Menopausal Therapy Research Articles

High C‐reactive protein levels are associated with oral hormonal menopausal therapy but not with intrauterine levonorgestrel and transdermal estradiol

Objective. Oral hormone replacement therapy (HRT) has been linked to increased cardiovascular (CVD) morbidity. HRT causes a sustained increase in C‐reactive protein (CRP), an excellent marker of subclinical inflammation and CVD. The aim of the study was to support our hypothesis that CRP, which is synthesized in the liver, is not increased in association with transdermal/intrauterine HRT. Material and methods. A case‐control study was performed in which CRP measurements in women receiving levonorgestrel intrauterine system combined with transdermal estradiol (LNG/TDE, n = 27) were followed for 9 months or longer. CRP concentrations in these women were compared with those of either oral HRT users (n = 20) or controls (n = 19). Results. No significant differences were found in CRP concentrations between the LGN/TDE and control groups (1.8±1.2 and 1.8±1.8 mg/L, respectively). However, CRP was significantly increased in the oral HRT group (5.5±2.9 mg/L, p<0.001). Conclusions. CRP is significantly increased by oral HRT but not by the LNG/TDE combination after 9 months of treatment. This trend may explain the preponderance of some menopausal women on HRT being at increased risk for the development of CVD. Therefore, the use of LNG/TDE is acceptable for relief of severe climacteric symptoms possibly not imposing an increased CVD risk documented upon oral HRT.

Safety and Security of Menopausal Therapies

Safety and Security of Menopausal Therapies

Safety and Security of Menopausal Therapies

Safety and Security of Menopausal Therapies

Estrogen–progestogen replacement therapy and ovarian cancer: an update

Hormone replacement therapy in menopause has been associated with a moderate increase in ovarian cancer risk. Data on combined estrogen-progestin therapy, based on one randomized trial, two cohort and four case-control studies, do not provide definite evidence of an association between combined hormone replacement therapy and ovarian cancer. These data do not suggest, however, substantial differences between the effect of estrogen only or unspecified hormone replacement therapy and combined hormone replacement therapy on ovarian cancer risk.

Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis

Little information is available on how the risk of breast cancer associated with the use of hormone therapy for menopause varies by histological type. We aimed to describe such associations for eight histological types of breast cancer. Analyses are based on 1 031 224 postmenopausal women recruited in 1996-2001 into a nationwide UK cohort study, and followed for incident cancer and death. Relative risks associated with use of hormone therapy were estimated for eight histological types of breast cancer. During 3.6 million person-years of follow-up, 14 102 breast cancers were diagnosed, of which 13 782 (98%) had histological type recorded: 11 869 (86%) were invasive, including 8007 ductal, 1526 lobular, 365 mixed ductal-lobular, 492 tubular, 71 medullary, and 148 mucinous cancers; and 1913 (14%) were in situ, including 1443 ductal and 86 lobular cancers. The relative risks of invasive breast cancer in current users compared with never users of hormone therapy varied significantly according to tumour histology overall (p<0.0001), for users of oestrogen-only therapy (p=0.0001), and for users of oestrogen-progestagen therapy (p<0.0001). The largest relative risks in current compared with never users of hormone therapy were seen for lobular (relative risk 2.25, 95% CI 2.00-2.52), mixed ductal-lobular (2.13, 1.68-2.70), and tubular cancers (2.66, 2.16-3.28). The relative risks for ductal and mucinous cancers were 1.63 (95% CI 1.55-1.72) and 1.58 (1.08-2.31), respectively. The risk of medullary cancer was not increased (0.74, 0.43-1.28). The relative risk of in-situ disease in current users compared with never users of hormone therapy also varied significantly according to histological type (p=0.03), with a relative risk for lobular carcinoma in situ of 2.82 (1.72-4.63) and 1.56 (1.38-1.75) for ductal carcinoma in situ. The effects of hormone therapy on invasive ductal, lobular, and tubular cancer were generally greater for oestrogen-progestagen therapy than for oestrogen-only therapy, and were attenuated with increasing body-mass index (BMI). The risks associated with use of hormone therapy for menopause differ by histological type of breast cancer, and are substantially attenuated with increasing BMI.

Hormonal Therapy: Does It Increase or Decrease Cardiovascular Risk?

