-
1.
Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.
Asi, N, Mohammed, K, Haydour, Q, Gionfriddo, MR, Vargas, OL, Prokop, LJ, Faubion, SS, Murad, MH
Systematic reviews. 2016;(1):121
Abstract
BACKGROUND Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model. RESULTS We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81. CONCLUSIONS Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
-
2.
Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: a double-blind, randomised study.
Polisseni, AF, Andrade, AT, Ribeiro, LC, Castro, IQ, Brandão, M, Polisseni, F, Guerra, Mde O
Maturitas. 2013;(2):172-8
Abstract
OBJECTIVE This study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women. DESIGN This study was a prospective, randomised, double-blind, comparative trial with a control group. SETTING The study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil. POPULATION A total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy. INTERVENTIONS The patients were randomised into three groups: (1) daily treatment with 2.5mg tibolone (n=64), (2) 50mg calcium carbonate+200 IU vitamin D3 (Ca/Vit D3, n=54) or (3) 1mg oestradiol+0.5mg norethindrone acetate (E2/NETA, n=56) for 12 weeks. PRIMARY OUTCOME MEASURES The primary outcome was the evaluation of QoL using the Women's Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment. RESULTS A total of 130 women in the following groups completed the study: tibolone (n=42), Ca/Vit D3 (n=44) and E2/NETA (n=44). An improved QoL based on the WHQ was observed at T0 (80.12±14.04, 77.73±15.3, 77.45±15.4) and T12 (57.0±15.5, 55.7±16.7, 58.4±12.6) for the tibolone, E2+NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2±26, 5.6±2.8, 5.4±2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2±1.5, 4.0±1.8, 4.3±2.0, respectively, p values <0.05). Adverse effects were few and mild. CONCLUSIONS An improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.
-
3.
Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.
Kurdoglu, M, Yildirim, M, Kurdoglu, Z, Erdem, A, Erdem, M, Bilgihan, A, Goktas, B
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2011;(8):551-7
Abstract
OBJECTIVE To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. METHODS The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. RESULTS Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). CONCLUSIONS Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.
-
4.
Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women.
Ziaei, S, Moghasemi, M, Faghihzadeh, S
Climacteric : the journal of the International Menopause Society. 2010;(2):147-56
Abstract
OBJECTIVE To compare the effects of tibolone with those of conventional hormone replacement therapy on climacteric symptoms and sexual function in postmenopausal women. MATERIALS AND METHODS In a randomized, controlled trial, 140 postmenopausal women were allocated into three groups. Of the subjects included, 47 women received 2.5 mg tibolone + one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily; 46 women received 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone (CEE/MPA) + one Cal+D tablet daily; and 47 women received only one Cal+D tablet as the control group. The Greene Climacteric Scale (GCS) questionnaire was used to detect the efficacy of treatment on climacteric symptoms. Rosen's Female Sexual Function Index (FSFI) was used for sexual function evaluation. Sex hormone binding globulin (SHBG), free estradiol index (FEI) and free testosterone index (FTI) were measured before and after treatment. The women were followed up for 6 months RESULTS After treatment, all subscores in the GCS improved in the tibolone and CEE/MPA groups (p < 0.01), except the sexual subscore in the CEE/MPA group, compared with baseline. There were significant differences in the FSFI in the tibolone and CEE/MPA groups in comparison to the control group after treatment. Tibolone, in comparison to CEE/MPA, significantly lowered SHBG levels and increased the FTI and FEI and improved the desire, arousal and orgasm sexual domains of the FSFI (p < 0.001). CONCLUSION Tibolone may be an alternative to conventional hormone replacement therapy in the treatment of climacteric symptoms and sexual dysfunction in postmenopausal women.
-
5.
An open-label study of subdermal implants of estradiol-only versus subdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability.
