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O Ylikorkala

Publications and source records attributed to O Ylikorkala.

At least 19 recordsLinked to original sources
PubMed2006

Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers.

BACKGROUND: Acetaminophen (paracetamol) alone or in combination with other analgesics is widely used for postoperative analgesia. While acetaminophen and non-steroidal anti-inflammatory drugs inhibit platelet function, the cyclooxygenase-2 (COX-2) selectively inhibiting coxibs show no interference with platelet function. The authors studied the effect of a combination of i.v. parecoxib and acetaminophen on platelet function in healthy volunteers. METHODS: Eighteen healthy, male volunteers (22-33 yr) received i.v. acetaminophen 1 g, parecoxib 40 mg+acetaminophen 1 g or placebo in a double-blind, crossover study. Platelet function was assessed by photometric aggregometry and by measuring the release of thromboxane B(2). Plasma acetaminophen concentrations were measured by high-performance liquid chromatography. RESULTS: Platelet aggregation (median area under the curve) triggered with arachidonic acid 500 microM was 24.6, 3.9 and 4.2x10(3) area units (P=0.02, all groups) after placebo, acetaminophen and parecoxib+acetaminophen, respectively. Inhibition of platelet aggregation showed no difference between acetaminophen alone and the combination (P=0.82). Aggregation triggered with arachidonic acid 750 or 1000 microM, adenosine diphosphate (ADP) 1.5 or 3 microM, or epinephrine 5 microM showed no differences between the groups. Release of thromboxane B(2) in response to ADP was inhibited similarly by both acetaminophen and the combination. Plasma acetaminophen concentrations were similar after acetaminophen and the combination. CONCLUSIONS: Acetaminophen and parecoxib showed no interaction in inhibiting platelet function. In combination they cause a mild degree of COX-1 inhibition corresponding to that of acetaminophen alone.

Acetaminophen↗
PubMed2006

Effects of alendronate and hormone replacement therapy, alone and in combination, on saliva, periodontal conditions and gingival crevicular fluid matrix metalloproteinase-8 levels in women with osteoporosis.

OBJECTIVE: To compare the effects of hormone replacement therapy (HRT), alendronate and their combination on oral health of elderly postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty patients, aged 65-80 years (mean 71 years), with a T-score of bone mineral density of -2.5 s.d. or less at either the lumbar spine or the femoral neck, were randomized to receive 2 mg of estradiol plus 1 mg norethisterone acetate (HRT) (n = 20), 10 mg of alendronate (n = 18), or their combination (n = 22) for 2 years. Periodontal and oral status and mouth symptoms were recorded, and salivary analyses made at the beginning and at the end of the study. Gingival crevicular fluid (GCF) matrix metalloproteinase (MMP-8) levels were determined to address destructive events in periodontal tissue. RESULTS: Resting salivary flow rate decreased by 19% (P < 0.05), and GCF MMP-8 tended to increase in the alendronate group. None of the regimens affected subjective feelings of dry or burning mouth. There were no significant changes in dental or periodontal status, stimulated flow rate or composition of saliva during the study. CONCLUSIONS: Alendronate decreased resting salivary flow rate but otherwise HRT or alendronate separately or in combination had no effect on oral health in elderly women with osteoporosis.

Aged↗
PubMed2005

Effects of oral and transdermal estradiol administration on levels of sex hormone-binding globulin in postmenopausal women with and without a history of intrahepatic cholestasis of pregnancy.

SHBG, the most important transport protein for sex steroids, is produced in the liver under the control of estrogen action. In a randomized, double-blind, prospective crossover study we compared basal levels of serum SHBG and their responses to increasing doses of oral and transdermal estradiol (E2), followed by E2 plus oral progestin (medroxyprogesterone acetate [MPA]), in 40 postmenopausal women with or without a history of intrahepatic cholestasis of pregnancy (ICP), which could affect the synthesis of SHBG. Serum samples collected at baseline, on the last day of each E2 period, and on the last day of the E2 plus MPA combination were assayed for SHBG and E2. Basal levels of SHBG showed no difference between the study groups. Oral but not transdermal E2 increased SHBG concentrations by 67-171% in the control group, but the response was smaller (42-121%) in the ICP group. Addition of MPA decreased SHBG levels by 14-18% in both groups during both treatments. In conclusion, a history of ICP is associated with blunted responses of SHBG to oral estrogen.

