99mTc labeled genistein kits: development methods and quality control for breast cancer radiotracer applications

Objective. Selective estrogen receptor modulators (SERMs) have been widely used to treat breast cancer, osteoporosis, and postmenopausal symptoms. SERMs have an affinity for estrogen receptors (ER) in target tissues and resist stimulation of the breast, bone, and endometrium. Genistein as an isoflavone compound that has a high affinity for ERβ targets makes it a potential target or prognostic marker for breast cancer. This study was carried out to develop 99mTc-genistein kit that can be used to detect breast cancer. Methods. The synthesis process and quality control were investigated to obtain the optimal formula for the ratio of a substance, reducing agent, optimal conditions of the synthesis reaction, physicochemical properties of the kit, and its stability to meet the requirements of radiochemical purity. Results. The radiochemical purity in the development of the radiopharmaceutical kit was 93.25% ± 0.30%. The physicochemical properties of the kit preparations showed hydrophilic properties, good plasma protein binding, no electrical charge, and were stable at storage temperatures. Conclusions. The radiochemical purity of the radiopharmaceutical kits meets the requirements of the United State Pharmacopeia and has good physicochemical properties to be developed into kits.

Probiotics and Isoflavones as a Promising Therapeutic for Calcium Status and Bone Health: A Narrative Review

Probiotics have potential clinical effects for treating and preventing osteoporosis. Meanwhile, isoflavones have attracted much attention due to their ability to prevent postmenopausal symptoms. Research has established that probiotics and isoflavones can regulate hormones, immune cells, and the gastrointestinal system, acting as links in the gut–bone axis. However, combining the effects of probiotics and isoflavones on calcium status and bone health is a more novel and a still-evolving research area. Lactobacillus and Bifidobacterium are the foremost strains that influence bone health to a significant extent. Among the isoflavones, daidzein, genistein, and the metabolites of genistein (such as equol) stimulate bone formation. It can be concluded that probiotics and isoflavones promote bone health by regulating calcium uptake, gut microbiota, and various metabolic pathways that are associated with osteoblast activity and bone formation. Nevertheless, further experiments of probiotics and isoflavones are still necessary to confirm the association between calcium bioavailability and bone health.

Evaluation of quality of life and postmenopausal symptoms of postsmenopausal women – a prospective observational study

Background: Menopause is a phase of transformation from the reproductive to the non-reproductive period in a woman’s life. In the aging population it is nature’s defensive event against reproductive morbidity and mortality.“An individual’s insight of their position in conditions such as the value and culture systems in which they survive and in relation to their goals, expectations, standards and concerns” in life is defined as QOL. A negative effect on the common health and quality of life (QOL) as well as the contentment of middle-aged women may occur due to Menopause and associated biologicals. Objective: To evaluate the quality of life and postmenopausal symptoms in postmenopausal women. Methods: In this present study 100 patients were recruited and studied for their demographic details and their postmenopausal qualityof life related aspects. The obtained data was analysed using the SPSS software. Results: The mean menopausal age was found to be 45.6 years. The maximum and minimum menopausal ages were 37 and 60 respectively in this study. On analysis, MSQOL revealed that 89% women suffered sexual symptoms, followed by 78% women who suffered physical symptoms like decrease in physical strength and stamina, aches in back of neck and head, aching muscles and joints. Approximately half of the women experienced vasomotor and psychological symptoms. UQOL revealed lower or poor QOL of the postmenopausal women. The overall average scores for occupational, health, emotional, sexual and total QOL for 100 participants was found to be 11.37, 21.03, 17.84, 3.67 and 53.34 respectively

Estrogenic and Antioxidant Activities of Pterocarpus soyauxii (Fabaceae) Heartwood Aqueous Extract in Bilateral Oophorectomized Wistar Rat

Phytoestrogens are used to ease postmenopausal symptoms, a property probably due to estrogenic and antioxidant effects. Pterocarpus soyauxii (P. soyauxii) is empirically used in Cameroon to treat among others primary and secondary amenorrhea. The aim of this study is to evaluate estrogenic and antioxidant activities of P. soyauxii heartwood aqueous extract in bilateral oophorectomized Wistar rats. Firstly, a characterization of the extract was carried out. For that, flavonoids, phenols, and tannins levels in P. soyauxii extract were evaluated by colorimetric assays and UHPLC-MS analysis was realized. In vitro antioxidant analysis of P. soyauxii was conducted using DPPH, ABTS, and FRAP assays. Secondly, 2 sets of pharmacologic tests were carried out. The results revealed that P. soyauxii aqueous extract contains, respectively, 229.42 ± 3.62 mg EAG/g, 63.42 ± 2.16 mg EQ/g, and 27.88 ± 0.23 mg ETA/g of polyphenols, flavonoids, and tannins. UHPLC-MS enabled identifying seven components including mono(2-ethylhexyl) phthalate, cembrene, 3′,5′-dimethoxy-4-stilbenol, and linoleic acid. DPPH, ABTS, and FRAP assays revealed that P. soyauxii extract possessed a high antioxidant activity with IC50 value of 730.20 µg/mL, 892.90 µg/mL, and 765.75 mEAG/g of extract, respectively. In the uterotrophic assay, P. soyauxii extract induced significant increase of fresh uterine weight, uterine and vaginal epithelial size, and mammary glands differentiation compared to Ovx control. In the postmenopausal model, compared to the sham control, vagina and uterine dystrophies were observed in Ovx rats treated with distilled water. P. soyauxii aqueous extract expressed estrogenic-like effects on vagina and did not affect uterine epithelial height compared with vehicle groups. On the back of these vaginotrophic effects, the extract displayed antiatherogenic properties by reducing ( p < 0.001) AI and LDL cholesterol level as compared to Ovx control group. The extract at 200 mg/kg significantly prevented the increase of MDA ( p < 0.01) level and decreased nitrites ( p < 0.001) and GSH ( p < 0.01) levels compared to Ovx rats. These beneficial effects are related at least in part to the presence of compound such as mono(2-ethylhexyl) phthalate, 3′,5′-dimethoxy-4-stilbenol, and linoleic acid. Overall, P. soyauxii aqueous extract exhibits estrogenic and antioxidant effects which can inhibit postmenopausal symptoms by providing vaginal stratification, improving lipid profile and insulin sensitivity, and reducing oxidative stress without side effects on the endometrium and mammary gland in 84-day Ovx rats.

