Kuan-Hao Tsui

Hormone therapy for younger patients with endometrial cancer.

The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.

Effects of dehydroepiandrosterone supplementation on women with poor ovarian response: A preliminary report and review.

OBJECTIVE To investigate the effect of dehydroepiandrosterone (DHEA) supplementation on women with poor ovarian response (POR). MATERIALS AND METHODS Women with POR treated with flexible daily gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles at The Reproductive Center in Kaohsiung Veterans General Hospital between January 2013 and October 2013, were enrolled for this prospective study. When patients failed to become pregnant during the first IVF cycle, they were treated with DHEA supplementation (30 mg, 3 times a day, orally) for 3 months (mean 12.2 weeks) before the next IVF cycle. Parameters of biochemical, ultrasound and treatment outcomes were compared before and after DHEA supplementation. RESULTS Ten patients with a mean age of 36.6 ± 4.2 years were identified. After DHEA treatment, there was a significant increase in antral follicle count, from 2.8 ± 1.0 to 4.1 ± 1.2 (p < 0.05), and anti-Müllerian hormone, from 0.4 ± 0.2 ng/mL to 0.84 ± 0.2 ng/mL (p < 0.001). A significant decrease of Day 3 follicle-stimulating hormone and estradiol, from 14.4 ± 1.7 mIU/mL to 10.1 ± 0.7 mIU/mL and from 51.2 ± 6.3 pg/mL to 35.2 ± 4.2 pg/mL, respectively (both p < 0.001), was noted. Increased numbers of retrieved oocytes (from 2.4 ± 1.1 to 4.2 ± 1.2; p < 0.01), fertilized oocytes (from 1.7 ± 0.5 to 3.8 ± 1.1; p < 0.001), Day 3 embryos (from 1.7 ± 0.5 to 3.7 ± 1.1; p < 0.001) and transferred embryos (from 1.7 ± 0.8 to 2.8 ± 0.8; p < 0.01) were also seen in these women with POR after DHEA treatment. Three women became pregnant after DHEA treatment. CONCLUSION The potential benefits of DHEA supplementation in women with POR were suggested by the biochemical parameters and IVF outcomes.

Non-classical estrogen receptors action on human dermal fibroblasts.

OBJECTIVE To study the possible non-genomic effect of selective estrogen receptor modulators on human dermal fibroblasts (HDF). MATERIALS AND METHODS WS1 cells were used to test the effect of raloxifene. The mRNA expressions of estrogen receptor (ER) α and β and G protein-coupled ER 1(GRP30) were examined by reverse transcription polymerase chain reaction. Apoptosis was identified by TUNEL assay and FACS analysis. MAPK and PI3 K/Akt pathways were determined by immunoblotting analysis. RESULTS Neither ERα nor ERβ, but GPR30 was detected in WS1 cells. Raloxifene increased apoptosis, which was blocked by pertussis toxin, an inhibitor of G protein, or by LY294002. Phosphorylated p38 MAPK and Akt were also increased after raloxifene treatment. CONCLUSION SERMs could induce apoptosis of HDF through G protein and PI3 K/Akt signaling, which may help understand the role of SERMs on the skin.

Roles of Estrogen and Progesterone in Endometrial Hemodynamics and Vascular Endothelial Growth Factor Production

Background: The endometrium becomes receptive to the embryo after sequential actions of estrogen and progesterone. The purpose of this study was to examine the effects of estrogen and progesterone on endometrial hemodynamics and on secretion of vascular endothelial growth factor (VEGF) from endometrial epithelial cells (EEC). Methods: Six early postmenopausal women taking sequential estrogen and progestin [days 1–11: estradiol valerate (estrogen) 2 mg daily; days 12–21: estradiol valerate 2 mg plus norethisterone acetate (progestin) 1 mg daily] were recruited. Three‐dimensional power Doppler angiography (3D‐PDA) was performed before hormone treatment (phase 0), on days 10–11 of hormone treatment (phase E), and on days 18–20 of hormone treatment (phase E + P). Ishikawa EEC were treated with or without 17‐β‐estradiol and progesterone for 24 hours, followed by determination of VEGF concentrations in the supernatants. Results: The endometrial volume was significantly increased in phase E and phase E + P as compared with that in phase 0. The vascularization index, flow index, and vascularization flow index in the subendometrial region, as measured by 3D‐PDA, were significantly higher in phase E + P than in phase 0, but there were no significant differences in these indices between phase 0 and phase E. While treatment of EEC with 17‐β‐estradiol had little enhancing effect on VEGF production, progesterone alone or in combination with 17‐β‐estradiol significantly increased VEGF secretion from EEC. Conclusion: Our data suggested that progesterone could stimulate VEGF secretion from EEC and subsequently increase subendometrial vascularity and blood flow.

