In a prospective, randomized, placebo-controlled 12-wk study, we investigated the effect of oral hormone replacement therapy on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), and an independent risk factor for coronary heart disease. The effects on arginine and symmetric dimethylarginine were also investigated. Sixty healthy early postmenopausal women received daily placebo (n = 16) or oral 17beta-estradiol 2 mg, either unopposed (E(2); n = 16) or sequentially combined with dydrogesterone 10 mg (E(2)+D; n = 14) or trimegestone 0.5 mg (E(2)+T; n = 14). ADMA levels reduced in all active treatment groups. Compared with baseline and placebo, the largest reduction in ADMA levels was observed in the E(2)+T group [-18.7% (95% confidence interval [CI], -25.4 to -11.9%) and -21.1% (95% CI, -26.2 to -16.1%), at 4 and 12 wk, respectively]. At 4 and 12 wk in the E(2)+T group, arginine levels were significantly reduced as well [-30.9% (95% CI, -41.1 to -20.7%) and -36.3% (95% CI, -43.1 to -29.5%), respectively], whereas symmetric dimethylarginine levels were significantly lower in the E(2)+D group after 12 wk [-11.6% (95% CI, -19.9 to -3.3%)]. In conclusion, unopposed oral estradiol and estradiol combined with dydrogesterone or trimegestone reduced plasma levels of the NOS inhibitor ADMA. Whether the reduction of the NOS substrate arginine in the E(2)+T group counteracts the potentially beneficial effect of ADMA reduction or reflects increased NO production remains to be investigated.

Traditionally, it is understood that dizygotic (DZ) twins always have a dichorionic placenta. However, with 8% blood chimerism in DZ twins, placental sharing is probably more common than previously has been recognized. In this article, we will review all available cases of monochorionic dizygotic (MCDZ) twins. A total of 31 twins have been described in literature. A monochorionic diamniotic placenta is reported in all cases. Assisted reproductive technology is responsible for the origin of the pregnancy in 82.1% of the cases. In 15.4% of the sex-discordant twins, a genital anomaly was reported in one of the twins. Chimerism is demonstrable in 90.3% of the twins, leading to various diagnostic difficulties. As this review shows that most MCDZ twins are discovered by accident, it can be argued that it is far more common than has been assumed until now. However, the prevalence is still unclear. Awareness of MCDZ twinning is important, with subsequently correct medical strategies. Similarly, the resulting (blood) chimerism is essential to consider in diagnostic procedures, pre- and postnatally. More research on the effect of placental transfusion between sex-discordant twins is required.

The supplement containing soy isoflavones and A racemosa L. had no statistically significant effect on climacteric symptoms in perimenopausal women experiencing at least five vasomotor symptoms per day.

The ID-LC-MS/MS assay measures serum testosterone with acceptable accuracy and is useful in female samples, supporting the conclusion that the postmenopausal ovary contributes to circulating testosterone. To our knowledge, our analytical method compares favourably to similar published methods in terms of sensitivity. The sensitivity and specificity of this method comply with the reference method for measurement of testosterone in serum samples of women, children and men suffering from hypogonadism and can also be used for men with testosterone in the reference range.