Therapeutic Application of Saffron for Improvement of Women’s Health: A Review of Literature

Saffron or crocus sativus L. (C. sativus) has been widely used as a food additive as well as a therapeutic agent in traditional medicine for centuries, especially in Asian countries. This spice consists of three bioactive components, including picrocrocin, safranal, and crocin, which exert alleviating effects in a wide range of disorders (e.g.cardiovascular, respiratory, gastrointestinal, neurodegenerative, psychiatric and female-specific disorders). Anti-nociceptive, anti-inflammatory, and anti-oxidative characteristics were reported for this herbal agent. Additionally, several studies have addressed the potential role of saffron in modulating the serotonergic system, which could be helpful in treatment of some diseases specific to women such as Premenstrual Syndrome (PMS), Postpartum Depression (PPD), postmenopausal symptoms, and sexual dysfunction. Nowadays, use of herbal medicine instead of chemical prescriptions has become very popular due to their generally lesser side effects and cultural acceptability. In the present report, we provided an overview of the current literature regarding the potential effects of saffron on women’s health. Taken together, saffron seems a spice with strong beneficial impacts on various aspects that a woman might challenge with. Further trials could pave the way for the introduction of saffron as a routine safe treatment of aforementioned conditions in women population.

Therapeutic Potential of Isoflavones with an Emphasis on Daidzein

Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.

Ameliorative Effects of Pueraria lobata Extract on Postmenopausal Symptoms through Promoting Estrogenic Activity and Bone Markers in Ovariectomized Rats

Pueraria lobata (Willd.) Ohwi, known as kudzu, is one of the most popular traditional medicines in Asian countries. It has been widely used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms. This study aimed to investigate the estrogenic effect of P. lobata extract (PE) against postmenopausal osteoporosis in ovariectomized (OVX) rats. OVX rats were treated with PE (25–1600 mg/kg) for 8 weeks. Biochemical parameters, estradiol, and bone turnover markers (e.g., osteocalcin, C-terminal telopeptide fragment of type I collagen, deoxypyridinoline, and pyridinoline) were measured in plasma samples. In addition, estrogen receptor-alpha (ER-α) protein expression and morphology of uterine were evaluated. Long-term treatment with PE did not cause liver damage in OVX rats. PE supplementation reduced body weight gain in obese rats with high lipid accumulation induced by ovariectomy. Furthermore, PE exhibited a protective effect against insulin resistance, hyperlipidemia, and hepatic lipid peroxidation. PE treatment increased uterine weight and thickness of the uterine layers in cases of uterus atrophy due to removal of ovaries. The levels of bone turnover markers, which were significantly increased in OVX rats, were decreased by PE treatment. Western blotting analysis showed that ER-α protein expression was upregulated in PE-treated rats compared with OVX rats. These results suggest that PE could be a promising alternative functional food for improving menopausal symptoms.

Effectiveness of tibolone in the management of postmenopausal symptoms

Background: Tibolone is a synthetic hormone relplacemert therpy prepration with estrogenic, progestogenic and androgenic tissue selective mechanism of action. It has advantages over traditional preparations of estrogen and progesterone considering the risks and adverse effects. Objective: To evaluate the extent of effectiveness and adverse effects of Tibolone. Method: This clinical trial was done in Khulna Medical College Hospital between January to December 2019. Postmenopusal women were selected by inclusion and exclusion criteria. Alternate participant was included in two different group. Participants of group A was treated with Tibolone for 6 months and participants of group B was treated with placebo for 6 months. Each participant was followed up after 3 and 6 months. Four categories of postmenopausal symptoms (hot flushes, night sweats, sleep disturbance and mood swinging) were evaluated. Participants were monitored for any adverse effects. Severity of postmenopausal symptoms was measured by using menopausal visual analogue scale. Results: Total 90 partcipants, were enrolled in this study, half of them were included in each group. Baseline assessment in group A participants revealed mild, moderate and severe symptoms in 05 (12%), 29 (64%) and 11 (24%) women respectively. After 6 months of treatment with tibolone, 35 (78%) participants became asymptomatic. This improvement is statistically significant (p<0.001). In group B, participant's baseline assessment revealed mild, moderate and severe symptoms in 07 (16%), 28 (62%) and 10 (22%) cases respectively. After 6 months of treatment with placebo, 02 (05%) women were asymptomatic. This improvement is not statistically significant. No adverse event was observed during treatment with tibolone. Comparison between the tibolone and placebo treatment group showed, tibolone treatment is better. Conclusion: Tibolone effectively relieves the postmenopausal symptoms and improves the quality of women's health at menopause. Bang Med J Khulna 2020: 53 : 31-34

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence

Menopause, probably the most important natural change in a woman’s life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1β, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.