Double-balloon cervical ripening catheter works well as an intrauterine balloon tamponade in post-abortion massive hemorrhage

OBJECTIVE Clinical experience in the management of post-abortion hemorrhage is limited. CASE REPORTS Two women with severe post-abortion hemorrhage were reported. One case occurred after methotrexate treatment of Cesarean scar pregnancy and the other occurred after abortion surgery. Both patients were successfully treated with a double-balloon cervical ripening catheter inducing intrauterine balloon tamponade. CONCLUSION Use of a double-balloon cervical ripening catheter either before or after systemic methotrexate treatment is one of the choices in the management of severe post-abortion hemorrhage and can prevent the use of more invasive and/or destructive procedures.

Comprehensive treatment for infertile women with severe Asherman syndrome

OBJECTIVE Many preoperative, intraoperative, and postoperative methods have been described that improve the outcomes of women with severe Asherman syndrome, and it is likely that an integrated application of all of these methods may provide better reproductive outcomes; however, there is as yet no report on this type of integrated approach. MATERIALS AND METHODS The cases of four infertile women with severe Asherman syndrome were analyzed retrospectively. The comprehensive therapeutic plan for the four women included (1) preoperative office hysteroscopy to confirm the diagnosis and evaluate the severity of disease; (2) the use of ultrasound-guided intraoperative abdominal procedures during the surgical procedure, including hysteroscopic adhesiolysis to ensure the entire the hysteroscopic dissection, and placement of a Hyalobarrier(®) gel and an intrauterine balloon catheter at the end of the surgery; (3) postoperative oral estrogen supplementation to enhance endometrial proliferation, removal of the balloon catheter, and a second-look office hysteroscopy; and (4) in vitro fertilization and embryo transfer (IVF & ET) for three of the four patients. RESULT After treatment, the endometrium was significantly thicker than at baseline (median endometrial thickness, 7.5 mm versus 3.0 mm, p < 0.05). All the women (100%, 4/4) conceived successfully (three undergoing IVF & ET, and one had a spontaneous pregnancy), but only two patients had a term pregnancy with cesarean section (one placenta previa and the other placental abruption), contributing to 50% of successful term pregnancies. One patient had the complication of abortion after amniocentesis. The last one woman underwent an abortion because of thyroid problems. CONCLUSION Comprehensive management offers promising reproductive outcomes for infertile women with severe Asherman syndrome.

Clinical application of dehydroepiandrosterone in reproduction: A review of the evidence.

Abstract The effect of dehydroepiandrosterone (DHEA) therapy on improvement of reproduction outcome is uncertain. Many earlier studies have shown conflicting results. Therefore, a review of the literature is needed to explore the role of DHEA in reproduction. We conducted a literature search of MEDLINE (Ovid) and Pub‐Med (2000–June 2014) for all relevant articles that included the terms “dehydroepiandrosterone,” “DHEA,” and “in vitro fertilization.” Among the search‐identified articles, seven prospective self‐controlled studies and four retrospective case–control studies showed DHEA as an adjuvant therapy able to improve in vitro fertilization outcomes in poor responders (women with diminished ovarian reserve and/or poor ovarian response). However, four randomized controlled trials did not support the benefit of DHEA therapy for poor responders. By contrast, one prospective randomized study showed that DHEA might be beneficial to reproduction in women without diminished ovarian reserve (normal responders). In summary, a review of the previously published studies does not provide clear evidence that DHEA can be a useful treatment to improve ovarian function in poor responders.