Barbosa, IC, Coutinho, EM, Oladapo, L, Noronha, CF, Mota, RL, Lopes, AC, Lopes, RC
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2009;(4):269-75
Abstract
OBJECTIVE To compare the effects of continuous 17-beta estradiol-only silastic implants with those of continuous 17-beta estradiol plus continuous nomegestrol acetate silastic implants on symptom control, lipid profile and tolerability in postmenopausal women. METHODS This was an open-label, parallel-group study. Women with and without uterus and no contraindications to hormone therapy (HT) in this study, we consider as HT the replacement of Estrogens-only and Estrogens + Progestogens Therapy, were enrolled. Each subject was assigned to receive four 17-beta estradiol-only silastic implants (women without uterus), or four 17-beta estradiol plus one nomegestrol acetate silastic implant (women with intact uterus), for 1 year. RESULTS A total of 40 subjects were enrolled and received, the silastic implants of which 40 (100.0%) subjects completed the study (n = 20, estradiol only; n = 20, estradiol plus nomegestrol acetate). The incidence of postmenopausal symptoms decreased significantly. No significant decreases in total cholesterol (1.3%), low-density lipoprotein cholesterol (1.1%), triglycerides (1.2%) and fasting glucose ((1.3%) serum levels were observed in both groups, whereas high-density lipoprotein (HDL) cholesterol increased significantly (2.8%), during the study in both groups. The incidences of adverse events were similar in both treatment groups. CONCLUSIONS Women treated with 17-beta estradiol-only silastic implants or 17-beta estradiol plus nomegestrol acetate silastic implants showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms and a significant increase in HDL cholesterol and no significant differences in other lipid profiles and tolerability.
-
6.
Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins.
Vrablik, M, Fait, T, Kovar, J, Poledne, R, Ceska, R
Metabolism: clinical and experimental. 2008;(8):1088-92
Abstract
The role of hormone replacement therapy and estrogen replacement therapy (ERT) in cardiovascular disease prevention has not been unambiguously defined yet. The metabolic effects of estrogens may vary depending upon the route of administration. Therefore, we compared the impact of unopposed oral or transdermal ERT on plasma lipids and lipoproteins in 41 hysterectomized women. This was an open-label, randomized, crossover study (with 2 treatments and 2 periods). The 41 hysterectomized women were randomized to receive oral or transdermal 17beta-estradiol in the first or second of two 12-week study periods. Plasma lipid and lipoprotein levels were assayed before and after each treatment using standard automated methods. Lipid content of lipoprotein subclasses was assessed by sequential ultracentrifugation. The atherogenic index of plasma (AIP) was calculated as log(triglyceride [TG]/high-density lipoprotein [HDL] cholesterol). The difference between the 2 forms of administration was tested using a linear mixed model. The change from baseline for each of the forms was tested using paired t test. Oral ERT resulted in a significant increase in HDL cholesterol and apolipoprotein A-I levels, whereas it significantly decreased total and low-density lipoprotein (LDL) cholesterol and increased TG concentrations. Transdermal ERT had no such effect. Oral ERT led to a significant TG enrichment of HDL (0.19 +/- 0.06 vs 0.27 +/- 0.07 mmol/L, P < .001) and LDL particles (0.23 +/- 0.08 vs 0.26 +/- 0.10 mmol/L, P < .001) compared with baseline, whereas transdermal therapy did not have any effect on lipoprotein subclasses composition. The difference between the 2 treatments was statistically significant for HDL-TG and LDL-TG (0.27 +/- 0.07 vs 0.19 +/- 0.05 mmol/L, P < .001 and 0.26 +/- 0.10 vs 0.22 +/- 0.07 mmol/L, P< .001, respectively). The transdermal but not oral ERT significantly reduced the AIP compared with baseline (-0.17 +/- 0.26 vs -0.23 +/- 0.25, P = .023), making the difference between the therapies statistically significant (-0.23 +/- 0.25 vs -0.18 +/- 0.22, P = .017). Oral administration of ERT resulted in TG enrichment of LDL and HDL particles. Transdermal ERT did not change the composition of the lipoproteins and produced a significant improvement of AIP. Compared with transdermal ERT, orally administered ERT changes negatively the composition of plasma lipoproteins.
-
7.
Effect of early estrogen replacement therapy on microvascular reactivity in patients after bilateral ovarectomy.
