scholarly journals Markers of human endometrial hypoxia can be detected in vivo and ex vivo during physiological menstruation

2021 ◽  
Author(s):  
J J Reavey ◽  
C Walker ◽  
M Nicol ◽  
A A Murray ◽  
H O D Critchley ◽  
...  

Abstract STUDY QUESTION Can markers of human endometrial hypoxia be detected at menstruation in vivo? SUMMARY ANSWER Our in vivo data support the presence of hypoxia in menstrual endometrium of women during physiological menstruation. WHAT IS KNOWN ALREADY Current evidence from animal models and human in vitro studies suggests endometrial hypoxia is present at menstruation and drives endometrial repair post menses. However, detection of human endometrial hypoxia in vivo remains elusive. STUDY DESIGN, SIZE, DURATION We performed a prospective case study of 16 women with normal menstrual bleeding. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductively aged female participants with a regular menstrual cycle underwent objective measurement of their menstrual blood loss using the alkaline haematin method to confirm a loss of <80 ml per cycle. Exclusion criteria were exogenous hormone use, an intrauterine device, endometriosis or fibroids >3 cm. Participants attended for two MRI scans; during days 1–3 of menstruation and the early/mid-secretory phase of their cycle. The MRI protocol included dynamic contrast-enhanced MRI and T2* quantification. At each visit, an endometrial sample was also collected and hypoxia-regulated repair factor mRNA levels (ADM, VEGFA, CXCR4) were quantified by RT-qPCR. MAIN RESULTS AND THE ROLE OF CHANCE Women had reduced T2* during menstrual scans versus non-menstrual scans (P = 0.005), consistent with menstrual hypoxia. Plasma flow (Fp) was increased at menstruation compared to the non-menstrual phase (P = 0.0005). Laboratory findings revealed increased ADM, VEGF-A and CXCR4 at menstruation on examination of paired endometrial biopsies from the menstrual and non-menstrual phase (P = 0.008; P = 0.03; P = 0.009). There was a significant correlation between T2* and these ex vivo hypoxic markers (P < 0.05). LIMITATIONS, REASONS FOR CAUTION This study examined the in vivo detection of endometrial hypoxic markers at specific timepoints in the menstrual cycle in women with a menstrual blood loss <80 ml/cycle and without significant uterine structural abnormalities. Further research is required to determine the presence of endometrial hypoxia in those experiencing abnormal uterine bleeding with and without fibroids/adenomyosis. WIDER IMPLICATIONS OF THE FINDINGS Heavy menstrual bleeding (HMB) is a common, debilitating condition. Understanding menstrual physiology may improve therapeutics. To our knowledge, this is the first in vivo data supporting the presence of menstrual hypoxia in the endometrium of women with normal menstrual bleeding. If aberrant in those with HMB, these non-invasive tests may aid diagnosis and facilitate personalized treatments for HMB. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by Wellbeing of Women grant RG1820, Wellcome Trust Fellowship 209589/Z/17/Z and undertaken in the MRC Centre for Reproductive Health, funded by grants G1002033 and MR/N022556/1. H.O.D.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc; Myovant Sciences GmbH. H.O.D.C. receives royalties from UpToDate for articles on abnormal uterine bleeding. TRIAL REGISTRATION NUMBER N/A.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4777-4777
Author(s):  
Susan Halimeh ◽  
Lava A. Talat Sharief ◽  
Andrew S. Lawrie ◽  
Guenther Kappert ◽  
Ian J. Mackie ◽  
...  

Introduction Factor XIII (FXIII) has an important role in the control of bleeding through fibrin cross-linking. While many physiological factors affect plasma FXIII level, the effect of the menstrual cycle is not fully understood.Aim: The study aimed to assess possible changes in plasma FXIII activity during the normal menstrual cycle and to assess any correlation between FXIII activity during the menstrual phase and the menstrual blood loss. Methods In this longitudinal study, a total of 32 women of reproductive age were recruited. Menstrual blood loss was measured using the pictorial blood-assessment chart (PBAC). A bleeding questionnaire and score were also completed. Blood samples were taken during menstrual phase (day 1-5), proliferative phase (day 6-11), periovulatory phase (day 12-17), secretory phase (days 18-23), and premenstrual phase (day 24-29) for assessment of FXIII level using quantitative ammonia release assay. Results Mean FXIII level was significantly lowest during menstrual and periovulatory phases of the cycle (114 IU/dL) compared to secretory (121 IU/dL) and premenstrual (122 IU/dL) phases (p=0.036). No significant correlation between FXIII activity during menstrual phase and women age (p= 0.53) or PBAC score (p=0.53). Among 14 women with PBAC score ≥ 100, the median FXIII activity during the menstrual phase of the cycle was 116 IU/dL, this was not statistically different from group with PBAC score <100 (113 IU/dL) (p = 0.72). Conclusion FXIII activity was lowest during the menstrual and periovulatory phases of the cycle. Understanding these changes in FXIII during menstrual cycle will help clinicians to perform blood tests during appropriate phase of the menstrual cycle and to capture the baseline level. Disclosures: Halimeh: Octapharma AG: Investigator Other, Research Funding.


