Association between the Change in Blood Pressure during Normotensive Pregnancy and the Development of Hypertension in Later Life.

Introduction: Women who experience maternal complications, including pre-eclampsia, have a higher risk of cardiovascular disease development. Although the mechanism remains unclear, there is a hypothesis that pregnancy would be a stress test for cardiovascular disease. This study aimed to investigate whether changes in blood pressure during pregnancy would be associated with developing hypertension, which is a main risk of cardiovascular disease. Methods: We conducted a retrospective study by collecting Maternity Health Record Books from 735 middle-aged women. Of these, 520 women were selected based on our criteria. 138 were defined as the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of >140/90 mmHg at the survey. The rest 382 were defined as the normotensive group. We compared the blood pressures of the hypertensive group with those of the normotensive group during pregnancy and postpartum. Then, 520 women were divided into quartiles (Q1-Q4) according to their blood pressures during pregnancy. After the changes in blood pressure for each gestational month relative to nonpregnant measurements were calculated, the changes in blood pressure were compared among the four groups. Additionally, the rate of developing hypertension was evaluated among the four groups. Results: The average age of the participants was 54.8 years (range: 40-85 years) at the time of the study and 25.9 years (range: 18-44 years) at delivery. There were significant differences in blood pressure during pregnancy between the hypertensive group and the normotensive group. Meanwhile, these two groups did not indicate any differences in blood pressure in postpartum. Higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. The rate of development of hypertension in each group of systolic blood pressure was 15.9% (Q1), 24.6% (Q2), 29.7% (Q3), and 29.7% (Q4). The rate of development of hypertension in each group of diastolic blood pressure (DBP) was 18.8% (Q1), 24.6% (Q2), 22.5% (Q3), and 34.1% (Q4). Conclusions: Changes in blood pressure during pregnancy are small in women who have a higher risk of hypertension. Levels of blood pressure during pregnancy may be reflected in individual stiffness of blood vessels by the burden of pregnancy. If so, levels of blood pressure would be used to facilitate highly cost-effective screening and interventions for women with a high risk of cardiovascular diseases.

Low Birth Weight and Prematurity Are Associated with Hypertensive Disorder of Pregnancy in Later Life: A Cross-Sectional Study in Japan.

OBJECTIVE: We previously reported that hypertensive disorder of pregnancy (HDP) was a risk factor for hypertension and hypercholesterolemia in later life. Additionally, the age-adjusted odds ratio (OR) of HDP was 2.72 for Japanese women whose mothers had a history of HDP versus those whose mothers did not. This study aimed to clarify the association of HDP with birth weight and gestational age. STUDY DESIGN: A self-administered baseline survey of the Japanese Nurses' Health Study (JNHS) cohort was conducted from 2001 to 2007. Data on 17,278 parous female nurses who knew their own birth weights were extracted from the JNHS baseline survey (n = 49,927) and subjected to cross-sectional, retrospective analysis. Data on weeks of gestation, birth weight, and history of HDP were collected. RESULTS: The age-adjusted ORs for HDP were 1.62 (95% confidence interval [CI]: 1.20-2.19) for birth weight <2,000 g, 1.24 (CI: 1.04-1.48) for 2,000 to 2,499 g, 1.11 (CI: 1.00-1.23) for 2,500 to 2,999 g, and 1.08 (CI: 0.94-1.24) for ≥3,500 g compared with 3,000 to 3,499 g. The age-adjusted ORs for HDP were 1.27 (95% CI: 1.04-1.54) for a gestational age < 37 weeks and 0.93 (0.70-1.23) for ≥42 weeks compared with 37-41 weeks. The age-adjusted OR of the birth weight score for HDP in later life was 0.98 (CI: 0.94-1.03; Cochran-Armitage trend test: z = 0.401, p = 0.688). CONCLUSION: Among women in Japan, a history of low birth weight and prematurity are risk factors for HDP in later life. The risk of HDP among women born with low birth weight and/or premature deserves attention.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies.

