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P Kenemans

Publications and source records attributed to P Kenemans.

At least 55 records · Page 3Linked to original sources
PubMed2000

Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations.

OBJECTIVES: BRCA1 and BRCA2 germline mutations increase the risk of ovarian and breast cancer. Fallopian tube cancer has occasionally been observed in breast-ovarian cancer families. At our family cancer clinic we recently encountered two cases of Fallopian tube cancer within two families harboring a BRCA1 germline mutation. To study the relationship between Fallopian tube cancer and BRCA1 mutations, a histopathological reevaluation and molecular analysis were performed. METHODS: Medical and histopathological reports of the Fallopian tube cancer cases as well as archival tissue blocks were retrieved. The histopathological diagnoses were reevaluated. We investigated whether patients with Fallopian tube cancer had been carriers of a BRCA germline mutation. In addition we investigated whether loss of the wild-type allele had occurred in the tumor. RESULTS: In 2 of 23 families with a known BRCA1 mutation from our family cancer clinic, a case of Fallopian tube cancer was reported. Histological reevaluation confirmed the diagnosis of Fallopian tube cancer in both cases. In one case Fallopian tube cancer may have been part of a multifocal primary malignancy. In both patients the presence of a BRCA1 mutation was confirmed in the germline. Furthermore, we showed loss of the wild-type BRCA1 allele in both tumors. CONCLUSIONS: These findings provide the first molecular evidence that Fallopian tube cancer may be due to germline mutations in BRCA1. This may have important consequences for the preferred method of prophylactic oophorectomy in BRCA1 mutation carriers.

Adult↗
PubMed2000

Sentinel node detection in cervical cancer.

BACKGROUND: For superficial tumors such as melanoma, breast, and vulvar cancer, sentinel node detection prevents unnecessary extensive lymph node dissections. Sentinel node detection has not yet proved feasible in tumors, such as cervical cancer, that drain to deep pelvic lymph nodes. TECHNIQUE: We injected technetium-99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy and intraoperative gamma probe detection of sentinel nodes. For visual detection, blue dye was injected at the start of surgery. EXPERIENCE: In six of 10 eligible women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe detection was successful in eight of ten women, whereas visual detection found sentinel nodes in only four. They were found as far as the common iliac level. One woman had positive lymph nodes, of which one was a sentinel node. CONCLUSION: Identification of sentinel nodes using radionuclide is possible in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided.

Adult↗
PubMed2000

Cancer risk associated with subfertility and ovulation induction: a review.

OBJECTIVE: Over the past decades the use of fertility drugs (FDs) has greatly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically review the available epidemiologic studies. METHODS: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancers of the ovary, breast, endometrium and thyroid, and melanoma. RESULTS: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in epidemiologic studies. With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal. The most important sources of bias are inadequate confounder control for both parity and causes of subfertility. CONCLUSIONS: To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time. In such cohort studies the cause of subfertility should be measured adequately (based on medical records) and information about reproductive characteristics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not so treated.

Adolescent↗
PubMed2000

Ultrasound assessment of the endometrium in healthy, asymptomatic early post-menopausal women: saline infusion sonohysterography versus transvaginal ultrasound.

OBJECTIVE: To exclude pre-existing endometrial pathology in asymptomatic early post-menopausal women before starting hormone replacement therapy by transvaginal ultrasound (TVS) and saline infusion sonohysterography (SIS). METHODS: In a cross-sectional study, 148 healthy women (mean age, 51.1 years; range, 46-59 years) underwent ultrasound evaluation of the endometrium before participation in a clinical trial. TVS was used to measure double-layer endometrial thickness. SIS was performed at the same visit to measure anterior and posterior single-layer endometrial thickness, and to identify endometrial abnormalities when present. Ultrasound results were defined as informative if the endometrium could be adequately visualized. Findings on TVSs were defined as abnormal if a double-layer endometrial measurement > 5.0 mm was obtained. Findings on SIS were defined as abnormal if one or both single layers of the endometrium measured > 2.5 mm, or if focal endometrial thickening or a polyp was present. RESULTS: Of the 148 eligible women, informative TVS results were obtained from 134 women, SIS results from 133 women and both procedures combined from 119 women. TVS scans gave abnormal results in 8.2% of women (11 of 134) and SIS gave abnormal results in 36.8% of women (49 of 133). Of the 14 women with a non-informative TVS, eight had abnormal SIS results. Of the 15 women with a non-informative SIS, three had abnormal TVS results. In the 119 women with both informative TVS and SIS, abnormal TVS scans were found in 6.7% of women (eight of 119) and abnormal SIS in 34.5% of women (41 of 119). All eight women with abnormal TVS had an abnormal SIS, whereas 29.7% (33 of 111) of the women with a normal TVS had an abnormal SIS. CONCLUSIONS: Ultrasound evaluation demonstrated endometrial abnormalities in 34.5% (41 of 119) of asymptomatic post-menopausal women. SIS is more accurate than TVS in the detection of endometrial abnormalities.