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Abstract. Verhoeven MO, Hemelaar M, van der Mooren MJ, Kenemans P, Teerlink T (Project 'Ageing Women' and the Institute for Cardiovascular Research-Vrije Universiteit; and VU University Medical Center; Amsterdam, the Netherlands). Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebocontrolled study. J Intern Med 2006; 259: 199-208. Objective. To compare the effects of oral and transdermal hormone therapy (HT) on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in postmenopausal women. Design. In a multicentre, placebo-controlled, double-blind study, 152 hysterectomized healthy women were randomized to receive daily transdermal 17b-oestradiol (tE 2 , n ¼ 33), or oral micronized 17b-oestradiol either unopposed (oE 2 , n ¼ 37), or continuous combined with gestodene (oE 2 + G, n ¼ 33), or placebo (n ¼ 49) for 13, 28-day treatment cycles. Plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured at baseline and in treatment cycles 4 and 13 with a high-performance liquid chromatography method. Results. After 13 cycles all active treatment groups showed a significant reduction in ADMA compared with placebo: tE 2 , )4.0% (95% CI: )7.5 to )0.6%); oE 2 , )7.7% (95% CI: )10.9 to )4.4%) and oE 2 + G, )7.5% (95% CI: )10.8 to )4.3%). ancova showed a significantly larger reduction in the oral groups compared with the transdermal group (tE 2 vs. oE 2 and tE 2 vs. oE 2 + G, both P < 0.01). Oral, but not transdermal treatment, significantly reduced arginine compared with placebo. All active treatments reduced SDMA; however, this was only statistically significant in the oE 2 group. Conclusion. Reduction of ADMA was more pronounced after oral than after tE 2 administration. Adding gestodene to oral 17b-oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17b-oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.Keywords: arginine, asymmetric dimethylarginine, gestodene, oestradiol, postmenopausal, symmetric dimethylarginine.Abbreviations: ADMA, asymmetric dimethylarginine; an(c)ova, analysis of (co)variance; BMI, body mass index; CEE, conjugated equine oestrogens; CHD, coronary heart disease; CI, confidence interval; CRP, C-reactive protein; DDAH, dimethylarginine dimethylaminohydrolase; E 2 , oestradiol; FSH, follicle-stimulating hormone; HDL, high-density lipoprotein; HT, hormone therapy; LDL, low-density lipoprotein; NO, nitric oxide; NOS, nitric oxide synthase; oE 2 , oral micronized 17b-oestradiol 1 mg; oE 2 + G, oral micronized 17b-oestradiol 1 mg continuously combined with gestodene 25 lg; PRMTs, protein arginine methyltransferases; SDMA, symmetric dimethylarginine; sE-selectin, soluble E-selectin; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular cell adhesion molecule-1; tE 2 , transdermal 17b-oestradiol...

The CHD risk profile was affected unfavorably by both physiological and surgical menopause. Changes in most CHD risk markers were small, despite the substantial changes in hormonal parameters.

STUDY QUESTION Is there an increased prevalence of male microchimerism in women with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, as evidence of fetal exposure to blood and anti-Müllerian hormone (AMH) from a (vanished) male co-twin resulting in regression of the Müllerian duct derivatives? SUMMARY ANSWER Predominant absence of male microchimerism in adult women with MRKH syndrome does not support our hypothesis that intrauterine blood exchange with a (vanished) male co-twin is the pathophysiological mechanism. WHAT IS KNOWN ALREADY The etiology of MRKH is unclear. Research on the phenotype analogous condition in cattle (freemartinism) has yielded the hypothesis that Müllerian duct development is inhibited by exposure to AMH in utero . In cattle, the male co-twin has been identified as the source for AMH, which is transferred via placental blood exchange. In human twins, a similar exchange of cellular material has been documented by detection of chimerism, but it is unknown whether this has clinical consequences. STUDY DESIGN, SIZE, DURATION An observational case–control study was performed to compare the presence of male microchimerism in women with MRKH syndrome and control women. Through recruitment via the Dutch patients’ association of women with MRKH (comprising 300 members who were informed by email or regular mail), we enrolled 96 patients between January 2017 and July 2017. The control group consisted of 100 women who reported never having been pregnant. PARTICIPANTS/MATERIALS, SETTING, METHODS After written informed consent, peripheral blood samples were obtained by venipuncture, and genomic DNA was extracted. Male microchimerism was detected by Y-chromosome–specific real-time quantitative PCR, with use of DYS14 marker. Possible other sources for microchimerism, for example older brothers, were evaluated using questionnaire data. MAIN RESULTS AND THE ROLE OF CHANCE The final analysis included 194 women: 95 women with MRKH syndrome with a mean age of 40.9 years and 99 control women with a mean age of 30.2 years. In total, 54 women (56.8%) were identified as having typical MRKH syndrome, and 41 women (43.2%) were identified as having atypical MRKH syndrome (when extra-genital malformations were present). The prevalence of male microchimerism was significantly higher in the control group than in the MRKH group (17.2% versus 5.3%, P = 0.009). After correcting for age, women in the control group were 5.8 times more likely to have male microchimerism (odds ratio 5.84 (CI 1.59–21.47), P = 0.008). The mean concentration of male microchimerism in the positive samples was 56.0 male genome equivalent per 1 000 000 cells. The prevalence of male microchimerism was similar in women with typical MRKH syndrome and atypical MRKH syndrome (5.6% versus 4.9%, ...