cases (alkaline phosphatase stain)

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All the cases in this study had evaluation of thyroid function tests (T3, T4 and TSH and only six cases had low-levels of T3 and T4, but normal TSH level. Random blood sugar estimation was also carried out in all the subjects. Two patients had glucose levels of 150 mg/dl and 152 mg/dl. However, subsequent glucose tolerance test showed normal findings.


  Discussion Top


DUB is most often the result of unopposed estrogen stimulation of the endometrium with consequent irregular breakdown and bleeding. Although, the most frequent cause is anovulation, histologic study consistently showed that 15-20% have secretory endometrium indicative of at least intermittent if not regular ovulation.

In the present study, most of the patients belong to the age group of 31-45 years, maximum being in the age group of 36-40 years (34%), which correlates with the study of Agarwal et al. [4] and Matah et al. [5] It was also more commonly found in nulliparous than multiparous women. The commonest presenting symptom is metrorrhagia followed by menorrhagia, polymenorrhea and post-menopausal bleeding. Ninety four percent of the patients had hemoglobin of less than 12 g%. The apparent cause of anemia in these patients is due to chronic blood loss without supplements of hematinics. Only 6% of the cases had normal hemoglobin level at presentation.

Anovulatory cycle was observed in 62% of the cases and 38% of the cases showed ovulatory cycles. Of the patients with anovulatory cycles 44% showed early and late proliferative endometrium. 18% showed atrophied gland and 8% showed deficient endometrial secretion. This findings may be comparable to the study of other workers. [6],[7] Though, angiogenesis (observed in 10% of the cases studied) is an important event in cycle regulation in normal and pathological endometrium, [8] its precise role in the etio-pathogenesis of DUB is not clear. Vascular changes in proliferative anovulatory endometrium has also been reported by many workers in their studies. [9],[10] Thick walled blood vessels (observed in 6% of the cases) may fail to contract to control bleeding by detaching themselves more slowly producing irregular and prolonged menstrual bleeding thereby providing a role of vascular abnormality in the etiology of DUB.

Further in the absence of progesterone exposure to cause inhibition of deoxyribonucleic acid synthesis and mitosis, the estrogenic proliferative response causes stromal cell growth to exceed the structural integrity of the stromal matrix and the endometrium breaks down with irregular bleeding. In the absence of normal control mechanism to limit blood loss, the bleeding tends to be prolonged and excessive.

Excessive blood loss in DUB may be due to multiple factors. A shift to endometrial conversion of prostaglandin endoperoxidase from prostaglandin (PGF2-alpha) to prostaglandin (PG) E2, reduced prostaglandin production and reduced availability of arachidonic acid, [11] changes in the production of prostacyclin, thromboxane, and increased fibrinolytic activities; [12] all these factors seem to have a role in DUB. Inflammatory changes in the anovulatory endometrium was observed in 2% of the cases, which correlates with findings by other workers. [13],[14]

DUB in otherwise normal ovulatory endometrium is really perplexing. Endometrial estrogen and progesterone levels are higher in the late secretory phase in women with DUB [15] and there is a strong positive correlation between the level of endometrial estrogen receptor in late secretory endometrium and the amount of blood loss.

In the present study, only six cases (12%) showed low T3 and T4 with normal TSH levels. Isolated decreased T3 and T4 levels without any increase in TSH level and clinical features of hypothyroidism may be a coincidental finding. Random blood sugar estimation in all the 50 cases showed no significant finding except in two cases that had initial increased blood sugar levels which were subsequently found to be normoglycemic by glucose tolerance tests.


  Conclusion Top


DUB is a common gynecological problem in women of reproductive age group and 20% of women with DUB will seek medical consultation. Anovulation with unopposed estrogen activity as indicated by histological and histochemical analysis of the cases was the most common finding. Anovulatory DUB is commonly observed at both the extremes of reproductive age group and is because of immaturity of hypothalamo-pituitary-ovarian axis and changes associated with menopause. The associated stromal changes in the late proliferative phase are also implicated in the pathogenesis of DUB even though it needs further study in larger series. Secretory endometrium is a less common finding in the present study. The mechanism of ovulatory DUB is less well-understood and hormonal imbalance seems to be the primary cause in the pathogenesis. The histological and histochemical studies of endometrium in DUB reveal the type of functional disturbances and definitely assist in the proper management of the patients.

 
  References Top

1.Mitra K, Chowdhury MK. Histological and histochemical study of endometrium in dysfunctional uterine haemorrhage. J Indian Med Assoc 2003;101:484-5.  Back to cited text no. 1
    
2.Wren BG. Dysfunctional uterine bleeding. Aust Fam Physician 1998;27:371-7.  Back to cited text no. 2
    
3.Laatikainen T, Andersson B, Kärkkäinen J, Wahlström T. Progestin receptor levels in endometria with delayed or incomplete secretory changes. Obstet Gynecol 1983;62:592-5.  Back to cited text no. 3
    
4.Agarwal U, Sharma S, Tripathi S. Endometrial aspiration cytology versus biopsy in women with abnormal uterine bleeding. J Obstet Gynecol India 1986;36:719-21.  Back to cited text no. 4
    
5.Matah M, Singh NN, Baral J, Tiwari P, Gupta S, Sahader S. Role of uterine aspiration cytology above thirty years. J Obstet Gynecol India 1993;43:804-7.  Back to cited text no. 5
    
6.Vakiani M, Vavilis D, Agorastos T, Stamlo Poulos P, Assimaki A, Bontis J. Histological findings of the endometrium in patients with DUB. Clin Exp Obstet Gynecol 1996;23:236-9.  Back to cited text no. 6
    
7.Zlatkov V, Radeva V, Cholakova G, Mikhova A, Bŭrzakov G, Velinov E, et al. Assessment of irregular uterine bleeding in premenopausal women. Akush Ginekol (Sofiia) 2002;41:33-5.  Back to cited text no. 7
    
8.Abulafia O, Sherer DM. Angiogenesis of the endometrium. Obstet Gynecol 1999;94:148-53.  Back to cited text no. 8
    
9.Bhargava H, Gupta S. The role of vascular architecture of the endometrium in the aetio-pathogenesis of dysfunctional uterine bleeding. J Obstet Gynecol India 1979;29:1241-5.  Back to cited text no. 9
    
10.Salvatore CA. Arteriole alteration in normal and hyperplastic endometrium. Am J Obstet Gynecol 1968;102:493- 500-10.  Back to cited text no. 10
    
11.Smith SK, Abel MH, Kelly RW, Baird DT. Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding. Br J Obstet Gynaecol 1981;88:434-42.  Back to cited text no. 11
    
12.Sheppard BL. The pathology of dysfunctional uterine bleeding. Clin Obstet Gynaecol 1984;11:227-36.  Back to cited text no. 12
    
13.Moghal N. Diagnostic value of endometrial curettage in abnormal uterine bleeding: A histopathological study. J Pak Med Assoc 1997;47:295-9.  Back to cited text no. 13
    
14.Rao SS, Savathi C, Lalithakumari B, Venkaratnami G. Endometrial aspiration cytology in DUB. J Obstet Gynecol India 1986;36:334-7.  Back to cited text no. 14
    
15.Gleeson N, Jordan M, Sheppard B, Bonnar J. Cyclical variation in endometrial oestrogen and progesterone receptors in women with normal menstruation and dysfunctional uterine bleeding. Eur J Obstet Gynecol Reprod Biol 1993;48:207-14.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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