W.M. van Baal

Effects of hormone replacement therapy on blood platelets.

Background Hormone replacement therapy (HRT) increases the risk of cardiovascular morbidity in postmenopausal women under certain circumstances. Part of this effect may be the result of the influence of HRT on blood platelets. We studied the effect of short‐term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women.

Effects of transdermal and oral postmenopausal hormone therapy on vascular function a randomized placebo-controlled study in healthy postmenopausal women

Objective: To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women. Design: In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 μg of transdermal 17ß-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 μg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness). Results: Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery. Conclusions: Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.

Postmenopausal oestradiol-dydrogesterone therapy favourably affects fibrinolysis and Lp(a) in healthy women

Background: Impaired fibrinolysis and increased lipoprotein (a) [Lp(a)] are major elements in the pathogenesis of atherothrombotic events. This study was undertaken to investigate the long-term effects of oestradioldydrogesterone therapy on fibrinolysis and lipoprotein (a) in healthy postmenopausal women. Methods: 27 women were randomized into a hormone-replacement therapy (HRT) group (n=14) and a control group (n=1313). During the first 12 months, the HRT group was treated with oral 17β-oestradiol (E2), 1 mg daily, sequentially combined with dydrogesterone 5 or 10 mg daily (14 days per 28-day treatment cycle). Thereafter these women received oral E2, 2 mg daily, sequentially combined with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Results: At baseline no significant differences were noted between the two groups. As compared to the control group (ANOVA for repeated measures with the baseline value as covariate), 15 months of HRT was associated with lower levels of plasma plasminogen activator inhibitor-1 (−26%; P=0.02) and serum Lp(a) (−46%; P<0.01), as well as with higher levels of plasma plasmin-antiplasmin (PAP) complexes (+8%; P=0.02). After 12 months of treatment with the 1 mg E2 regimen, similar significant results were found, except for PAP complexes. When compared to no treatment, HRT was not associated with differences in plasma levels of tissue plasminogen activator, thrombin-antithrombin complexes, prothrombin fragment 1+2, factor Vllc or factor Vlla. Conclusions: Long-term sequentially combined E2-dydrogesterone increases fibrinolytic potential and decreases serum Lp(a) levels without deterioration of the coagulation markers measured.

WS17: Newcomers WS17‐01Hormone replacement therapy reduces impedance to flow in different vascular beds

An HRT‐associated reduction of the pulsatility index (PI) has been reported in the literature, although cross‐sectional studies have shown conflicting data. In a prospective, controlled study we randomized 30 healthy postmenopausal women (mean age 52 ± 3 years) into two groups. Women in the HRT group (N = 15) received 1 mg micronized 17β‐estradiol daily (E2) sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28‐day cycle during 12 months, and, thereafter, 2 mg E2 combined with 10 mg dydrogesterone for a period of 3 months. The control group (N = 15) received no treatment. Color Doppler ultrasound was used to measure the impedance to flow (pulsatility index [PI]) within the uterine, central retinal and ophthalmic arteries in the E2‐phase at baseline and after 3, 12 and 15 months. Compared to controls, 12 months of HRT was associated with a significant decrease in the mean PI of the uterine artery of −39% (HRT −25%, controls +14%) and in that of the central retinal artery of −29% (HRT −9%, controls +20%). After 3 months this effect was already evident. During HRT, the reductions in mean PI of the uterine and central retinal arteries vs. baseline were larger (both P = 0.002) in the women with high pretreatment PI values when compared to those with low pretreatment values. The baseline PI of the uterine artery correlated positively with age and with duration of amenorrhoea (r = 0.42, P = 0.01 and r = 0.48, P = 0.008, respectively). Our 12‐month study expanded on earlier reports of a reduced PI of the uterine artery. We used a combined regimen containing a low‐dose of oestrogens. These results are important because the recent trend is to recommend combined HRT that contain lower dosages of oestrogens than before. Furthermore, a 29% reduction of the PI of the central retinal artery was observed, which suggests that HRT has a positive influence on the impedance of the cerebral circulation. From the point of view of atherothrombotic risk these observations are beneficial and possibly helpful in understanding the decreased risk of cardiovascular disease, and of the impairment of cognitive functions associated with oestrogens in epidemiological data.

III.5 Saline infusion sonohysterography is a good approach for additional assessment of the endometrium

Abstract We describe the results of endometrial assessment with transvaginal ultrasound (TVU) and saline infusion sonohysterography (SIS) in healthy, asymptomatic early postmenopausal women. We used cross-sectional data obtained from women who were screened prior to participation in a clinical trial for prevention of osteoporosis, with either hormone replacement therapy, placebo or a selective oestrogen receptor modulator.