Progestogen addition with low-dose levonorgestrel intrauterine system in menopausal hormone treatment gives less normal breast tissue proliferation than oral norethisterone acetate or medroxyprogesterone acetate

BackgroundThe impact of hormones on the development of breast cancer is despite extensive studies, incompletely understood. Combined estrogen-progestogen treatment augments the risk for breast cancer beyond that of estrogen alone, according to numerous studies. The role of breast cell proliferation as a promoter in the development and growth of breast cancer is well recognized.Materials and methodsSeventy-nine patients from three randomised trials were subject to a re-analysis of breast cell proliferation: (1) 22 women received continuous combined treatment with oral estradiol (E2) 2 mg/norethisterone acetate (NETA) 1 mg once daily for 3 months. (2) Thirty-seven women received 2 months of sequential treatment with oral conjugated equine estrogens (CEE) 0.625 mg daily combined with medroxyprogesterone acetate (MPA) 5 mg for 14/28 days of each cycle. (3) Twenty women received oral estradiol-valerate (E2V) 2 mg daily combined with levonorgestrel (LNG) intrauterine system (IUS), 20 μg/24 h for 2 months. Fine needle aspiration (FNA) (studies 1 and 3) and core needle biopsy (CNB) (study 2) were used for the assessment of breast cell proliferation.ResultsThere were no baseline proliferation differences, but at the end of treatment there was a highly significant between-group difference for E2V/LNG IUS versus the other two groups (p = 0.0025). E2/NETA and CEE treatments gave a 4–7-old increase in proliferation during treatment (p = 0.04) and (p = 0.007), respectively, which was absent in the E2V/LNG group, showing a significant correlation with insulin-like growth factor binding protein-3 (IGFBP-3) serum levels.ConclusionE2V in combination with very low serum concentrations of LNG in the IUS gives no increase in proliferation in the normal breast.

Comparison of safety and efficacy of Ormeloxifene and Norethisterone acetate in the treatment of heavy menstrual bleeding

Background: Menorrhagia (menstrual blood loss more than 80% per cycle) affects 10-33% of women at some stage of their lives. Medical management is the first line of therapy for menorrhagia (heavy menstrual bleeding: HMB). Progestins have been found to be very effective in the management of heavy menstrual bleeding especially during acute episodes, norethisterone acetate being widely used for the same. Ormeloxifene is a new drug with promising results in managing HMB. The study was undertaken to compare the efficacy, safety and acceptability of Ormeloxifene /Norethisterone acetate in the medical management of heavy menstrual bleeding.Methods: This was a retrospective study conducted from January 2016 till December 2018 in which 98 women of reproductive age group presented with abnormal uterine bleeding without any organic, systematic and iatrogenic causes. The patients were divided into 2 groups. Those wanting contraception along with control of HMB were assigned to Group O and given Ormeloxifene and others were given norethisterone (Group N). The primary outcomes measured were menstrual blood loss assessed subjectively by patients and ultrasonography for endometrial thickness. The secondary outcomes measured were acceptability and side effects of Ormeloxifene and norethisterone.Results: There is a significant reduction in menstrual blood loss as evidenced by the history of patients recorded on follow up and there was a significant reduction in the endometrial thickness as evidenced on follow up scan at the end of 3-4 months. no major side effects were observed with both the drugs.Conclusions: Ormeloxifene in comparison to norethisterone acetate with its effectiveness, significant results, convenient dosages schedule and no major side effects is an effective and safe alternative medical management of HMB.

Is the Expression of the Components of the Carotid Matrix of Rats Influenced by Estrogen, Progestin and Tibolone?

Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by real-time polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.