Prázný, M, Fait, T, Vrablik, M
Neuro endocrinology letters. 2007;(4):496-501
Abstract
OBJECTIVES The aim of the study was to evaluate skin microvascular reactivity (MVR) measured by laser Doppler flowmetry in women early after bilateral ovarectomy treated with oral and transdermal estrogen replacement therapy (ERT). DESIGN Interventional, randomized study with a cross-over design. PATIENTS AND METHODS 41 patients (49+/-6 years, 6-12 weeks after surgical castration) were treated with 17-beta-estradiol transdermally (0.05 mg/day) or orally (2 mg/day) for three months and 20 healthy female subjects (47+/-5 years) served as controls. RESULTS Records of laser Doppler flowmetry were blinded prior to the evaluation. Maximal perfusion and velocity of perfusion increase during post-occlusive reactive hyperemia (PORH) were lower before ERT comparing to controls at baseline (36+/-16 vs. 48+/-18 PU, p<0.05, and 2.8+/-1.9 vs. 4.2+/-2.3 PU, p<0.05, respectively). Velocity of perfusion increase in PORH decreased after oral ERT compared to baseline and also to transdermal ERT (2.1+/-1.2 vs. 2.8+/-1.9 PU.s-1, p<0.05, and vs. 3.5+/-3.2 PU.s-1, p<0.01, respectively), nonsignificant increase of this parameter after transdermal ERT led to normalization when comparing to control group (3.6+/-3.2 vs. 4.2+/-2.3 PU.s-1, NS). Increase of HDL-cholesterol and decrease of LDL-cholesterol (2.1+/-0.4 vs. 1.8+/-0.4 mmol.l-1, p<0.01, and 2.5+/-0.7 vs. 3.1+/-1.0 mmol.l-1, p<0.01) was observed after oral ERT while HDL-cholesterol increase after transdermal ERT was less pronounced (1.96+/-0.42 mmol.l-1, p<0.05). LDL-cholesterol levels did not change. A correlation between HDL-cholesterol and maximal post-occlusive flow expressed in % of basal perfusion was observed in patients before treatment (r=0.47, p=0.002). CONCLUSIONS Microvascular reactivity is impaired in women early after bilateral ovarectomy. No statistically significant improvement of MVR was observed after oral estrogen replacement therapy, normalization of MVR after transdermal ERT was only partial. Changes of MVR and lipid profile differed between oral and transdermal routes of estrogen replacement therapy.
-
8.
[Profiles of irregular bleeding induced by low-dose hormone therapy and Chinese formulated herbs products].
Wang, SH, Lin, SQ, Gui, QF, Jin, MJ, Jiang, Y
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2006;(2):256-61
Abstract
OBJECTIVE To compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products. METHODS Applied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding. CONCLUSION Profiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.
-
9.
A comparison of oral and transdermal short-term estrogen therapy in postmenopausal women with metabolic syndrome.
Chu, MC, Cosper, P, Nakhuda, GS, Lobo, RA
Fertility and sterility. 2006;(6):1669-75
Abstract
OBJECTIVE To determine whether it would be preferable to prescribe oral or transdermal estrogen to symptomatic postmenopausal women with metabolic syndrome (MBS). DESIGN Prospective, randomized study. SETTING Academic medical center. PATIENT(S): Fifty obese postmenopausal women with MBS. INTERVENTION(S): Women were randomized to receive either oral E(2) (oE(2), 1 mg/d) or transdermal E(2) (tE(2), 0.05 mg/d) for 3 months. Fasting blood was obtained before and after treatment for glucose, insulin, lipid profiles, the adipocytokines (adiponectin, leptin, and resistin), and a gastric peptide (ghrelin). In addition, a 75-g 2-hour oral glucose-tolerance and intravenous insulin-tolerance tests were performed before and after E(2). MAIN OUTCOME MEASURE(S): Changes in parameters of insulin resistance (IR), lipid profiles, and adipocytokine levels. RESULT(S): Mean serum concentrations of E(2) in women using oE(2) and tE(2) were 39.1 +/- 5.6 and 49.2 +/- 28.6 pg/mL, respectively. After oE(2), there was a statistically significant worsening of IR markers, including an