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events. Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years. Conclusions and Relevance: Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

OBJECTIVE: Kampo medicine, a traditional Japanese medicine, is widely used in Japan, especially in the field of menopause medicine. However, few studies have shown evidence-based effects. This study aimed to confirm the effects of kamishoyosan on menopausal symptoms with a randomized, placebo-controlled, double-blind clinical trial. METHODS: Subjects were randomly allocated to groups that received either kamishoyosan (n = 101) or a placebo resembling kamishoyosan (n = 104). The primary outcomes were the change in the number of hot flashes, depression scores, improvements of anxiety, quality of life (QOL), and menopausal symptoms before and 4 and 8 weeks after initiation of treatment with the study drug. The secondary outcome was drug safety. RESULTS: After 8 weeks, the number of hot flashes decreased after treatment in both groups, but there was no significant difference between the two groups. The changes in SDS scores showed the same results. Moreover, no significant differences were observed between the two groups in assessments with the STAI, SF-36, and JSOG menopausal index. No serious adverse effect was reported. CONCLUSIONS: This first placebo-controlled double-blind randomized trial with kamishoyosan demonstrated that it was safe and had some effects on climacteric symptoms, but not significant compared with placebo. Some problems, such as placebo effects, in the study of Kampo therapy for menopausal symptoms, were revealed. This trial is registered with the trial registration number. UMIN 000006042.

Spontaneous unscarred uterine rupture and surgical repair at 11 weeks of gestation in a twin pregnancy.

A uterine rupture may result in a massive hemoperitoneum, which can be fatal to both the fetus and mother. Most uterine ruptures during pregnancy occur within a scarred uterus, rarely occurring in an unscarred uterus. Here, we report a very rare case of spontaneous rupture in an unscarred uterus at 11 weeks of gestation of a twin pregnancy and its surgical repair. A 37-year-old nulliparous infertile woman became pregnant with twins after artificial insemination and gonadotropin therapy. She underwent emergency surgery at 11 weeks of gestation due to an acute abdomen caused by massive hemoperitoneum. Upon laparotomy, one fetus with placenta was extruded into the abdominal cavity through a 3-cm myometrium rupture on the left posterior wall of the uterus. After surgical repair of the rupture site, the remaining fetus was alive and was successfully delivered by cesarean section at 34 weeks of gestation.

Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses.

STUDY QUESTION: Is there any relationship between vitamin D [25 (OH) vitamin D], total plasma homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in women with recurrent pregnancy losses (RPL)? SUMMARY ANSWER: Women with MTHFR 677TT (homozygous mutation, TT) genotype have significantly lower vitamin D levels, higher homocysteine and natural killer (NK) cell cytotoxicities than those of women with MTHFR 677CC (wild type, CC) and 677CT (heterozygous mutation, CT) genotypes. WHAT IS KNOWN ALREADY: Vitamin D insufficiency, MTHFR C677T polymorphism and hyperhomocysteinemia have been reported as risk factors for RPL. However, the relationship between these risk factors is not known in this population. STUDY DESIGN, SIZE, DURATION: This is a retrospective cross-sectional study, including 837 women with RPL, who were enrolled in Reproductive Medicine and Immunology, Chicago Medical School, between 2012 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with two or more RPL prior to 20 weeks of gestation were included. To investigate whether the MTHFR C677T polymorphism affects the levels of homocysteine and vitamin D as well as immune parameters in women with RPL, biochemical data, such as plasma total homocysteine and serum vitamin D levels, and immune parameters, including NK cell cytotoxicity, were analyzed by MTHFR C677T genotype (CC, CT and TT). MAIN RESULTS AND THE ROLE OF CHANCE: The serum level of vitamin D in TT was significantly lower when compared with those of CT (P = 0.001) and CC (P = 0.003), while the level of homocysteine in TT was significantly higher than those in CT (P = 0.01) and CC (P = 0.01). NK cytotoxicity in TT was significantly higher than that of CC (P = 0.04) but not CT (P = 0.09). There was a significant negative correlation between the levels of vitamin D and homocysteine in TT (r = -0.357, P < 0.01). In multivariate analysis, vitamin D insufficiency (<30 ng/ml) was an independent risk factor for hyperhomocysteinemia (adjusted odds ratio 1.89, 95% CI 1.41-2.52). LIMITATIONS, REASONS FOR CAUTION: The study was retrospective and included only women with RPL but not healthy fertile controls. In addition, folic acid, vitamin B6 and B12 intake, which could modify the level of homocysteine and vitamin D, were not investigated. Thus, a considerable part of women might have folic acid and vitamin D supplementation and prenatal vitamin pills, and there are probable confounders in this study associated with unrestricted vitamin supplementation. Therefore, the findings should be carefully interpreted and applied to RPL women with MTHFR gene polymorphism. WIDER IMPLICATIONS OF THE FINDINGS: The findings attained in this analysis regarding the MTHFR polymorphism and its relationship with vitamin D, homocysteine and NK cytotoxicity may aid in uncovering the underlying etiology and mechanism for RPL. The study highlights an interplay between nutrition and immune responses in RPL. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. None of the authors have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Malignant transformation arising from mature cystic teratoma of the ovary presenting as ovarian torsion: a case report and literature review.