The use of hormonal therapy (HT) has become one of the most controversial topics in the area of women's health. A particular area of confusion has been the issue of cardiovascular benefit versus cardiovascular risk for women using HT. Although years of observational data have suggested that women receiving HT have a lower incidence of coronary artery disease (CAD) and longer survival, several prospective, randomized controlled trials have brought this tenet into debate. This article provides a historical perspective on the role of HT and CAD. The Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative (WHI) data are analyzed in conjunction with newer data. Finally, an explanation will be provided as to how early initiation of HT could afford cardiovascular protection and not contradict the HERS and WHI. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader should be able to state that controversy still remains in the use of hormonal therapy (HT) for menopause, explain that there are conflicting data from both prospective and observational studies, and recall that a new look at prospective data may indicate that HT has beneficial cardiovascular effects.

Healthy Women with a Family History of Breast Cancer: Impact of a Tailored Genetic Counseling Intervention on Risk Perception, Knowledge, and Menopausal Therapy Decision Making

Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy (HT), alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision making in a group of healthy women who had a first-degree relative with breast cancer. Forty-eight cancer-free menopausal women age > or =40 years who had at least one first-degree relative with breast cancer were randomized to a genetic counseling intervention or control. Intervention participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. Knowledge, risk perception, and medication usage were measured at baseline, 1 month, and 6 months. Knowledge was higher in the intervention group at both follow-up time points postintervention. Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline, as was perceived risk of developing heart disease. Although the counseling intervention did affect both knowledge and risk perception, overall, both groups were reluctant to take any form of menopausal therapy. A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception; however, it is unclear that the intervention influenced menopausal treatment decisions.

Hormone replacement therapy in menopause and lung cancer: an update

Hormone replacement therapy in menopause and lung cancer: an update

Does teriparatide given in combination with menopausal hormone replacement therapy improve bone mineral density?

Does teriparatide given in combination with menopausal hormone replacement therapy improve bone mineral density?

Influence of menopausal status and use of hormone replacement therapy on radiation dose from mammography in routine breast screening

Menopausal status and hormone replacement therapy (HRT) cause alterations in breast structure which can affect mammographic image quality. Here we present the results of a study to discover the effect of menopausal status and HRT use on breast dose. Women attending routine screening completed questionnaires which included questions regarding menopausal status and HRT use. Details of the radiographic technique factors were recorded, from which the mean glandular dose (MGD) per film for each woman was calculated. MGD values were analysed with regard to the woman's menopausal status and HRT use. The data from 516 women were analysed. Among the women who had never used HRT, women who had not undergone the menopause had a mean MGD of 2.94 mGy per film, whereas post-menopausal women had a lower mean MGD of 2.52 mGy per film: a difference which was found to be highly significant (p = 0.0045). Post-menopausal women who had never used HRT and those who had previously used HRT, but had ceased using it, had identical mean MGDs (2.54 mGy per film), whereas current HRT users had a significantly greater mean MGD (2.89 mGy per film, p = 0.003). Women currently using HRT receive a statistically significantly larger radiation dose from routine breast screening than other women. However, this effect is small and only occurs during the period of HRT use. Women who have ceased using HRT show no difference in MGD compared with women who have never taken HRT.

Hormone replacement therapy in menopause and lung cancer: an update

Hormone replacement therapy in menopause and lung cancer: an update

Alternative Menopausal Therapies and Bone Health During the Menopausal Transition

Alternative Menopausal Therapies and Bone Health During the Menopausal Transition

Effects of Hormone Replacement Therapy Type and Route of Administration on Plasma Matrix Metalloproteinases and Their Tissue Inhibitors in Postmenopausal Women

Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy. A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods. MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05). Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.

Lean mass plays a gender-specific role in familial resemblance for femoral neck bone mineral density in adult subjects