Endometrium↗
PubMed2000

Clinical equivalence of intranasal and oral 17beta-estradiol for postmenopausal symptoms.

OBJECTIVE: The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug. STUDY DESIGN: In this multinational, double-blind, parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were randomly assigned to receive either 300 microg/d intranasal 17beta-estradiol (S21400) or 2 mg/d oral micronized estradiol, plus the appropriate placebo, for 24 weeks. All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle. Adjustment of intranasal dosage was permitted from week 14 on. The primary efficacy criterion was the Kupperman index at week 14, with a predefined limit of equivalence of 4. RESULTS: Kupperman index scores improved similarly in the 2 groups, from 28.4 +/- 6.2 to 10.0 +/- 8.6 (mean +/- SD) for S21400 and from 28.1 +/- 6.0 to 8.9 +/- 8.0 for oral therapy, with a difference between groups at week 14 of 1.1 +/- 0.6 (90% confidence interval, 0. 0 to 2.2). This was below the predefined equivalence limit of +4 for statistical noninferiority (P <.001). The daily number and intensity of hot flushes decreased similarly in the two treatment groups. Withdrawal bleeding was 20% less frequent with intranasal therapy (90% confidence interval, 12.5 to 27.6). Severe mastalgia was less frequent in the S21400 group (1.0%) than in the group with oral therapy (5.2%; P <.01). Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400. The same number of patients required dose adaptation in the 2 groups (approximately 20%). CONCLUSION: Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms, with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect.

Administration, Intranasal↗
PubMed2000

High risk human papillomavirus in women with normal cervical cytology prior to the development of abnormal cytology and colposcopy.

OBJECTIVE: To study the significance of the presence of high risk human papillomavirus (HPV) in women with initially normal cervical cytology for the development of abnormal cytology and an abnormal colposcopic impression. DESIGN: Prospective, observational study PARTICIPANTS AND METHODS: Sixty-eight women with cytomorphologically normal smears and at least one positive HPV test result were evaluated every six months by cytology, colposcopy and HPV testing. The endpoint of the study was abnormal cervical cytology. RESULTS: The median time of follow up from the first positive HPV test was 34 months. A total of 17 women developed abnormal cytology, of whom 16 (94%) had persistence of a high risk HPV infection. Women with persistent high risk HPV were more likely to develop abnormal cervical cytology than women without high risk HPV (hazard ratio 28.2, 95% CI 3.72-215.2); they also had an increased risk of developing an abnormal colposcopic impression (hazard ratio 4.4, 95% CI 1.69-11.7). Among the 17 women with abnormal cytology, high grade dysplasia was histopathologically demonstrated in eight women. CONCLUSION: Persistent presence of high risk HPV in normal cervical smears is associated with a significantly increased risk of developing abnormal cytology and to a lesser degree with developing an abnormal colposcopic impression.

Adolescent↗
PubMed2000

Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Adolescent↗
PubMed2000

Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study.

UNLABELLED: In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group). RESULTS: As compared to placebo, plasma levels of AT III were reduced only in the E2 group (approximately 28%), plasma levels of protein C decreased only in the E2+P group (approximately 4%) and plasma levels of protein S decreased in both the E2 and E2+P group (approximately 21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (approximately 10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (approximately 22%), urokinase plasminogen activator (approximately 25%) and plasminogen activator inhibitor type-1 (approximately 43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (approximately 12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (approximately 31%), but levels of thrombin-antithrombin III complexes, and of plasmin-alpha2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly. CONCLUSION: Short-term E2 and E2+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.

Blood Coagulation↗
PubMed2000

Radioimmunotherapy with intravenously administered 131I-labeled chimeric monoclonal antibody MOv18 in patients with ovarian cancer.