OBJECTIVE: Ovarian torsion is an acute gynecological condition. Torsion is more likely to occur with benign rather than malignant tumors. Mature cystic teratoma of the ovary (MCTO) is frequent in women of reproductive age; however, the incidence of malignant transformation is approximately 2%. We report a case of malignant transformation of MCTO presenting as ovarian tumor torsion. CASE REPORT: A 51-year-old premenopausal woman was diagnosed with mature cystic teratoma in the left ovary 7 years ago. The patient visited our hospital because she had been experiencing of pain in left lower abdomen for the past two days. She was diagnosed with ovarian tumor torsion and underwent emergency surgery. The left ovarian tumor was twisted, and left salpingo-oophorectomy was performed. Histopathological examination revealed squamous cell carcinoma arising from the MCTO. We carefully followed the patients without performing staging laparotomy. On postoperative day 112, multiple lymph node metastases in the pelvic and para-aortic areas were found by positron-emission tomography and computed tomography. After referral to a university hospital, total hysterectomy, right salpingo-oophorectomy, partial omentectomy, and pelvic and paraaortic lymphadenectomy were performed. Metastases of squamous cell carcinoma were confirmed in the pelvic and para-aortic lymph nodes. Six courses of adjuvant chemotherapy with paclitaxel and carboplatin were given following radical surgery to prevent the recurrence of malignant transformation of MCTO. No recurrence of the disease has been observed during 2 years of follow-up. CONCLUSION: When physicians diagnose large ovarian tumor torsion cases, preoperative examinations should be performed, with the possibility of malignancy in mind.

Ulipristal acetate for Japanese women with symptomatic uterine fibroids: A double-blind, randomized, phase II dose-finding study.

PURPOSE: A multicenter, randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy, safety, and appropriate dose of ulipristal acetate (UPA) in Japanese women with symptomatic uterine fibroids (UFs). METHODS: A total of 121 premenopausal women with UFs were enrolled to receive either placebo, UPA-2.5 mg, UPA-5 mg, UPA-10 mg, or leuprorelin acetate (LEU), a reference drug, for 12 weeks. The primary end point was the rate of patients having achieved amenorrhea for 35 days at Week 12. RESULTS: The rates for amenorrhea were 4.5%, 60.0%, 72.7%, 88.0%, and 76.2% in the placebo, UPA-2.5 mg, UPA-5 mg, UPA-10 mg, and LEU groups, respectively. The median times to amenorrhea were 20.0, 5.0, 5.0, and 23.0 days for treatment with UPA-2.5 mg, UPA-5 mg, UPA-10 mg, and LEU, respectively. A significant dose-response of UPA for the rate of amenorrhea was observed. The overall incidence rates of adverse events were 45.8% in the placebo group, 56.5%-80.0% in the UPA groups, and 100.0% in the LEU group. There were no notable safety issues with UPA. CONCLUSIONS: Ulipristal acetate was effective and well tolerated in Japanese women with UFs. The recommended dose of UPA is considered to be 10 mg.