Whether the femoral neck bone mineral density (FN BMD) of children may be better predicted from that of their parents when taking into account the anthropometry of the children was assessed in a healthy adult sample consisting of 86 mother-daughter, 32 mother-son, 32 father-daughter, and 23 father-son pairs from 128 families. Heritability for FN BMD, which is considered to be a measurement of general resemblance, was defined as the regression coefficient of the mean of the parents' BMD. Among the anthropometric factors, lean mass was the most strongly associated with FN BMD following the adjustment for age in women (r=0.52, p<0.0001) and men (r=0.25, p=0.02). After adjustment for age, calcium intake, physical activity, and menopause and hormonal replacement therapy if relevant, heritability estimates (h2) for FN BMD were 0.68+/-0.23 [95% credible interval (CI): 0.15-0.99] in father-daughter pairs, 0.40+/-0.17 (95% CI: 0.08-0.74) in mother-daughter pairs, and 0.19+/-0.15 (95% CI: 0.01-0.57) in father-son pairs. Adjustment for lean mass of children increased the h2 for FN BMD in mother-son pairs [from 0.24+/-0.17 (95% CI: 0.01-0.57) to 0.66+/-0.18 (95% CI: 0.26-0.95)]. The present results show that FN BMD is heritable in adult father-daughter pairs (7.2% of a daughter's FN BMD variance was explained by the father's FN BMD) and that taking into account the lean mass of sons might improve the prediction of their FN BMD based on that of their mother's (reduction of sons' FN BMD residual variance by 5.1%). Taking the lean mass of children into account might improve the prediction of their FN BMD by 9.1% in daughters and by 18.1% in sons, irrespective of their parent's FN BMD. These results, obtained using a Bayesian regression model, have to be confirmed in further studies involving a greater number of adult parent-offspring pairs of both genders before extrapolation to clinical practice.

The dilemma of menopause and hormone replacement – a challenge for women and health-care providers: knowledge of menopause and hormone therapy in Spanish menopausal women

Background An important goal in menopause research is to develop knowledge and identify interventions that strive to promote, maintain and enhance well-being for women.Objective To evaluate the knowledge of postmenopausal Spanish women about menopause and their knowledge of and trust in hormone replacement therapy (HRT) and to identify their sources of information and how those data are related to compliance with their prescription.Study design A total of 270 symptomatic postmenopausal women were personally interviewed using a structured questionnaire, which was designed to collect information on their familiarity with medical menopause studies, the menopause and the effects of HRT, their knowledge of alternative therapies, and to identify their sources of information.Results The most well-known menopausal complaints were hot flushes, sweats, irregular menstruation, cessation of menstruation, irritability and mood changes. Following suggestions of other symptoms by the interviewer, other complaints such as vaginal dryness, insomnia and depression/anxiety were also mentioned. HRT and phytoestrogens were recognized as treatments for the climacteric by most of the women. A woman's decision to seek treatment was initiated in 77% of cases by the gynecologist, in 12% by the general practitioner, in 3% by friends/family and in 3% by books/magazines. The most frequent responses of women to the onset of menopausal symptoms were to talk with their partner (39%), to discuss it with their gynecologist (33%) or with their general practitioner (14%) and to talk with their friends/family or to read books/magazines (10%).Conclusions Vasomotor symptoms are recognized as the main complaint during the climacteric and HRT and phytoestrogens as the main therapies. Gynecologists play an important role in assuring compliance with therapies related to the menopause.

Enhanced Growth of Hepatic Hemangiomatosis in Two Adults after Postmenopausal Estrogen Replacement Therapy

Liver hemangiomatosis is defined as extensive hemangioma in the liver. Although hemangioma is the most common hepatic tumor, diffuse hepatic hemangiomatosis is very rare. Most cases of hepatic hemangiomatosis are seen in infancy, but it is extremely rare in adults. This is the first report, showing the enhanced growth of diffuse hepatic hemangiomatosis after hormone replacement therapy. We report herein two unrelated women, 47 and 42 year-old, from different regions of Turkey, who admitted to hospital because of right abdominal pain with diffuse hepatic hemangiomatosis, developed after hormone replacement therapy for menopause. The patients were healthy, except for hemangiomatosis, and their physical examination, routine laboratory tests, and tumor marker levels were within normal limits. It should be noted that their abdominal ultrasonography was normal before hormone therapy, but ultrasonography on admission revealed numerous, ill defined, diffusely located liver nodules in both patients. Dynamic magnetic resonance imaging and scintigraphy have revealed that these lesions are compatible with hemangiomatosis. These results suggest that hepatic hemangiomatosis was induced by estrogen therapy. Consequently, hormone replacement therapy was discontinued, and the patients were followed up for 3 years. Their physical examination and blood chemistry, including liver enzymes, remained within normal range, and the follow-up examination with ultrasonography showed no changes in size of lesions. Because of the possible association of hemangioma with estrogen administration, decisions should be made carefully about estrogen therapy for patients who already have hemangioma, and the periodic ultrasonograpy examination should be planned to detect possible new growth of liver hemangiomatosis.