UNLABELLED: We investigated the safety and pharmacokinetics of (131)I-labeled chimeric monoclonal antibody MOv18 ((131)I-c-MOv18 IgG) in patients with ovarian cancer and the estimated radiation dose to cancer-free organs and tumor. METHODS: Three patients were injected intravenously with 3 GBq (131)I-c-MOv18. Toxicity was evaluated according to the World Health Organization toxicity scales. Blood sampling was performed for 12 wk after injection. Whole-body and SPECT imaging was performed frequently. Dose rates were obtained with a portable dose-rate measure. Quantitative activity analysis of several organs was performed with the region-of-interest technique. Absorbed doses were calculated using MIRDOSE3. RESULTS: Transient changes in hematologic profiles were seen in 2 patients. Pancytopenia developed in 1 patient; on analysis, she entered the study probably with exhausted bone marrow reserves. Nonhematologic toxicity was mild. No human antichimeric antibody responses were observed. Mean isolation time was 12 d. The plasma elimination half-life increased almost 3-fold compared with that after tracer doses of c-MOv18. Dosimetry showed mean absorbed doses of 163, 380, 276, 338, 781, and 216 cGy, for whole-body, liver, kidney, spleen, lung, and red marrow, respectively. Tumor-absorbed doses ranged from 600 to 3800 cGy. All patients achieved a stable disease state, as confirmed by CT and carcinoma-associated antigen CA 125, lasting from 2 to >6 mo. CONCLUSION: (131)I-labeled c-MOv18 can safely be given to patients with noncompromised bone marrow reserves and may have therapeutic potential particularly in patients with minimal residual disease.

Antibodies, Monoclonal↗
PubMed1999

Postmenopausal hormone replacement in the woman with a reproductive risk factor for breast cancer.

OBJECTIVE: to assess the interaction between postmenopausal hormone replacement therapy (HRT) and various reproductive risk factors for breast cancer such as early menarche, late menopause, late first delivery and nulliparity. DESIGN: three cohort studies and fourteen case control studies, published between 1975 and 1997, provided relative risks (RRs) of HRT use in women with, as well as in those without, a reproductive risk factor for breast cancer. METHODS: using an additive RR model reported before, we investigated whether the RR for breast cancer in women with a combination of HRT and a given reproductive risk factor result from a simple addition of RRs of HRT on the one hand, and of the pre-existing reproductive risk factor on the other hand, or that synergism between both risk factors occurs. RESULTS: simple addition of RRs was shown in the case of early menarche and late menopause. Less increase of risk, suggesting antagonism, was found for both late first delivery and nulliparity in combination with HRT use. CONCLUSION: we could not observe any synergistic effect of the combined risks of any of the following reproductive risk factors for breast cancer: early menarche, late menopause, late first delivery or nulliparity on the one hand, with the risk resulting from HRT use on the other hand. Therefore, as far as the risk of breast cancer is concerned, the use of HRT appears not to be highly detrimental in women with a reproductive breast cancer risk factor, as it results in not more than a simple addition of risks at the most.

Breast Neoplasms↗
PubMed1999

Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study.

BACKGROUND: A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening. METHODS: We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer. FINDINGS: 33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21-59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear. INTERPRETATION: Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Adolescent↗
PubMed1999

Hormone replacement therapy in women treated for gynaecological malignancy.

Can we prescribe hormone replacement therapy (HRT) safely for women, with postmenopausal complaints who were treated for a gynaecological malignancy? Only three retrospective studies have investigated this issue in endometrial cancer patients. No recurrences or deaths occurred in these treated groups. However, the physician introduced bias through the selection of favourable groups. At present, combined estrogen and progestogen therapy is probably not contra-indicated in endometrial cancer stage I and probably also not in stage II, although so far there is only circumstantial evidence. Squamous cell cancers of the cervix, vulva, and vagina are unlikely to be influenced by HRT. In the only study available of women with ovarian cancer, < or = 50 years, estrogen replacement therapy did not have a negative influence on (disease-free) survival. According to the data currently available, no evidence exists that HRT adversely influences survival and overall survival after treatment for ovarian cancer. In general, adenocarcinomas of the cervix and leiomyosarcomas of the uterus may be managed such as the adenocarcinomas of the uterus. During the last 25 years, HRT has been shown to substantially reduce the risk of cardiovascular diseases, osteoporotic fractures and colon carcinoma. On the other hand there is a significant increase of the risk in breast cancer with prolonged use of > 5 years. Re-evaluation of the current view that HRT should no be given to women treated for a gynaecological malignancy is strongly warranted after evaluating the advantages and the disadvantages of HRT use in each individual patient. Long-term HRT in women treated for a gynaecological cancer must be based on the medical history of the individual patient (and her family).