Successful monozygotic triplet pregnancy after a single blastocyst transfer following in vitro maturation of oocytes from a woman with polycystic ovary syndrome: a case report.

BACKGROUND: Although women with polycystic ovarian syndrome (PCOS)-related sub-fertility are high responders to controlled ovarian stimulation, it is difficult to obtain mature oocytes in these women. Therefore, in vitro maturation (IVM), which is the technique of letting the contents of the ovarian follicles and the oocytes inside mature in vitro, has often been proposed in such women. We describe the first successful delivery of monozygotic triplets resulting from transfer of a single blastocyst following IVM of oocytes. CASE PRESENTATION: A 32-year-old nulligravida female with PCOS underwent IVM. She underwent vitrified-warmed single blastocyst transfer following IVM, and a dichorionic triamniotic triplet pregnancy was confirmed at 8 weeks. Healthy triplets were delivered by cesarean section at 33 weeks' gestation. This is the first case of monozygotic triplets derived from IVM oocytes that were successfully delivered. The determination of chorionicity and amnionicity is generally supposed until 3 days after fertilization, and no division or splitting of her embryo was observed on transfer. Interestingly, her embryo might have split after the transfer, resulting in a dichorionic triamniotic triplet pregnancy. CONCLUSIONS: Patients should be informed of a possible increased risk of monozygotic multiple pregnancies after single embryo transfer following IVM.

Successful Planned Pregnancy through Vitrified-Warmed Embryo Transfer in a Woman with Chronic Myeloid Leukemia: Case Report and Literature Review.

A 35-year-old female patient with chronic myeloid leukemia (CML) wanted to have a child. She had been treated with imatinib and had achieved major molecular remission, after which imatinib was intentionally discontinued, and interferon-α treatment was initiated. After three failed cycles of artificial insemination with her husband's semen, the patient underwent treatment with assisted reproductive technology. After two cycles of in vitro fertilization, two embryos (8-cell stage and blastocyst) were cryopreserved. The patient again had elevated major BCR-ABL mRNA levels; thus, infertility treatment was discontinued. After 18 months of dasatinib treatment, major molecular remission was again observed, and the patient underwent vitrified-warmed embryo transfer with a single blastocyst. After that, she became pregnant. Discontinuation of tyrosine kinase inhibitors combined with the timely initiation of infertility treatments, including assisted reproductive technology, might thus be useful for treating women with CML who wish to become pregnant.

Successful laparoscopic resection of virilizing ovarian steroid cell tumor, not otherwise specified, in a 22-year-old woman: a case report and evaluation of the steroidogenic pathway.

OBJECTIVE: Ovarian steroid cell tumor (SCT) is a rare tumor with steroid-producing ability. We report a 22-year-old woman with secondary amenorrhea and hirsutism caused by an ovarian SCT-not otherwise specified (NOS), who underwent successfully laparoscopic resection of the tumor. CASE REPORT: A 22-year-old null gravida woman presented to a hospital, having amenorrhea for 18 months and increasing facial hair. Physical examination revealed obesity (body mass index, 37.3 kg/m2) with evident facial and trunk hair. Total and free serum testosterone, and dehydroepiandrosterone sulfate levels were found to be elevated. Levels of serum adrenocorticotropic hormone, gonadotropins, cortisol, aldosterone, and ovarian steroids were observed to be within reference intervals. Although polycystic ovaries were not found, a hyperechogenic solid tumor (3 cm) was detected on transvaginal ultrasonography. Laparoscopic resection of the tumor was performed. One month post-surgery, total and free testosterone levels were observed to have decreased, and menstruation resumed two months thereafter. The patient was histologically diagnosed with ovarian SCT-NOS. Expression of ovarian steroidogenic enzymes, which are related to hyperandrogenism, was observed. No disease recurrence has been reported for more than 5 years post-surgery.