increase in baseline insulin (15.28 +/- 1.27 to 22.02 +/- 2.40 microU/mL), a reduction in quantitative insulin-sensitivity check index (0.3177 +/- 0.0043 to 0.2977 +/- 0.0057), and an increase in homeostasis model assessment (3.96 +/- 0.38 to 8.59 +/- 2.08). The only significant change in the lipid profile was an increase in high-density-lipoprotein cholesterol (50.46 +/- 2.34 vs. 55.08 +/- 2.51 mg/dL). Leptin levels increased (81.43 +/- 7.87 ng/mL to 94.10 +/- 6.56 ng/mL), and adiponectin decreased nonsignificantly, resulting in an increased leptin-adiponectin ratio (12.56 +/- 1.70 to 15.86 +/- 2.24); resistin levels increased (9.37 +/- 1.09 ng/mL to 11.72 +/- 1.10 ng/mL); and baseline ghrelin levels decreased (701.64 +/- 59.79 pg/mL to 581.72 +/- 36.07 pg/mL). After tE(2), no significant changes in IR parameters occurred, except for a decrease in glucose-insulin ratio. There were no changes in lipid parameters. Leptin did not change (72.7 +/- 9.3 ng/mL to 78.8 +/- 7.9 ng/mL), whereas adiponectin levels showed statistically significant increase (7.97 +/- 0.7 microg/mL vs. 9.96 +/- 1.1 microg/mL), with no change in the leptin-adiponectin ratio. Resistin levels did not change significantly, and ghrelin levels decreased (888.52 +/- 109.98 pg/mL vs. 579.04 +/- 39.30 pg/mL). CONCLUSION(S): This short-term study suggests that oral E(2) may worsen IR and adipocytokine parameters, worsening cardiovascular risk. Transdermal E(2) had minimal effects on IR and resulted in higher adiponectin. Although these data may not reflect alterations that occur with estrogen therapy in more metabolically normal postmenopausal women or with longer term therapy, the findings suggest that tE(2) may be a preferable treatment for obese women with MBS. Long-term studies are needed to make any recommendations.
-
10.
Effect of different preparations of hormone therapy on lipid and glucose metabolism, coagulation factors, and bone mineral density in overweight and obese postmenopausal women.
Osmanağaoğlu, MA, Osmanağaoğlu, S, Osmanağaoğlu, T, Okumuş, B, Bozkaya, H
Fertility and sterility. 2005;(2):384-93
Abstract
OBJECTIVE To determine the effects of different preparations of hormone therapy (HT) on lipid and glucose metabolism, coagulation factors, and bone mineral density (BMD) in overweight and obese postmenopausal women. DESIGN A randomized, nonblinded, controlled study. SETTING Karadeniz Technical University, Department of Obstetrics and Gynecology. PATIENT(S): A total of 352 overweight and obese (body mass index >25 kg/m2) postmenopausal women. INTERVENTION(S): Ninety women received 2.5 mg of tibolone; 84 received 2 mg of E2 plus 1 mg of norethisterone acetate (E2/NETA); 90 received 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (CEE/MPA); and 88 did not receive any menopausal therapy (control). MAIN OUTCOME MEASURE(S): At baseline and after 6 months of treatment, we measured total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), insulin, glucose, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein S, protein C, fibrinogen, and BMD at the lumbar spine L1-L4. RESULT(S): There were no statistically significant differences among the groups for any variables at baseline. After 6 months of treatment, the three regimens decreased total cholesterol, triglyceride, LDL, and fibrinogen; E2/NETA and CEE/MPA increased HDL, and tibolone decreased HDL; higher insulin concentrations were found in the control and tibolone groups. Body mass index, HDL, fibrinogen levels, and L1-L4 BMD were independent factors in the prediction of HT use. CONCLUSION(S): Body mass index, HDL, fibrinogen levels and L1-L4 BMD were independent factors in the prediction of HT use. Treatment with tibolone, E2/NETA, and CEE/MPA resulted in minimal improvement in lumbar spine BMD but had a beneficial effect on the procoagulation system, with minimal changes in glucose metabolism after 6 months of therapy.