Author(s):  
Khushboo Jha ◽  
K. Bharathi ◽  
Sonu

Any uterine bleeding outside the normal volume, duration, regularity or frequency is considered as abnormal uterine bleeding (AUB). Nearly thirty percent of all gynaecological outpatient attendants are for AUB. Abnormal menstrual bleeding pattern have been traditionally expressed by terms like menorrhagia, metrorrhagia, polymenorrhagia & oligomenorrhoea. Normal menstrual cycle interval is 28 days (21-35 days), menstrual flow duration 4-5 days and normal menstrual blood loss should be 35ml (20-80 ml). Any deviation in the above criteria comes under abnormal uterine bleeding, means excessive amount of bleeding or increased duration of bleeding during menstruation or both termed as AUB. In Ayurveda same is described as Pradara. A female patient aged 22 years visited OPD of Prasuti Tantra and Stri Roga department of NIA, with complaints of heavy menstrual bleeding and prolonged menstrual bleeding more than seven days since six months. Pictorial blood loss assessment chart was used to assess the amount of blood loss before and after treatment. SF-36 questionnaire was assessed to know the improvement in quality of life. Patient was given Kutajashtakaleha 10 gm BD with cows milk.


Author(s):  
Sabah Malik ◽  
Saba Musharaf ◽  
Fidah Malik ◽  
Mohd Abass

Background: The term dysfunctional uterine bleeding (DUB) is used for abnormal uterine bleeding occurring in the absence of identifiable pathology. A number of drugs are available for management of DUB- nonsteroidal anti-inflammatory drugs, tranexamic acid, ethamsylate, hormones like Oral contraceptives progestins etc. The present study was done to determine the efficacy and safety of ormeloxifene in the management of DUB.Methods: This prospective clinical study involved 50 cases with DUB who were treated with ormeloxifene 60 mg tablet twice a week for first 12 weeks and the once a week for next 12 weeks. They were followed after 6 months of therapy. The outcome was studied by assessment of menstrual blood loss by PBAC score, Hb level in g/dl, endometrial thickness in mm, relief of dysmenorrheal and any side effects of drugs.Results: The median PBAC score was significantly reduced from 316 to 52 after 6 months of therapy. The mean Hb concentration was significantly increased from 7.8 g/dl to 9.1 g/dl at 6 months of therapy. The mean endometrial thickness was reduced from 10 mm to 7.9 mm after 6 months of therapy. 66% of women showed marked subjective improvement in symptoms. Amenorrhea was the main side effect (12%).Conclusions: Ormeloxifene has significant effect in reducing endometrial thickness, decreasing the amount of menstrual blood loss, reducing dysmenorrhea and thereby improving the general condition of the patient. It is definitely a better alternative to hysterectomy in women who wish to avoid surgeries and maintain their reproductive functions.


1987 ◽  
Vol 113 (2) ◽  
pp. 291-295 ◽  
Author(s):  
M. C. P. Rees ◽  
V. Di Marzo ◽  
J. R. Tippins ◽  
H. R. Morris ◽  
A. C. Turnbull

ABSTRACT Endometrium and myometrium were collected at hysterectomy from 21 women with measured menstrual blood loss. Eight women complained of dysmenorrhoea and the remaining 13 had pain-free periods. Specimens were obtained throughout the menstrual cycle (menstrual, n = 5; follicular, n = 3; early luteal, n = 3; mid-luteal, n = 5; late luteal, n = 4). Leukotriene C4, leukotriene D4 and leukotriene E4 release were examined using a short-term incubation technique. Endometrial leukotriene release, which was always significantly greater than myometrial release, changed throughout the menstrual cycle and the highest concentrations were found during menstruation. Endometrial, but not myometrial, leukotriene concentrations were significantly higher in tissues obtained from women with a complaint of dysmenorrhoea compared with those in tissue from pain-free women. No correlation was found between leukotriene release in either endometrium or myometrium and menstrual blood loss (range 15–457 ml). J. Endocr. (1987) 113, 291–295


2020 ◽  
Author(s):  
Yunhui Tang ◽  
Yan Chen ◽  
Hua Feng ◽  
Chen Zhu ◽  
Mancy Tong ◽  
...  