Establishing a Treatment Algorithm for Puerperal Genital Hematoma Based on the Clinical Findings.

Postpartum hemorrhage within 24 hours after delivery remains the leading cause of maternal mortality worldwide. Puerperal genital hematoma (PGHA) is a rare complication of postpartum hemorrhage, and PGHA can be life-threatening if hemostasis is not properly achieved. However, a reliable management algorithm for PGHA based on the clinical findings has not been developed. The objectives were to evaluate the management strategies for PGHA and identify the clinical findings that help select the treatment for PGHA. The medical records of women who were treated for PGHA in our department were reviewed, and data regarding the clinical findings and the treatment strategy for PGHA were analyzed. Thirty-four women who underwent treatment for PGHA were identified and divided into three groups according to the final procedure that achieved hemostasis: conservative management (CM) (n = 9), surgical management (SURG) (n = 15), and arterial embolization management (AEM) (n = 10). Regarding the clinical findings on initial evaluation, the shock index was significantly higher in the AEM group than in the CM or SURG group; and initial platelet count and fibrinogen level were significantly lower in the AEM group than in the CM group. There was no significant difference in any computed tomography (CT) finding among the three groups. In conclusion, this study clearly shows the difference in clinical findings among treatment strategies for PGHA. We suggest that the clinical findings of shock index, platelet count, and fibrinogen level together with CT findings are helpful and valuable for selecting the treatment strategy for PGHA.

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data.

BACKGROUND: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. METHODS: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause). FINDINGS: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1·55, 95% CI 1·38-1·73; p<0·0001), early menopause (age 40-44 years; 1·30, 1·22-1·39; p<0·0001), and relatively early menopause (age 45-49 years; 1·12, 1·07-1·18; p<0·0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0·0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1·88, 1·62-2·20; p<0·0001) and early menopause (1·40, 1·27-1·54; p<0·0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older. INTERPRETATION: Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as an important factor in risk stratification of cardiovascular disease for women. FUNDING: Australian National Health and Medical Research Council.

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.

Being underweight in adolescence is independently associated with adult-onset diabetes among women: The Japan Nurses' Health Study.

AIMS/INTRODUCTION: To examine the association between adult-onset diabetes and life-course bodyweight changes. MATERIALS AND METHODS: In a cross-sectional study, 17,398 Japanese female nurses aged ≥30 years completed a self-administered questionnaire in 2001-2007. Bodyweight indices were calculated for three life stages: birthweight (adjusted for gestational age), body mass index (BMI) at age 18 years and current BMI. Odds ratios for being diagnosed with adult-onset diabetes were calculated according to the combined bodyweight categories of two life stages: at birth and age 18 years; and at age 18 years and the survey (current). Path analysis was carried out to decompose the effect of each bodyweight index into direct and mediating effects. RESULTS: After adjustment for age at survey and parental diabetes history, "low" birthweight (<25th percentile), when combined with either "low" or "high" BMI (≥75th percentile) at age 18 years, had significant odds ratios (2.32, 95% confidence interval [CI] 1.22-4.44; 3.69, 95% CI 2.12-6.42, respectively) compared with the group of "middle" category (25th-74th percentile) at both life stages. The combination of "low" BMI at age 18 years and "high" current BMIs showed the highest odds ratio (7.97, 95% CI 3.97-16.00). Among women without parental diabetes history, "low" BMI at age 18 years showed a significantly high odds ratio (2.25, 95% CI 1.01-4.99), even when combined with the "middle" category of current BMI. Path analysis showed that both birthweight and BMI at age 18 years had a negative direct effect on adult-onset diabetes. CONCLUSIONS: Underweight at adolescence, as well as overweight, is a potential risk factor for adult-onset diabetes among Japanese women.