Lactobacillus and health

Evidence shows that Lactobacillus species are the dominant vaginal bacteria in a majority of women, contributing to an acidic environment (pH 3.5e4.5) in the vaginal area. Lactobacillus also contributes to the production of hydrogen peroxide to inhibit overgrowth of other pathogens, including group B streptococci, Escherichia coli, Staphyococcus aureus, Gardnerella vaginalis, or other fastidious or uncultivated anaerobes. Lactic acid, through the production of Lactobacillus species, is a potent and broad-spectrum bactericide and virucide. Therefore, many interventional efforts have been and are being made to restore vaginal health through the application of oral or vaginal probiotic formulations of Lactobacillus species. In addition, the benefits of restoring vaginal microbiomes in women are not only related to the health status of women themselves but also to obstetric outcomes when these women get pregnant. Therefore, management, manipulation, and restoration of a robust vaginal microbiota might be advantageous in vastly improving womens health and disease prevention. This is because historically, the presence of Lactobacillus species has been thought to be the sine qua non of healthy vaginal microbial communities in women during the reproductive age, and it might also be useful in the prevention of the benign or malignant lower genital tract diseases, such as bacterial vaginosis, sexually transmitted disease, and possible neoplasms, such as cervical intraepithelial neoplasm or cervical cancers. However, a scientific level understanding of how the vaginal microbiota is associated with obstetric, gynecological, and reproductive health remains problematic and deficient. Furthermore, a big gap in the development of effective preventive approaches to improved womens health is that the normal distribution of Lactobacillus species within the healthy vagina of women, especially in the different geographic areas, is still uncertain. Actually, the detailed information about the Lactobacillus species in the vagina of healthy women in different geographic areas might be one of the critical steps. Therefore, it is acknowledged that all new information addressing this topic should be thoroughly reviewed. The study by Mousavi et al in this issue of the Journal of the Chinese Medical Association focused on this issue to isolate and identify the Lactobacillus species in the vagina of healthy Iranian women who live in the Ahvaz area. The

Luteal phase support with gonadotropin-releasing hormone agonist.

Kung et al authored a valuable article entitled “Luteal phase support with decapeptyl improves pregnancy outcomes in ICSI with basal FSH >8 mIU/mL or mature oocytes 3”. This retrospective study enrolled 240 patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and forty-seven patients were in the decapeptyl group and 93 patients were in the control group. The authors investigated the effect of decapeptyl as an additional luteal phase support (LPS) in in vitro fertilization (IVF) cycles and tested which subgroup would benefit from the treatment. We recognize the probity of this publication. Luteal phase defect is a common problem encountered during IVF cycles. In the past, several theories have been proposed such as (1) defective corpora lutea formed from the remnants of the aspirated follicles and (2) prolonged pituitary downregulation by the gonadotropin-releasing hormone (GnRH) agonist. Both of these theories attempt to explain premature luteolysis during IVF cycles; however, there has been a lack of subsequently published studies with sufficiently reliable evidence to support these theories. By contrast, a new hypothesis of multiple corpora lutea has been proposed. This hypothesis is based on the effect occurring after ovarian hyperstimulation wherein more steroids are subsequently produced, which suggests that the negative feedback on the pituitary gland inhibits luteinizing hormone release. Premature luteolysis arise from the negative feedback by high concentrations of steroids caused by multiple corpora lutea. However, there is no doubt that LPS is essential to enhance reproductive outcomes in IVF cycles. Progesterone and human chorionic gonadotropin have served as popular and effective LPS agents. In addition, Tesarik et al described using a GnRH agonist as LPS to improve the implantation rate, pregnancy rate, and live birth rate. Several studies subsequently support the results obtained by Tesarik et al, whereas other studies show dissimilar conclusions. Taken together, two systemic reviews, which include meta-analyses, demonstrate that administering a luteal phase single-dose GnRH agonist can significantly ameliorate IVF outcomes. Kung et al confirmed in their study the beneficial effect of luteal phase single-dose decapeptyl administration on the implantation rate (24.5% vs. 17.0%; p 1⁄4 0.023), clinical pregnancy rate (49.0% vs. 33.3%; p 1⁄4 0.023), and live birth rate (41.5% vs. 28.0%; p 1⁄4 0.039). The precise mechanism of how a GnRH agonist exerts its effect in the luteal phase remains unclear. Some studies

Estrogen Effects on Wound Healing

Wound healing is a physiological process, involving three successive and overlapping phases—hemostasis/inflammation, proliferation, and remodeling—to maintain the integrity of skin after trauma, either by accident or by procedure. Any disruption or unbalanced distribution of these processes might result in abnormal wound healing. Many molecular and clinical data support the effects of estrogen on normal skin homeostasis and wound healing. Estrogen deficiency, for example in postmenopausal women, is detrimental to wound healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment may reverse these effects. Understanding the role of estrogen on skin might provide further opportunities to develop estrogen-related therapy for assistance in wound healing.