Fa-Kung Lee

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.

Hormone therapy for patients with advanced or recurrent endometrial cancer

&NA; The “gold standard” treatment for endometrial cancer is completely staged surgery, followed by radiation or chemotherapy, based on the final pathological surgical stage and requirements. In the primary treatment of endometrial cancers, hormones are rarely taken into consideration after primary surgery. Primary treatment with hormones to preserve fertility in younger women with endometrial cancer is an attractive option, and many successful cases have been reported, although the majority of them finally received definite therapy, including total hysterectomy. The role of hormone therapy is often delayed in recurrent disease; response rates to progestins and tamoxifen or aromatase inhibitors in advanced/recurrent endometrial cancers are approximately 15–20% and nearly ≤10%, respectively. This review is focused on updated information and recent knowledge on the use of hormones in the management of women with advanced or recurrent endometrial cancers.

The benefits of estrogen or selective estrogen receptor modulator on kidney and its related disease—chronic kidney disease—mineral and bone disorder: Osteoporosis

&NA; An umbrella concept addressing the relationship between chronic kidney disease (CKD) and mineral and bone disorders has been developed in recent years. Given the high prevalence of osteoporosis‐related fractures in postmenopausal women with CKD, especially those undergoing chronic hemodialysis, the strategy used in the prevention and management of CKD and its associated osteoporosis in these postmenopausal women has become a topic of substantial debate. This controversy has ongoing relevance because osteoporosis results in a significant economic burden secondary to increased morbidity and mortality. The perfect goal of treatment and prevention includes both bone protection and renal protection, or at least protection of one disease without compromising the other disease. Both CKD and osteoporosis are frequently observed in the same patients, and often have parallel progression in postmenopausal women. Estrogen, the main female hormone during reproductive age, has been reported to have a protective effect on kidney fibrosis in several animal models, and is also considered one of the most effective drugs in the management of postmenopausal women with osteoporosis and prevention of osteoporosis. However, due to the many adverse events associated with the use of estrogen with and without progestin, some of which have contributed to significant morbidity and mortality, drug modification, which has had fewer reported incidences of adverse events without compromising the protective effect on both the kidney and bone, may have an easier road to acceptance. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone, serum lipid levels, and renal protection, without any adverse effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation trial (MORE) and its extension—Continuing Outcomes Relevant to Evista (CORE), a double‐blind, randomized clinical trial encompassing postmenopausal women with osteoporosis, showed promising results in both bone and renal studies. Raloxifene increased bone mineral density (BMD) in the spine and femoral neck and reduced the risk of vertebral fracture. In addition, raloxifene slowed the increase in the rate of serum creatinine and also significantly slowed the decrease in the estimated glomerular filtration rate; of most importance, raloxifene use was associated with significantly fewer kidney‐related adverse events. Hemodialyzed women on raloxifene treatment demonstrated increased trabecular BMD, a decrease in bone resorption markers, and a decrease in the low‐density lipoprotein‐cholesterol value. Thus, raloxifene and, most likely, other SERMs could be better in place of estrogen in the management of postmenopausal women with CKD and its associated osteoporosis, although much evidence should be provided in the advanced‐stage CKD, especially in the Stage 5 CKD patients on dialysis.

Disease activity of pregnant women with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune and multisystemic disease with a significant female predominance, particularly during the reproductive years (ratio 15:1), affecting up to one in 1000 women of child-bearing age. Pregnancy is considered a very high-risk period for women with SLE, and therefore has been strongly discouraged in those suffering from SLE for the most part until recent years. A study of 13,555 deliveries of women with SLE showed that they had a 20-fold higher risk of maternal mortality and a higher rate than pregnant women without SLE of hypertension, pregestational diabetes mellitus, renal impairment, pulmonary hypertension, major infection, and hematological complications, as well as events such as bleeding, anemia, thrombocytopenia, stroke, deep vein thrombosis, and pulmonary embolism. Therefore, the management of SLE during pregnancy remains challenging for physicians, and outcomes for both mother and baby can be less than optimal if the disease is not managed with caution. In this issue Dr. Yang has an article addressing this important topicdpregnancy outcomes of woman with SLE in a single institute in northern Taiwan. The authors studied 60 pregnancies of 55 women with SLE and found that the pregnancy outcome was strongly positively related to the remitted disease activity of the women with SLE prior to conception and during pregnancy; these women with SLE that was quiescent prior to conception and during pregnancy had a longer gestation period and a lower complication rate with pregnancy, and delivered newborns with higher body weight than those women with active SLE. Therefore, the authors emphasized the importance of requiring women with SLE to consult with obstetricians prior to conception, and to maintain remitted disease activity with the help of rheumatologists before and during pregnancy. In fact, teamwork in modern medical care has become one of the most important issues in providing better care for diseased patients and for improving the global health of the general population. We congratulate the authors on their success and also appreciate their contribution to this field. There is much evidence supporting the importance of SLE quiescence prior to conception, although multivariate analysis from Dr. Yangs report failed to identify its value. The risk of flare appears to be dependent on disease activity 6e12 months before becoming pregnant. Women without active SLE during this period have a lower risk of flare

Squamous cell carcinoma occurring in the pelvis after total hysterectomy and bilateral salpingo-oophorectomy for an ovarian mature teratoma with malignant transformation.