[Calcium Metabolism and Skeletal Changes during Pregnancy and Lactation.]

Calcium metabolism changes dramatically during pregnancy and lactation because offspring needs a supply of calcium. Approximately 30g of calcium, which passes through the placenta, is accumulated in a fetus during pregnancy mostly in the third trimester, and 220-340mg/day of calcium is supplied via breast milk during lactation. However, there are elaborate mechanisms to maintain maternal calcium homeostasis, which differs during pregnancy and lactation. Extra required calcium supply to the offspring in neither pregnancy nor breastfeeding normally do not cause any adverse consequences to the maternal skeleton even if any oral intake of calcium or vitamin D are increased. This article reviews the adaptation in calcium kinetics during pregnancy and lactation. Vitamin D, calciotropic hormones, and bone metabolism are also reviewed.

Safe and easy technique for the laparoscopic application of Seprafilm® in gynecologic surgery.

INTRODUCTION: Laparoscopic surgery is a minimally invasive surgery, and the rate of postoperative adhesions is low. Although Seprafilm® helps to reduce adhesions, its application in the abdominal cavity during laparoscopic surgery is difficult because of its material. Therefore, we propose an easy method for applying this adhesion barrier. MATERIALS AND SURGICAL TECHNIQUE: The Seprafilm is cut into four equal pieces. The four pieces are stacked, firmly folded twice, and grasped with the forceps. The reducer sleeve is slid over the bundle of Seprafilm. The forceps with the reducer sleeve is inserted through a 12-mm trocar near the target area. The reducer sleeve is then slid down the forceps to uncover the Seprafilm. Finally, each piece of Seprafilm is applied over the suture area. In all cases, the Seprafilm was successfully applied to the intended target. There were no cases in which Seprafilm was incompletely applied or in which it could not be used because of moistening. The average application times of surgeon 1 and surgeon 2 were 4.8 min and 5.0 min, respectively; this difference was not significant. There were no postoperative complications in any case. DISCUSSION: It is safe and easy to use our simple technique to apply Seprafilm adhesion barrier laparoscopically. Further studies are warranted to prove Seprafilm's efficacy after such application.

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BACKGROUND: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. METHODS AND FINDINGS: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. CONCLUSIONS: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Combination of microwave endometrial ablation and postoperative dienogest administration is effective for treating symptomatic adenomyosis.

AIM: Menorrhagia and dysmenorrhea are common symptoms. Uterine adenomyosis is one of the causes of menorrhagia and dysmenorrhea. These symptoms often decrease the quality of life in women. Microwave endometrial ablation (MEA) is a recently developed procedure that enables endometrial ablation. Dienogest has long been used to suppress endometrium development and reduce adenomyosis-related dysmenorrhea. However, some cases could be resistant to dienogest. In this study, we evaluated the efficacy of a combination of MEA and postoperative dienogest in reducing adenomyosis-related dysmenorrhea and menorrhagia. METHODS: Ten patients with hormone treatment-resistant symptomatic adenomyosis underwent MEA and were administered oral dienogest after the procedure. The primary endpoints were reduction in pain recurrence and anemia. The secondary endpoint was a change in the adenomyosis lesion and its symptomatic recurrence. RESULTS: Statistically significant improvements were seen in the visual analog scale score and hemoglobin levels in women post-treatment. The difference in myometrial thickness pre- and post-MEA was statistically significant. There were no cases of symptomatic recurrence. CONCLUSION: The combination of MEA and postoperative dienogest is useful for treating uterine adenomyosis with menorrhagia and dysmenorrhea.