A comparison Between the Effect of Metformin and Progesterone on the Endometrium in cases of peri menopausal bleeding

DISCUSSION

According to patient characteristics between studied groups, there was no statistically substantial difference between the two studied groups. In group 1 Mean &SD for age was 47.28±2.28, for BMI (kg/m2) was34.03±4.29, for Gravidity was 4.08±1.12, for Parity was 3.7±0.94 & for Abortion was 1.11±0.60.

 In group 2 mean and SD for age was 46.04±2.39, for BMI (kg/m2) was 3.91±0.98, for Gravidity was 3.91±0.98, for Parity was 3.5±1.05& for Abortion was 1.14±0.38.

According to the outcome among studied groups there was no statistically significant difference between the two studied groups regarding uterine bleeding after treatment (p= 0.47), endometrial thickness after treatment (P= 0.706). Also, there was no statistically big difference between the two studied groups as regards patient’s satisfaction and hysterectomy. The duration of treatment didn’t differ between the two groups all have three months duration.

In group 1 Abnormal Uterine Bleeding before treatment was Heavy in all cases but after treatment it was heavy in only 21 (42.0%) and controlled in 29 (58.0%). According to ET before treatment of mean 16.04. However after treatment Mean & SD was 11.01 ± 5.21. Satisfied patients were 44 (88.0%) and 6 (12.0%) were not satisfied. Hysterectomy done in 6 (12.0%) of cases. treatment duration per weeks reached 12.02 with SD of 0.98.

In group 2 Abnormal Uterine Bleeding before treatment was Heavy in all cases but after treatment it was heavy in only 19 (38.0%) and controlled in 31 (62.0%). According to ET before treatment of mean 15.06. However after treatment Mean & SD was 10.26 ± 4.25. Satisfied patients were 46 (92.0%) and 4 (8.0%) were not satisfied. Hysterectomy done in 4 (8.0%) of cases. treatment duration per weeks reached 11.84 with SD of 1.42.

In Elgarhy et al.⁸ according to gravidity, no statistical significant difference was found between Metformin with Mean of 3.64 & SD of 1.83 and Progesterone groups with mean of 3.46 and SD of 1.67. No statistical significant difference was found between Metformin with Mean of 2.96 & SD of 1.74 and Progesterone groups with mean of 3 and SD of 1.47.

According to our study, In Metformin group about one third (32%) of patients had simple hyperplasia and the remaining (68%) had disordered proliferative endometrium. However, in progesterone group 28% of patients in the progesterone group had simple hyperplasia and the remaining 72% had disordered proliferative endometrium.

According to response to medication in metformin and progesterone groups, 82% of patients and 86% of patients in the progesterone group showed positive response to medication with no statistical significant reference.

After treatment in the metformin group, 11 out of 16 patients (68.8%) with simple hyperplasia transformed into atrophic endometrium whereas, 25 out of 34 patients (73.5%) with disordered proliferative endometrium transformed into atrophic endometrium. After treatment in the progesterone group, 10 out of 14 patients (71.4%) with simple hyperplasia transformed into atrophic endometrium whereas, 26 out of 36 patients (72.2%) with disordered proliferative endometrium transformed into atrophic endometrium.

In our study, the patient that had ahysterectomy in first group 6 (12.0%) and in second group is 4 (8.0%) and that because of heavy bleeding that they don’t compliance with it ,pelvic pain associated with enodometriosis ,fibroid and adenomyosis that don’t correlate with the treatment, and to some patient the duration of study is too long to show its effect so looked forward to Hystrectomy operation .

Perfect responders should continue to receive cycling progesterone therapy, or a mix of cyclic and continual hormone replacement therapy if necessary. A three month study with MPA (10 mg orally 4 times per day) or megestrol acetate (80 mg orally five times per day) may be done if a partial response is achieved. Nonresponders and patients with intractabile  bleeding may benefit from a trans-abdominal hysterectomy. ⁹

In the revised classification for endometrial proliferative diseases and pre-cancerous lesions, DPE and EH without atypia were classified as benign, whereas aplasia (EIN) was classified as a real precancerous lesion with a substantial connection of coexistence or eventual uterine endometriod carcinoma. ¹⁰.

DPE and endo metrial hyperplasia without atypia were merged into benevolent categorization with no harmful effect, while endometrial intrepithelial neoplasia (EIN) was deemed a true precancerous sore with notable co-existance or subsequent uterine endometriod carcinoma, according to Wheeler et al.¹⁰.