Administration, Cutaneous↗
PubMed2005

Hormone therapy and cardiovascular disease--still much to be learnt.

Results from the recent randomized clinical trials indicating that hormone therapy (HT) does not provide cardiovascular protection, but potential harm, are in profound disagreement with the sound evidence from numerous observational and experimental studies. While the observational studies have mainly assessed symptomatic recently menopausal women, the randomized trials have studied symptomless elderly postmenopausal women with established coronary heart disease or various risk factors for cardiovascular disease. Thus, the recent trials have revealed only that HT does not provide secondary cardiovascular benefits. Since primary cardiovascular benefits of HT are rational but not yet proven in clinical trials, new studies are in demand. Until more data from recently menopausal symptomatic women are available, we need to base our decisions on existing evidence and good clinical practice. Although the potential of HT to provide cardiovascular benefits is decreased by advancing age and time since menopause, this should not preclude the use of individualized HT in younger postmenopausal women.

Cardiovascular Diseases↗
PubMed2005

Characterization of inhibition of platelet function by paracetamol and its interaction with diclofenac in vitro.

BACKGROUND: Paracetamol (acetaminophen) is an effective analgesic and a weak inhibitor of cyclo-oxygenase (COX). Clinically paracetamol is often used together with traditional NSAIDs, which are strong inhibitors of COX. We studied binding of paracetamol to COX and its action on platelet function together with diclofenac. METHODS: Blood was collected from healthy donors and platelet function was assessed by photometric aggregometry, a platelet function analyser (PFA-100, Dade Behring, Deerfield, IL) and by measuring the release of thromboxane B(2) (TxB(2)), the stable metabolite of thromboxane A(2), after addition of paracetamol (10-80 microg ml(-1)). A concentration-inhibition relationship was established and the inhibition coefficient (K(i)) demonstrating 50% binding to COX was determined using a Schild-plot. Interaction of paracetamol (5-20 microg ml(-1)) and diclofenac (0.1-0.8 microg ml(-1)) was determined and an isobolographic analysis was performed. RESULTS: Paracetamol added to platelet-rich plasma (PRP) caused a concentration-dependent inhibition of platelet function. Photometric aggregometry and TxB(2) release was significantly inhibited by paracetamol from 10 microg ml(-1) onwards. The PFA-100 closure time was significantly prolonged by paracetamol at a high concentration only. K(i) was 15.2 microg ml(-1) with a 95% confidence interval of 11.8-18.6 microg ml(-1). Inhibition of aggregation by diclofenac was augmented by paracetamol. Isobolographic analysis showed synergism. CONCLUSIONS: The 95% confidence interval of K(i) equals the antipyretic plasma concentration of paracetamol, i.e. 10-20 microg ml(-1). High doses of paracetamol and a combination of diclofenac and paracetamol cause platelet inhibition and thus may increase risk of surgical bleeding.

Acetaminophen↗
PubMed2004

Levels of serum C-reactive protein during oral and transdermal estradiol in postmenopausal women with and without a history of intrahepatic cholestasis of pregnancy.

Liver dysfunction may affect the production and release of C-reactive protein (CRP). We designed a double-blind prospective crossover study involving 40 postmenopausal women with or without a history of intrahepatic cholestasis of pregnancy (ICP), where we compared the basal levels of CRP and their responses to increasing doses of oral and transdermal estradiol (E2), followed by addition of oral medroxyprogesterone acetate (MPA). Serum samples collected at baseline, on the last day of each E2 period, and on the last day of the E2 + MPA combination were assayed for CRP, estrogens, and liver enzymes. There was no difference in basal CRP between the study groups. Both regimens (oral and transdermal E2) were accompanied by significant rises in estrone and E2 concentrations; the former were 16 times higher during the oral than during the transdermal regimen. Oral E2 elevated CRP dose dependently, and this response was unaffected by a history of ICP or the use of MPA. The activities of liver transaminases varied but were in normal ranges during E2 use, in women with and without a history of ICP. In conclusion, the synthesis of CRP is not affected by a history of ICP. It is readily and dose dependently stimulated by oral but not by transdermal E2 in as soon as 2 wk.