Contraindications↗
PubMed1999

Micturition complaints in postmenopausal women treated with continuously combined hormone replacement therapy: a prospective study.

OBJECTIVES: To study parameters of the micturition pattern in postmenopausal women and the effect of an oral continuously combined HRT-regimen. METHODS: Hormone therapy consisted of 2 mg 17 beta-oestradiol in combination with either 2.5, 5, 10 or 15 mg dydrogesterone, orally once a day. The baseline assessment was done just before starting hormone replacement therapy, the second assessment took place after 6 months of hormone therapy. Data were collected using a standardized questionnaire and focused on diurnal urinary frequency, nocturnal urinary frequency and urinary incontinence as parameters of the micturition pattern. Furthermore, bacteriuria was assessed. RESULTS: One hundred and two women entered the study and 95 women completed 6 months of hormone replacement therapy. Urinary incontinence was reported by 44.1% of the women, in 19.6% of the women it occurred more than twice a week. Both diurnal frequency and nocturnal frequency was reported by 28.4% of the women. For women with frequency or nocturia, the number of voids significantly decreased after 6 months hormone replacement therapy. Nocturia disappeared in 65.4% of the women after treatment and 23.3% reported to be cured of their urinary incontinence. Bacteriuria was present in the same seven women before and after hormone treatment. Dydrogesterone dose did not influence treatment outcomes. CONCLUSIONS: Postmenopausal women report improvement on urinary incontinence and nocturia after 6 months of a continuously combined hormone replacement therapy regimen. The improvement was most outspoken with regard to nocturia. Bacteriuria was not influenced. Different doses of dydrogesterone did not effect these findings.

Administration, Oral↗
PubMed1999

CA 125: fundamental and clinical aspects.

Since the OC 125 monoclonal antibody (Mab) was generated, other Mabs to the CA 125 glycoprotein have been produced and classified into two families associated with two major epitope regions on the CA 125 molecule. New generation assays, combining Mabs to two distinct regions of the molecule, compare favorably with that of the original assays as demonstrated by ROC curves. The original CA 125 assay suffered from interference of HAMA, an important drawback considering the increasing use of murine antibodies for immunodiagnosis and treatment of ovarian cancer. This problem has been solved for the majority of currently available tests. The sensitivity of the assays for early ovarian cancer remains low, precluding its indiscriminate use for screening and diagnosis of ovarian cancer. Its use in screening for early cancer, combined with ultrasonography, is limited to high risk populations, such as women from families with mutations in the BRCA1 or 2 gene. Although CA 125 assessment may play a limited role in the (early) detection of ovarian cancer, its role in the follow-up during and after therapy is well established. The major contribution of CA 125 is in the monitoring of tumor response to chemotherapy, where it is valuable in detecting those patients with an inadequate response to the chosen treatment. The role of CA 125 in early detection of recurrences remains to be established and is currently the subject of two large clinical trials.

Animals↗
PubMed1999

Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls.