Effect of different preparations of hormone therapy on sexual dysfunction in naturally postmenopausal women

Objective To compare the effect of different formulations of continuous combined hormone therapy on sexual performance in naturally postmenopausal women.Material and methods A total of 158 postmenopausal women were enrolled and prospectively randomized to the single-blind study. Fifty-four women received tibolone 2.5 mg, 53 received 2 mg estradiol and 2 mg dienogest (E2/dienogest), and 51 did not receive any menopausal therapy. The patients were monitored after 6 months. Attitudes of sexuality were evaluated by using the Rosen's female sexual function index.Results Compared with E2/dienogest and the control group, tibolone treatment was associated with more improvement of sexual performance, including sexual desire, sexual arousal and satisfaction. Both of the hormone therapies decreased frequencies of vaginal dryness and painful intercourse.Conclusions Tibolone has more positive effects on the sexual dysfunction of postmenopausal women and may be an alternative to the E2/dienogest preparation in postmenopausal women with sexual dysfunction.

New Selective Tissue Estrogenic Activity Regulator (STEAR) in Menopausal Therapy in Taiwan

Summary Objective The compliance of women living in Taiwan with the selective tissue estrogenic activity regulator (STEAR) tibolone has seldom been reported. The purpose of this study was to evaluate the short-term compliance of perimenopausal women living in Taiwan in taking tibolone, and the efficacy of the drug. Materials and Methods A total of 289 perimenopausal women who had experienced mild to severe climacteric symptoms were enrolled in this study. Every woman was evaluated before (baseline), during (end of the third month), and after therapy (end of the sixth month) with 2.5 mg tibolone daily. Efficacy was assessed from improvement in climacteric symptoms and compliance was also assessed. Results A total of 275 women were still on tibolone treatment by the end of the study, revealing a high rate (95.2%) of retention. Breast tenderness was significantly reduced, from 26.5% to 2.8%. The reported rate of insomnia was 50.5% at baseline, and had been reduced to 20.4% by the end of the study. Bleeding episodes dropped from 87.4% at baseline to 39.4% at the end of the study. The rate of mood instability was significantly reduced, from 84.1% at baseline to 44.3% at the end of the study. Libido improved from 15.9% at baseline to 61.6% at the end of the study, a unique benefit of tibolone due to the androgenic effect of its d-isomer. Most women (84.1%) had an increase in body weight ranging from 0.5 to 3 kg. Fourteen subjects dropped out for the following reasons: three women had acne and/or allergic reaction, four had a significant increase in body weight and/or water retention, one had headache, and the other six dropped out for personal reasons. Conclusion Tibolone can improve the climacteric symptoms of perimenopausal women living in Taiwan. With the exception of increased body weight, no major side-effect was noted during this short-term study.

Assessment of Estrogen Status as a Marker of Prognosis in Women With Symptoms of Suspected Coronary Artery Disease Presenting for Stress Testing

Estrogen status (ES) has previously been shown to be a marker of angiographic outcome in women. In light of this finding, a reevaluation of ES as a marker of prognosis was undertaken. Two thousand one hundred forty-three women who underwent stress testing for symptoms of suspected coronary disease were studied. ES was defined according to menopausal, ovarian, and hormone replacement therapy status. The end points of interest were all-cause mortality, cardiac death, and nonfatal myocardial infarction. Survival analysis was performed using the Kaplan-Meier method and Cox regression analysis with censoring at revascularization. Compared with 1,362 ES-positive women, the 781 ES-negative women had a higher frequency of unfavorable end points (all-cause death: ES positive 31 [2.3%] vs ES negative 94 [12%], p < 0.0001, cardiac death: ES positive 11 [0.8%] vs ES negative 38 [4.9%], p < 0.0001, and nonfatal myocardial infarction: ES positive 11 [0.8%] vs ES negative 17 [2.2%], p = 0.007). The Kaplan-Meier curve analysis indicated that ES was a marker of cardiac risk (p < 0.0001) in all women, as well as in postmenopausal women. Multivariate Cox regression analysis revealed that ES was an independent marker of risk (p < 0.001) when considered with other standard risk factors. Using logistic regression and area under the curve analyses, ES had incremental value compared with standard risk factors. In conclusion, ES appears to be an easily discernible independent marker of risk that provides incremental prognostic information compared with standard clinical variables in women with symptoms of suspected coronary disease presenting for stress testing.

Effect of different preparations of hormone therapy on lipid and glucose metabolism, coagulation factors, and bone mineral density in overweight and obese postmenopausal women

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. A randomized, nonblinded, controlled study. Karadeniz Technical University, Department of Obstetrics and Gynecology. A total of 352 overweight and obese (body mass index >25 kg/m2) postmenopausal women. 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). 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. 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. 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.