Department of Obstetrics and Gynecology, Cardinal Tien Hospital-Hsintien, New Taipei City, Taiwan Department of Obstetrics and Gynecology, Fu Jen Catholic University, New Taipei City, Taiwan Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan e Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan h Institute of Hospital and Health Care Administration, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan j Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan k Infection and Immunity Research Center, National Yang-Ming University, Taipei, Taiwan

Recurrent pregnancy loss and thrombophilia in women with PCOS.

In this issue Kazerooni and colleagues have authored an interesting article entitled “Correlation between thrombophilia and recurrent pregnancy loss in patients with polycystic ovary syndrome (PCOS): A comparative study”. Based on the absence or presence of recurrent pregnancy loss (RPL) and polycystic ovary syndrome (PCOS), the authors have tried to determine the association of thrombophilia and RPL in patients with and without PCOS, using a case-controlled comparative study, and separating the subjects into four groups. This study attempted to shed light on two medically challenging areas in obstetrics and gynecologydRPL and PCOSdthe etiology of both of which is still uncertain. RPL is defined by two or more failed pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology. The potential etiologic factors in the association and causation of RPL can be separated into three categories: definite, probable, and doubtful. Factors that have a definite association with RPL include parental genetics, uterine abnormalities, PCOS, antiphospholipid syndrome (APS), and factor V Leiden (FVL) mutation. Probable associations with RPL include uncontrolled thyroid disease, uncontrolled diabetes, T-helper type 1 (Th1) cell cytokine bias, increased natural killer (NK) cell cytotoxicity, and maternal human leukocyte antigen (HLA) levels. The only definite causation of RPL has been found to be parental genetics. Other causes of RPL include uterine abnormalities, uncontrolled thyroid disease, uncontrolled diabetes, PCOS, APS, FVL mutation, Th1 cytokine bias, increased NK cell cytotoxicity, and maternal HLA alleles. One of the challenges for most researchers is how to identify those limited RPL cases with genetic defects who are destined to miscarry, from other treatable ones. In addition, screening for inherited or acquired thrombophilias (especially FVL and prothrombin gene mutations, such as prothrombin G20210A gene mutations, and protein C, protein S, and antithrombin deficiencies, as noted by Kazerooni et al, might be reasonably acceptable when patients have personal history of venous thromboembolism in a nonrecurrent risk factor setting, or if there is a first-degree relative with a known or suspected high-risk thrombophilia. However, any association between hereditary thrombophilias and RPL has not been supported by two prospective cohort studies. In addition, it is acknowledged that APS is the only thrombophilia known to have a direct influence on pregnancy loss, although much

Is hysterosalpingography a good tool to confirm the patency of tubes

Hysterosalpingography (HSG) plays a crucial role in determining the anatomic causes of female subfertility and/or infertility, especially for uterine structure and tubal status abnormalities. These structural abnormalities include septum or tumor of the intrauterine cavity, adhesion or filling defect of the intrauterine cavity, and hydrosalpinx, tubal adhesion, or tubal occlusion, which may be detected by HSG examination. However, reliability of HSG is always questionable, especially for the diagnosis of tubal occlusion. Spasms of the lower genital tracts might be one of the single most factors contributing to pseudo-obstruction of tubes during HSG examination. In fact, HSG is still considered to be a relatively uncomfortable and an even painful procedure, which might be bothersome to women during examination. However, tubal occlusion, when the diagnosis is made,may result in different therapeutic choices for the affected couples. In theory, it is impossible to use less invasive and more economically assisted reproductive techniques, such as an intrauterine insemination, to facilitate these infertile couples with tubal occlusion. By contrast, a true tubal occlusion should be treatedwith recanalization either through an advanced technological method such as robotic surgery or microscopic surgery, and directly by in vitro fertilization and/or embryo transplantation, which is not required for tubal spasm. Therefore, an accurate determination of the potential causes of female infertility is required to facilitate effective treatment and avoid pitfalls related to inappropriate or delayed therapy. Subsequent confirmation of tubal problems is especially critical when assisted reproductive techniques are planned. Laparoscopy might be the optimum and thus the “gold standard” procedure for this purpose. Therefore, it is not surprising that Kahyaoglu and colleagues used diagnostic laparoscopy as a reference to evaluate the reliability and accuracy of HSG in infertile women in their study published in this issue of the Journal of the Chinese Medical Association. The study by Kahyaoglu and colleagues examined 89 infertile women who had received HSG and diagnostic laparoscopy procedures simultaneously, and found that women with diagnostic laparoscopy-confirmed tubal patency might have shorter time-period intervals between the first HSG and distal tubal filling than those with tubal occlusion (8.4 seconds vs. 12.0 seconds, p1⁄4 0.057). Based on the absence of statistical significance, the authors concluded that it remained uncertain as to the value necessary to detect the clinically