The objective of this study was to demonstrate the presence of proliferative T cell responses to human polymorphic epithelial mucin (MUC1) and its tandem-repeat peptides in peripheral blood mononuclear cells (PBMC) from ovarian cancer patients and from controls and to correlate these cellular responses to a humoral response to MUC1. PBMC were obtained from 6 healthy women, from 13 women in the third trimester of pregnancy and from 21 ovarian cancer patients. Only 1 of the 6 healthy women showed a weak primary proliferative response (stimulation index, SI <2) to a 20-mer MUC1 tandem-repeat peptide in the presence of interleukin-2 (IL-2). In PBMC from 5/13 pregnant women (38%) a weak response could be induced by the 20-mer and/or 60-mer tandem-repeat peptides (SI < or =3.0) and in PBMC from 8/15 ovarian cancer patients (53%) 20-mer and/or 60-mer MUC1 tandem-repeat peptides induced primary responses (SI < or =5.4). MUC1 mucin purified from a breast tumor cell line and/or from urine of a healthy donor had a relatively strong stimulating effect (SI < or =19) on PBMC from 4 of 16 ovarian cancer patients (25%). In contrast, in PBMC of 9 ovarian cancer patients stimulated by the addition of a Candida albicans extract, MUC1 mucin strongly inhibited proliferation. This inhibition could partially be abrogated by the addition of IL-2. MUC1 (CA 15.3 assay) and free circulating MUC1 IgG and IgM antibodies (PEM.CIg assay) were determined in the plasma of all subjects. The MUC1 and the free circulating MUC1 IgG antibody plasma levels were significantly higher in the ovarian cancer patients than in the healthy women. Although no significant correlations were found between MUC1 mucin, MUC1 Ab plasma levels and the individual proliferative responses to the MUC1 antigens, an association may exist between them, since all three are significantly higher in the ovarian cancer patients than in the healthy women.

Amino Acid Sequence↗
PubMed1999

Sequentially combined hormone replacement therapy reduces impedance to flow within the uterine and central retinal arteries in healthy postmenopausal women.

OBJECTIVE: The purpose of this study was to investigate the long-term effects of combined hormone replacement therapy on the impedances of the uterine, central retinal, and ophthalmic arteries in healthy postmenopausal women. STUDY DESIGN: In a prospective controlled study we randomly assigned 30 healthy postmenopausal women (mean age, 52 +/- 3 years) to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and 2 mg 17beta-estradiol combined with 10 mg dydrogesterone thereafter for a period of 3 months. The control group (n = 15) received no treatment. Color Doppler ultrasonography was used to measure the impedance to flow (pulsatility index) within the uterine, central retinal, and ophthalmic arteries in the 17beta-estradiol phase at baseline and after 3, 12, and 15 months. RESULTS: With respect to values in the control group, 12 months of hormone replacement therapy was associated with a significantly lower (by 39%) mean pulsatility index of the uterine artery (decrease from baseline of 25% in hormone replacement therapy group and increase of 14% in control group) and a significantly lower (by 29%) mean pulsatility index of the central retinal artery (decrease of 9% in hormone replacement therapy group and increase of 20% in control group). After 3 months this effect was already evident. During hormone replacement therapy the reductions in mean pulsatility index values of the uterine and central retinal arteries with respect to baseline were larger (both P =.002) in the women with high pretreatment pulsatility index values than in those with low pretreatment values. The baseline pulsatility index of the uterine artery correlated positively with age and with duration of amenorrhea (r = 0.42, P =. 01; r = 0.48, P =.008; respectively). CONCLUSION: These results suggest that 12 months of sequentially combined hormone replacement therapy with a low dose of estradiol (1 mg) lowers arterial impedance in specific vascular territories. These data may help in understanding the effects of hormone replacement therapy on the cerebral circulation.

Drug Administration Schedule↗
PubMed1999

Long-term effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity in healthy postmenopausal women.

OBJECTIVE: To study the effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity. DESIGN: Prospective, randomized, controlled study. SETTING: Academic hospital. PATIENT(S): Healthy postmenopausal women with an intact uterus. INTERVENTION(S): For the first 12 months, the hormone replacement therapy group (n = 14) received oral E2, 1 mg daily, sequentially combined with 5 or 10 mg of dydrogesterone. Thereafter, they received oral E2, 2 mg daily, sequentially combined with 10 mg of dydrogesterone. The control group (n = 13) received no treatment. Data were collected at baseline and at 3, 12, and 15 months. MAIN OUTCOME MEASURE(S): Parameters of endothelial function and inflammatory activity. RESULT(S): During 12 months of follow-up, we observed decreases of 15% in plasma levels of endothelin-l, of 21% in soluble thrombomodulin, of 14% in von Willebrand factor, and of 12% in clottable fibrinogen in the hormone replacement therapy group compared with the control group. There was a 5% decrease in soluble E-selectin tevels. All significant changes were observed by 3 months and sustained after 15 months. Brachial artery flow-mediated vasodilatation and C-reactive protein levels did not change significantly. CONCLUSION(S): Long-term combined hormone replacement therapy with E2 and dydrogesterone in healthy women was associated with sustained improvement in some aspects of endothelial function and in clottable fibrinogen levels.

Dydrogesterone↗