Follow-up of women after a first episode of postmenopausal bleeding and endometrial thickness greater than 4 millimeters.

OBJECTIVE: To estimate the incidence of recurrent postmenopausal bleeding among women who were diagnosed with an endometrial thickness greater than 4 mm. METHODS: We designed a prospective cohort study and included consecutive women not using hormone replacement therapy, presenting with a first episode of postmenopausal bleeding. We evaluated patients who had an endometrial thickness greater than 4 mm at transvaginal ultrasonography and benign endometrial sampling; presence of carcinoma was ruled out by office endometrial sampling, hysteroscopy, and/or dilation and curettage. Time until recurrent bleeding was measured, and diagnosis at recurrent bleeding was recorded. RESULTS: Among 318 patients who had an endometrial thickness greater than 4 mm, 222 patients had benign histology results and were available for follow-up. During follow-up, 47 (21%, 95% confidence interval 16-27%) patients had recurrent bleeding, with a median time to recurrent bleeding of 49 weeks (interquartile range 18 to 86 weeks). There was no difference with respect to recurrence rate between patients with polyp removal, patients with a normal hysteroscopy, and patients with office endometrial sampling alone at the initial workup. Two patients were diagnosed with atypical endometrial hyperplasia upon recurrent bleeding. CONCLUSION: The recurrence rate of postmenopausal bleeding in women with endometrial thickness greater than 4 mm is 20%. This recurrence rate is not related to incorporation of hysteroscopy or polyp removal at the initial workup. LEVEL OF EVIDENCE: II.

Oral, more than transdermal, estrogen therapy improves lipids and lipoprotein(a) in postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: To assess the effects of low-dose oral and transdermal estrogen therapy on the lipid profile and lipoprotein(a) [Lp(a)] levels in healthy, postmenopausal women and to study the additional influence of gestodene administration. DESIGN: In a multicenter, randomized, double-blind, placebo-controlled study, 152 healthy, hysterectomized, postmenopausal women received daily either placebo (n = 49), 50 microg transdermal 17beta-estradiol (tE2, n = 33), 1 mg oral 17beta-estradiol (oE2, n = 37), or 1 mg oE2 combined with 25 microg gestodene (oE2 + G, n = 33) for 13 cycles of 28 days, followed by 4 cycles of placebo in each group. Fasting serum concentrations of total, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, triglycerides, and Lp(a) were measured at baseline and in cycles 4, 13, and 17. RESULTS: In cycle 13, a significant mean percentage decrease from baseline was found in all treatment groups compared with placebo in total cholesterol (tE2, -4.7%; oE2, -6.9%; oE2 + G, -10.5%) and LDL cholesterol (tE2, -5.8%; oE2, -12.6%; oE2 + G, -13.6%). For both oral groups, the reductions were already significant in cycle 4. None of the treatment groups showed a significant change in HDL cholesterol or triglycerides. In cycle 13, Lp(a) was decreased compared with placebo in the oE2 group (-6.6%) and the oE2 + G group (-8.2%). After washout, all observed changes had returned to baseline level, except for the decreases in total and LDL cholesterol in the oE2 + G group. CONCLUSIONS: Oral E2 and E2 + G, and to a lesser extent transdermal E2, decreased total and LDL cholesterol. Lp(a) was lowered only by the oral treatments.

The effects of 17 beta-oestradiol plus dydrogesterone compared with conjugated equine oestrogens plus medroxyprogesterone acetate on lipids, apolipoproteins and lipoprotein(a).

OBJECTIVE: To compare the effects of 17 beta-oestradiol plus dydrogesterone with conjugated equine oestrogens plus medroxyprogesterone acetate on serum lipids, apolipoproteins and lipoprotein(a) in postmenopausal women. METHODS: A multi-centre, prospective, randomised, double-blind, comparative one-year study in 362 healthy postmenopausal women aged 39-74 years with an intact uterus. Fasting blood samples were taken at baseline and after 28 and 52 weeks of treatment. Participants received daily oral treatment with continuous combined 1 mg micronised 17 beta-oestradiol/5 mg dydrogesterone (E/D: n=180) or 0.625 mg conjugated equine oestrogens/5 mg medroxyprogesterone acetate (CEE/MPA: n=182). RESULTS: Significant differences between the two groups after 52 weeks were observed for total cholesterol (E/D: -1.7%; CEE/MPA: -7.3%), LDL-cholesterol (E/D: -4.5%; CEE/MPA: -11.3%), HDL-cholesterol (E/D: +15.3%; CEE/MPA: +7.5%), triglycerides (E/D: +9.8%; CEE/MPA: +16.6%), VLDL-triglycerides (E/D: -3.3%; CEE/MPA: +10.0%), lipoprotein(a) (E/D: 0.0%; CEE/MPA: -25.2%) and for the ratio apolipoprotein B/LDL-cholesterol (E/D: +0.9%; CEE/MPA +5.9%). CONCLUSIONS: E/D and CEE/MPA differ in their anti-atherogenic effects on lipids and lipoproteins. This however can not easily be translated to differences in clinical cardiovascular outcomes.

Short-term effects of two continuous combined oestrogen-progestogen therapies on several cardiovascular risk markers in healthy postmenopausal women: a randomised controlled trial.

OBJECTIVE: To compare the short-term effects of two oral continuous combined oestrogen-progestogen treatment regimens on blood concentrations of several cardiovascular risk markers in healthy postmenopausal women. STUDY DESIGN: In a 12-week randomised controlled study, 48 healthy non-hysterectomised postmenopausal women, aged 41-58 years, received either no treatment (control group; n=16), or daily oral continuous combined treatment with 1 mg micronised 17beta-oestradiol plus 5 mg dydrogesterone (E/D group; n=18) or 0.625 mg conjugated equine oestrogens plus 5 mg medroxyprogesterone acetate (CEE/MPA group; n=14). Fasting blood sampling was performed at baseline and after 12 weeks of follow-up. RESULTS: Compared with the control group, 12-week treatment with E/D or CEE/MPA reduced fibrinogen (-7.7%, p=0.004 and -3.3%, p=0.083, respectively), factor VII-act (-8.7%, p=0.14 and -9.7%, p=0.06, respectively), homocysteine (-20.5%, p=0.02 and -26.7%, p=0.005, respectively), and IGF-1 (-27.9%, p<0.001 and -18.1%, p=0.002, respectively), but increased factor VII-ag (+10.1%, p=0.03 and +4.4%, p=0.46, respectively), endothelin-1 (+15.2%, p=0.12 and +20.0%, p=0.13, respectively) and C-reactive protein (+88.8%, p=0.18 and +71.0%, p=0.44, respectively). Fibrinolytic factors were not affected by either hormone therapy (HT). CONCLUSIONS: Short-term oral continuous combined therapy with oestradiol/dydrogesterone and conjugated equine oestrogens/medroxyprogesterone acetate had comparable effects on the investigated cardiovascular risk markers.

Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study.

OBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.