Hyperemesis gravidarum, pregnancy and bone loss

It has been considerable controversy over the past decades as to whether high parity and/or prolonged lactation periods are detrimental to bone mineral density (BMD). Concerns exist regarding a loss of BMD during pregnancy (at the lumbar spine of 7.6% relative to age-matched nonpostpartum controls), although it may be transient, contributing to the consideration of the importance of adequate nutrition support for the pregnant women, including essential amino acids, trace mineral elements, and calcium or vitamin D supplementation. A recent prospective randomized study was conducted to examine associations of several aspects of parity and history of lactation with incident hip fractures and clinical fractures and, in a sunset of women with BMD, and the results showed no correlation between patterns of parity or history of lactation and fracture risk or BMD. Although it is negative, the risk of inadequate nutritional support is still high in pregnant women. Many pregnant women suffer from nausea and vomiting in their first trimester. Among these women, a small fraction may result in the most severe form, hyperemesis gravidarum, characterized by persistent vomiting, weight loss of more than 5%, ketouria, electrolyte abnormality and dehydration. In theory, it might further worsen the nutrition deficiency in these pregnant women. We are glad to learn that Dr. Uysals study focused on this topic. The authors published an article in the current issue of the Journal of the Chinese Medical Association to investigate the relationship between bone loss and hyperemesis gravidarum. The authors compared BMD and some laboratory parameters of pregnant women with (n 1⁄4 40) and without (n 1⁄4 39) hyperemesis gravidarum in Kayseri Education and Research Hospital between June and December 2015. The authors found no significantly statistical difference of dual energy xray absorptiometry (DEXA) and laboratory parameters between women with and without hyperemesis gravidarum. They concluded that pregnancy with hyperemesis gravidarum is not increasing risk of bone loss compared with that without is. The current study is interesting and worthy of a further discussion. First, this study, by accident, found that vitamin supplementation seemed to be beneficial for early-pregnancy women. The authors found pregnant women without

Plant products impairing fertility of animals

Fertility is possibly the most important capability contained within living cells or species. Therefore, finding the most efficacious way to enhance or promote fertility is the main goal of all living things. To best manage natures strong predisposition for fertility, plant-based traditional medicines for birth control have long been incorporated into medical practices throughout the world, including those in the rural populations of North-East India, China, and Africa. In this issue of the Journal of the Chinese Medical Association, Muhammad and Muhammad published a very interesting review article entitled “Anti-fertility activity of medicinal plants,” introducing >60 species of plants that might possess antifertility activity. This article divided these antifertility plants into five categories, namely, plants exhibiting antiovulation activity, anti-implantation activity, antispermatogenic activity, antifertility activity by interfering with the action of hormones, and finally abortifacient activity. The authors claimed to have provided a comprehensive summary of medicinal plants from the literature, including results from Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed searches using terms such as antifertility, anti-implantation, antiovulation, and antispermatogenic activity of plants. We applaud the authors on the success of this article, because their research and information-gathering task were not easy. However, given the size of the project that they undertook, it goes without saying that their review ultimately will omit certain important data. For example, information about the extract of Drynaria quercifolia (L.) J. Smith rhizome was missed in their review. This extract was proven to possess significant antifertility activity, not only showing a high efficacy for both abortifacient and anti-implantation activities, but also affecting sexhormone release. In addition, the presence of an “adjuvant reagent,” including that in solutions or solvents, could influence the final effect of antifertility activity of these medicinal plants. As noted earlier, the methanol extract of D. quercifolia (L.) J. Smith rhizome has shown higher efficacy for both abortifacient ( p < 0.01) and anti-implantation performance ( p < 0.01) than its aqueous extract dose. Furthermore, the effect of plant-derived products on antifertility may be dose dependent, reversible, and sex dependent. For example, Shaik and colleagues demonstrated the antifertility potential of methanolic leaf extract of Artemisia vulgaris, which showed a strong and significant decrease in implant formation