Administration, Cutaneous↗
PubMed2004

Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.

Alkaline Phosphatase↗
PubMed2003

Propacetamol augments inhibition of platelet function by diclofenac in volunteers.

BACKGROUND: Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. METHODS: Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test. RESULTS: Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. CONCLUSIONS: The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.

Acetaminophen↗
PubMed2003

Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy.

BACKGROUND AND AIMS: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease. PATIENTS AND METHODS: Sixty nine Finnish ICP patients were prospectively interviewed for a family history of ICP, and clinical features were compared in patients with familial ICP (patients with a positive family history, n=11) and sporadic patients (patients with no known family history of ICP, n=58). For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP, FIC1, and MDR3. RESULTS: The pedigree structures in 16% (11/69) of patients suggested dominant inheritance. Patients with familial ICP had higher serum aminotransferase levels and a higher recurrence risk (92% v 40%). Both segregation of haplotypes and multipoint linkage analysis excluded BSEP, FIC1, and MDR3 genes in the studied pedigrees. Additionally, the MDR3 gene, previously shown to harbour mutations in ICP patients, was negative for mutations when sequenced in four affected individuals from the two families. CONCLUSIONS: These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2003

Evidence of a lack of effect of a phytoestrogen regimen on the levels of C-reactive protein, E-selectin, and nitrate in postmenopausal women.

Phytoestrogens are thought to be beneficial to vascular health. Possible mechanisms of action could involve C-reactive protein (CRP), endothelial E-selectin, and nitric oxide. We therefore designed a randomized, placebo-controlled, double-blind trial in which we studied the effects of isoflavonoids on CRP, E-selectin, and nitrate-nitrite (NO(x); reflecting the release of nitric oxide) in postmenopausal women. Fifty-six postmenopausal women (FSH > 30 U/liter) with a history of breast cancer used (in a randomized order) phytoestrogen (114 mg isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were crossed over after a 2-month washout period. The serum levels of CRP and E-selectin, and plasma levels of NO(x) were measured before and on the last day of each treatment. The phytoestrogen regimen did not affect the levels of either CRP (P = 0.584) or NO(x) (P = 0.270), but the levels of E-selectin were reduced by 4.0% (2.9 ng/ml; P = 0.031) during phytoestrogen use and by 2.2% (1.3 ng/ml; P = 0.023) during placebo use. No difference was found at any marker at 3 months between the groups. In conclusion, our data, suggesting neutral effects of phytoestrogens on CRP, E-selectin, and nitric oxide, fail to support a vasoprotective role of phytoestrogens.

Adult↗
PubMed2002

Hormone replacement therapy in women with a history of breast cancer.

Health care professionals in modern Western societies will meet an increasing number of women surviving breast cancer. How the menopause of these women should be treated is still an open question. Use of hormone replacement therapy (HRT) may, at least in theory, increase the risk for recurrence of cancer, but its categoric refusal is a double-edged sword because it also denies these women all the undisputable health benefits HRT provides. This refusal is not, however, supported by the observational data available so far on this question, because HRT has not increased the risk for breast cancer recurrence. In fact, it is well established that HRT abolishes hot flushes and improves significantly these patients' quality of life. At present, we have no effective nonhormonal alternatives for the control of vasomotor symptoms, and the efficacy of phytoestrogens in the treatment of menopausal symptoms is unproven. Selective estrogen receptor modulators (SERMs) which protect against osteoporosis and perhaps also against breast cancer, and which may have beneficial effects on the cardiovascular system, aggravate hot flushes and are therefore not useful, at least in the first postmenopausal years. In some countries, progestins are often prescribed for the control of such patients' vasomotor symptoms, but their safety has never been assessed in clinical trials, and in theory they can be harmful. Randomized clinical trials (RCT) on the use of HRT in breast cancer survivors are underway, but their completion will take years, and even these may be open to criticism. Tibolone may appear to be an appealing alternative for HRT, but it should also be studied with RCTs in this indication. At present, a patient with a history of breast cancer must be given balanced information as to the possible benefits and risks of HRT, and she herself must make the decision whether or not to start HRT.

Breast Neoplasms↗
PubMed2001

A prospective study on women with a history of breast cancer and with or without estrogen replacement therapy.