Abstract Background: Irregular menstrual cycles including the length of cycles and menses, and heavy menstrual blood loss are linked to many gynaecological diseases. Obesity has been reported to be associated with irregular menstrual cycles. However, to date, most studies investigating this association are focused on adolescence or university students. Whether this association is also seen in adult women, especially women who had a history of birth has not been fully investigated. Methods: Questionnaire data were collected from 1012 women aged 17 to 53 years. Data on age, weight and height, gravida, the length of menstrual cycles and menses, and the number of pads used during menses were collected. Factors associated with menstrual cycle according to BMI categories were analysed.Results: There were no differences in the length of menstrual cycles and menses in women of different body mass index (BMI) groups. However, there was a significant difference in menstrual blood loss in women of different BMI categories. The odds ratio of having heavy menstrual blood loss in obese women was 2.28 (95% CL: 1.244, 4.193), compared to women with normal weight, while there was no difference in the odds ratio of having heavy menstrual blood loss in overweight, compared to normal weight, women. In contrast, the odds ratio of having heavy menstrual blood loss in underweight women was 0.4034 (95% CL: 0.224, 0.725), compared to women with normal weight. Conclusion: Although BMI was not correlated with the length of menstrual cycle and menses, BMI is positively associated with menstrual blood loss. Our data suggest that BMI influences menstrual blood loss in women of reproductive age and weight control is important in women’s reproductive years.


2020 ◽  
Vol 11 (4) ◽  
pp. 5678-5684
Author(s):  
Swathi Suresh ◽  
Mariya Els Johny ◽  
Kiruba Shankari ◽  
Ahamed Irshath U ◽  
Yokesh M ◽  
...  

Dysfunctional uterine bleeding is a type of abnormal uterine bleeding where vaginal bleeding occurs outside of the menstrual cycle in the absence of any known pelvic pathology. Dysfunctional uterine bleeding can be treated safely with hormone therapy. Combined oral contraceptives help in increased menstrual cycle regularity and decreased blood loss. In this study, a reliable drug for the dysfunctional uterine bleeding with maximum effectiveness and minimal side effects were assessed. This study was conducted on 120 cases of dysfunctional uterine bleeding. Patients who were diagnosed with dysfunctional uterine bleeding were randomly assigned into two groups. Group D and group L included patients who were given Ethinyl estradiol 0.02mg + desogestrel 0.15mg and Ethinyl estradiol 0.03mg + levonorgestrel 0.15mg respectively for the four consecutive 28- day cycles. Menstrual blood loss was assessed using the pictorial blood assessment chart (PBAC) score on 2nd and 4th months of recruitment. Side effects such as weight gain, acne and headache were assessed in both groups. This study shows 56.68% reduction in mean PBAC score in 2 months in desogestrel group whereas only 44.96% reduction in levonorgestrel group and 79.87% reduction in mean PBAC score in desogestrel group in 4 months whereas only 74.46% reduction in levonorgestrel group. Side effects like weight gain, acne and headache were more prominent in the levonorgestrel group than desogestrel group. Desogestrel containing combined oral contraceptive can be a useful and safe treatment for dysfunctional uterine bleeding.


2021 ◽  
Vol 04 (11) ◽  
pp. 97-99
Author(s):  
Sonu Kumari ◽  
Mahesh Dixit ◽  
Narendra Kumar Meena

In PrasutitantraOPD, Menometrorrhagia is the most common gynaecological illness. It is a symptom that can be detected in the majority of gynecological issues. The irregular, massive blood loss per vaginum is a symptom of abnormal uterine bleeding. Bleeding in excess of regular amounts and for a longer period of time during the menstrual cycle. Abnormal uterine bleeding is known as Asrigdara in Ayurvedic samhitas, which implies pradirana(extreme excretion) of raja (menses) per vaginum. The causative factor or Dosa In Asrigdarais Vayu, and the vitiated Dhatu Or Dusya is Rakta(blood), or blood is also vitiated. Because the qualities of rakta and pittaare so similar, vitiating Raktawould aggravate pitta as well. As a result, management should be centered on the usage of medications with Kashaya Rasa and Pittashamak Guna.Due to its Stambhanafeature, Kashaya rasais mostly used to treat bleeding symptoms.There is loss of Rakta Dhatu, so we use the drugs and diet that increases Rakta Dhatu.Management mainly based on the principle of Raktastambhakaand Raktavardhaka.


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