Mahéra Al-Akoum

Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial.

Objective: The aim of this pilot double-blind, randomized clinical trial, which initially targeted breast cancer survivors, was to obtain preliminary evidence of the effect of Hypericum perforatum extract (St. Johns wort extract) compared with placebo on symptoms and quality of life of symptomatic perimenopausal women. We also assessed practical difficulties in recruiting women to such a trial. Methods: Symptomatic perimenopausal women aged 40 to 65 years who experience hot flashes (three or more per day, Heart and Estrogen/Progestin Replacement Study scale) were randomly assigned to receive ethanolic St. Johns wort extract (900 mg TID) or placebo. The women were asked to keep a daily diary during the week before randomization and during the week before the 3-month follow-up (primary outcome) to record hot flash frequency and intensity. A hot flash score (frequency × severity) was calculated. The Menopause-Specific Quality of Life questionnaire was used to assess menopause-specific quality of life. Results: Forty-seven women were randomized. After 12 weeks of treatment, a nonsignificant difference favoring the St. Johns wort group was observed in the daily hot flash frequency (St. Johns wort, −2.3 ± 3.6; placebo, −1.0 ± 2.2; P = 0.11) and the hot flash score (−3.8 ± 8.3 and −1.8 ± 6.5, respectively; P = 0.10). After 3 months of treatment, compared with the placebo group, women in the St. Johns wort group reported significantly better menopause-specific quality of life (P = 0.01) and significantly fewer sleep problems (P = 0.05). Conclusions: Hypericum perforatum may improve quality of life in ways that are important to symptomatic perimenopausal women, but these results need to be confirmed by a larger clinical trial.

Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study.

Breast cancer cell cultures were exposed to different concentrations of black cohosh, estradiol (E2), and tamoxifen to examine the effect on cell proliferation; cytotoxicity was assessed by using sulforhodamine B (SRB) dye solution. E2 (10(-10) - 10(-8) mol/L) markedly stimulated the proliferation of MCF-7 cells (p < 0.01). Tamoxifen stimulated MCF-7 cell proliferation at 10(-6) mol/L and 10(-5) mol/L (p < 0.005) but inhibited in a dose-dependent fashion the proliferative effect of E2 (p < 0.001). Black cohosh alone did not show any stimulatory effect, but exhibited a cytotoxic effect, which was significant at 10(3) microg/mL (p < 0.001). Adding black cohosh at 10(0)-10(3) microg/mL to E2 at 10(-9) mol/L also resulted in a dose-dependent inhibition of E2 proliferative effect. Interestingly, the combination of black cohosh (10(0)-10(3) microg/mL) with increasing tamoxifen concentrations further inhibited MCF-7 cell growth. On MDA-MB-231 cells, neither E2 nor tamoxifen displayed any detectable effect. However, black cohosh inhibited MDA-MB-231 cell proliferation at 10(3) microg/mL (p < 0.05), and this inhibitory effect was enhanced by increasing tamoxifen concentrations. This study reveals a cytotoxic effect of black cohosh on both estrogen-sensitive and estrogen-insensitive breast cancer cells and a synergism with tamoxifen for inhibition of cancerous cell growth.

Promotion of angiogenesis and proliferation cytokines patterns in peritoneal fluid from women with endometriosis

Studies have long sought specific cytokines that could characterize endometriosis. Either due to variations between study designs regarding the assessment criteria for the cytokine or to low power resulting from small sample size, no factor proved to be sufficiently specific to endometriosis. In other clinical fields, a combination of several markers proved to be more powerful than a single-molecule approach. As well, in the context of endometriosis, simultaneous assessment of several cytokines present in the peritoneal fluid might help in unveiling patho-physiological processes, thus contributing to a better understanding of the condition. Therefore, the objective of this study was to investigate peritoneal fluid cytokines-derived of endometriotic women. For this retrospective case-control study, peritoneal fluid samples were obtained at laparoscopy and assessed by multiplex. Our data showed distinct patterns of peritoneal fluid cytokine concentrations in endometriotic women most notably a marked increase in EGF, FGF-2, IL-1α, MIP-1β, TGFα, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17α, MDC and Rantes. The overall effect of fertility status revealed a significant difference for only one cytokine, namely MDC. Furthermore, FLT-3L and IP-10 levels were decreased in endometriosis patients, the former in both menstrual cycle phases and the latter in the secretory phase. A significant inverse Pearson correlation (p<0.05) was noted between pro-angiogenic cytokines EGF and FGF and the anti-angiogenic cytokine IP-10 in endometriosis patients at stages III-IV and in the secretory phase. These changes may exacerbate the local peritoneal angiogenic and proliferative reaction observed in women with endometriosis, and contributes to its pathophysiology.

Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis☆

Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic inflammation, and natural specific inhibitors, including soluble IL1 receptor accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are critical for counterbalancing the pleiotropic effects of IL1. The objective of this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2 and IL1β, in the peritoneal fluid of women with and without endometriosis. Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA. sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV. sIL1R2 concentrations were decreased, and those of IL1β were significantly increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were significantly decreased in the secretory phase of the menstrual cycle, and IL1β concentrations were elevated in the proliferative and the secretory phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with endometriosis who were infertile, fertile, suffering from pelvic pain or pain-free. However, IL1β concentrations were significantly reduced in women with endometriosis who were infertile or had pelvic pain. These changes may exacerbate the local peritoneal inflammatory reaction observed in women with endometriosis and contribute to endometriosis pathophysiology and the major symptoms of this disease.

Blood soluble interleukin 1 receptor accessory protein levels are consistently low throughout the menstrual cycle of women with endometriosis

BackgroundA deficiency in the counter-regulatory mechanisms of interleukin 1 (IL1) may play a significant role in endometriosis pathogenesis and associated chronic inflammation. The aim of this study was to investigate peripheral blood levels of soluble IL1 receptor accessory protein (sIL1RAP), a potent natural inhibitor of IL1, in women with and without endometriosis.MethodsPeripheral blood samples were collected from women with endometriosis (n = 47) consulting for infertility, pelvic pain or tubal ligation, in whom the disease was diagnosed at laparoscopy. Control healthy women (n = 27) were requesting tubal ligation or reanastomosis and had no visible evidence of endometriosis at laparoscopy. sIL1RAP levels were determined by ELISA, whereas estradiol (E2) and progesterone (P4) levels were determined by competitive immunoassays.ResultssIL1RAP levels were significantly decreased in women with early endometriosis stages compared to controls (p < 0.05) and markedly during the proliferative phase of the menstrual cycle (p < 0.001). Actually, while sIL1RAP were significantly increased in the proliferative compared to the secretory phase in normal women (p < 0.0001) and peaked at the end of this phase, sIL1RAP remained consistently low and showed non-significant variations throughout the menstrual cycle in women with endometriosis.ConclusionsLower circulating levels of sIL1RAP points to a significant impairment in the counter-regulatory mechanisms of IL1, which in view of the cytokine’s potent inflammatory and growth-promoting properties may play a significant role in the pathophysiology of endometriosis.