OBJECTIVE: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. METHODS: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n=54) then started using estradiol as oral tablets (2 mg/day) (n=44) or as transdermal gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients (n=34) used only estradiol, orally (2 mg/day) (n=31) or transdermally (1.5 mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. RESULTS: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9+/-8.6 to 9.9+/-6.7 (mean+/-SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14-24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%) showed no evidence of recurrence or contralateral cancer, whereas four patients had recurrence and one developed a contralateral breast cancer (5/112 woman-years, 4% per year). CONCLUSIONS: Symptomatic climacteric patients with a history of breast cancer benefited from ERT without increasing their risk of recurrence, but the short follow-up and the small number of patients limit any definitive recommendations.

Administration, Cutaneous↗
PubMed2001

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women.

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II-III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (+/-SD) follow-up time was 2.3 +/- 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 +/- 2.7 mm) to 6.8 +/- 4.2 mm at 6 months (P< 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment.

Aged↗
PubMed2001

Increased thromboxane production in women with a history of venous thromboembolic event: effect of heparins.

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia.

OBJECTIVE: Elevated amounts of circulating fetal deoxyribonucleic acid in maternal plasma have recently been detected in pregnancies complicated by preeclampsia. We attempted to confirm this finding and simultaneously examined the quantity of maternal circulating deoxyribonucleic acid. STUDY DESIGN: Circulating deoxyribonucleic acid was measured by realtime quantitative polymerase chain reaction in plasma samples obtained from 44 women with preeclampsia and a matched cohort of 53 normotensive pregnant women. RESULTS: We confirmed that circulating fetal deoxyribonucleic acid levels were significantly elevated in pregnancies complicated by preeclampsia (3194.6 vs 332.8 copies/mL; P < .001). We also showed for the first time that circulating maternal deoxyribonucleic acid levels are also elevated (219,023.9 vs 20,235.8 copies/mL; P < .001). The increases in these deoxyribonucleic acid levels corresponded to the severity of the disorder, and values were correlated with each other in pregnancies complicated by preeclampsia (r = 0.556; P < .001) but not normotensive pregnancies (r = 0.046; P = .747). CONCLUSION: The releases of both free fetal and maternal deoxyribonucleic acid were found to be affected in preeclampsia.

Birth Weight↗
PubMed2001

Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women.

OBJECTIVE: The aim of this study was to assess whether oral delivery and transdermal delivery of sequential combined hormone replacement therapy have similar effects on systemic blood pressure, as measured by 24-hour automated ambulatory recordings. STUDY DESIGN: Eighty-two healthy postmenopausal women, of whom 73 completed the study, were randomly assigned to start hormone replacement therapy with either orally (n = 38) or transdermally (n = 35) administered medication. Ambulatory blood pressure was recorded for a 24-hour period before the start of hormone replacement therapy and again 2 and 6 months later. Analysis of variance was used for data analysis. RESULTS: Hormone replacement therapy by both oral and transdermal routes was associated with slight but nonsignificant drops in mean 24-hour systolic and diastolic ambulatory blood pressure. Daytime systolic ambulatory blood pressure (mean +/- SE) fell significantly (P <.05) and similarly at 2 months in the oral (3.8 +/- 0.2 mm Hg) and transdermal (4.0 +/- 0.3 mm Hg) treatment groups. The daytime ambulatory blood pressure remained significantly lower than baseline at 6 months in the oral treatment group (-3.6 +/- 0.3 mm Hg), whereas the fall at 6 months in the transdermal group (-3.1 +/- 0.3 mm Hg) was not significant. Mean daytime diastolic ambulatory blood pressure was reduced in both the oral (-1.8 +/- 0.8 mm Hg) and transdermal (-3.5 +/- 0.7 mm Hg; P <.05) treatment groups at 2 months but not at 6 months. Nighttime ambulatory blood pressures in both groups remained unaffected by hormone replacement therapy. CONCLUSION: Sequential combined hormone replacement therapy delivered by both oral and transdermal routes caused significant falls in the daytime ambulatory blood pressure of normotensive postmenopausal women at 2 months of treatment. This fall persisted as long as 6 months of treatment in the oral treatment group but not in the transdermal treatment group.

Administration, Cutaneous↗