After accounting for age, sex, A1c haemoglobin, hardship, smoking, and other drug use, Libby et al.¹¹ discovered that high glucose intolerance  patients who had taken  metformin had a disease rate that was much lower than diabetic patients who were never on metformin.

Our research found that group 1 had a higher statistically increased incidence of aching breasts, weakness, and metallic taste than group 2, while group 2 had a higher statistically increased incidence of nausea, vomiting, and diarrhoea than group 1.

Epigastric pain, headache, painful breast, weakness, and metallic taste were reported by 4, 12, 9, 49, and 50 individuals in group 1. In four patients, nausea, vomiting, and diarrhoea were reported. Headache, painful breast, weakness, and metallic taste were reported by 6, 1, 8, and 8 individuals in group 2. In 22 patients, nausea, vomiting, and diarrhoea were reported, but no epigastric pain was reported.

Cyclic progesterone-associated bleeding was substantially higher in Groups C and D than in Group A, according to Di Carlo et al.12 (194 (77.9%) and 163 (69.4%) vs. 125 (55.8%); p 50.01 and p 50.01, respectively). However, Group D scored significantly lower than Group C (163 (69.4%) vs. 194 (77.9%); p 50.05. Regular progesterone-related bleeding was also substantially more common in Group C than in Group B (194 (77.9%) vs. 145 (61.2%); p 50.01).

After controlling for age, sex, Alc haemoglobin, deprivation, smoking, and other drug use, Huang et al.13 discovered that cancer incidence in metformin-using diabetes patients was considerably lower than in non-metformin-using diabetic patients.

According to Huang et al.¹³, a possible component of metformine's anti-proliferative effect is that it initiates the AMPK pathway and improves AMPK enactment by LBK1, which leads to a reduction in cell vitality and tumour growth. 3 different  drugs (AMPK-activator) post poned carcinogenesis in tumor-prone animals, according to ongoing research centre confirmations. This finding suggests that AM P K activators may have a beneficial effect on cancer treatment  .

Zhang et al.⁹ revealed that metformin acts as a testosterone anta-gonist on endometrial glandular cell lines, implying that met formin could be use ful in resolving the insulin resistance impact of elevated androgen levels in PCO patients.

According to Yang et al.¹⁴, "Table S2 summarises adverse occurrences between the two groups. The most prevalent treatment-emergent side event was weight gain, which was reported by 34.2 percent of women in the metformin + MA group and 41.9 percent of women in the MA-only group.

The metformin + MA group gained 2.5 kg (1.0 to 6.0) on average during therapy, compared to 5.0 kg (0 to 10.0) in the MA-only group (P = 0.01). Nonetheless, grade 1–2 diarrhoea was more common in the metformin + MA group (15.8% versus 4.1 percent; P = 0.03) than in the MA-only group.

Other than diarrhoea, the metformin + MA group appeared to have a lower risk of side events than the MA-only group. When compared to the MA-only group, the metformin plus MA group had fewer patients with uterine haemorrhage (7.9% vs. 17.6%), increased nocturnal urine (0 vs. 4.1%), or breast pain (4.0 vs. 10.8%), though none of the intragroup differences were statistically significant ""It is philosophically significant."

The beginning of insulin/I G F-1 signalling through over expression of INSR and/or IGF-1R, the activation of PI3K/AKT/m.TOR signalling, and the loss of PTEN expression are all key processes in the patho genesis of human endo metrial atypical hyperplasia and E.C, according to Shao et al.15. In adding to it,s systemic properties, metformin's success in restoring early E.C to normal one  may be related to its anti-neoplastic effects on cellular metabolism and the AMPK and mTOR axis in the endometrium. Though important progress has been made in perceotion the possible molecular mechanisms behind metformin's therapeutic role in women with PCOS and EC, more research is needed into the regulatory mechanisms of metformin and their contribution to its anticancer activity before it can become a widely use for treating women with PCOS and early-stage EC.

CONCLUSION

Metformin, like progesterone, may be useful in the treatment of benign endometrial proliferative lesions. To avoid difficulties, endometrial proliferative lesions should be diagnosed early and treated properly.

Metformin treatment of individuals with aberrant endometrial proliferation (DPE, simple hyperplasia, and complicated hyperplasia) causes endometrial atrophy, which inhibits abnormal cell growth and, as a result, decreases perimenopausal haemorrhage.