Oral Hormone Replacement Therapy Research Articles

Hormone replacement therapy and the risk of venous thromboembolism: a population-based study.

Hormone replacement therapy (HRT) using oral estrogen alone or combined with a progestogen is associated with an increased risk of venous thromboembolism (VTE) in postmenopausal women. This risk may differ for tibolone and transdermal HRT. Among the United Kingdom's General Practice Research Database, we identified the cohort of all women aged 50-79 between 1 January 1987 and 1 March 2008. Using a nested case-control approach, all incident cases of VTE occurring during the study period were identified and matched with up to 10 controls selected from the cohort members. Rate ratios (RR) of VTE with current use of tibolone, transdermal and oral HRT were estimated using conditional logistic regression. The cohort of 955 582 postmenopausal women included 23 505 cases of VTE matched with 231 562 controls. The risk of VTE was not increased with current use of transdermal estrogen alone (RR 1.01; 95% CI, 0.89-1.16) or combined with a progestogen (RR 0.96; 95% CI, 0.77-1.20), or with current use of tibolone (RR 0.92; 95% CI: 0.77-1.10), relative to non-use. On the other hand, the risk was increased with current use of oral estrogen (RR 1.49; 95% CI, 1.37-1.63) and oral estrogen-progestogen (RR 1.54; 95% CI, 1.44-1.65), and increased with estrogen dosage. The risks with oral formulations were particularly elevated during the first year of use but disappeared 4 months after discontinuation. Transdermal HRT and tibolone were not associated with an increased risk of VTE in postmenopausal women.

Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study

Objectives To determine the risk of stroke associated with oral and transdermal routes of administration of hormone replacement therapy.Design Population based nested case-control study. Setting About 400 general practices in...

Comparative study of breast cancer in Mexican and Mexican-American women

Breast cancer is the number one cause of can- cer deaths among Hispanic women in the United States, and in Mexico, it recently became the primary cause of cancer deaths. This malign- nancy represents a poorly understood and un- derstudied disease in Hispanic women. The ELLA Binational Breast Cancer Study was es- tablished in 2006 as a multi-center study to as- sess patterns of breast tumor markers, clinical characteristics, and their risk factors in women of Mexican descent. We describe the design and implementation of the ELLA Study and provide a risk factor comparison between women in the U.S. and those in Mexico based on a sample of 765 patients (364 in the U.S. and 401 in Mexico). Compared to women in Mexico, U.S. women had significantly (p < 0.05) lower parity (3.2 vs. 3.9 mean live births) and breastfeeding rates (57.5% vs. 80.5%), higher use of oral contraceptives (60.7% vs. 50.1%) and hormone replacement therapy (23.3% vs. 7.6%), and higher family history of breast cancer (15.7% vs. 9.0%). Re- sults show that differences in breast cancer risk factor patterns exist between Mexico and U.S. women. We provide lessons learned from the conduct of our study. Binational studies are an important step in understanding disease pat- terns and etiology for women in both countries.

Obstructive prosthetic atrioventricular valve thrombosis in a woman with congenitally corrected transposition of the great arteries during estrogen replacement therapy for pituitary dysfunction

A 27-year-old woman was admitted because of breathlessness, orthopnea, and hemoptysis. The present patient was diagnosed with congenitally corrected transposition of the great arteries (cc-TGA) and underwent systemic atrioventricular valve replacement for severe insufficiency at 23 years of age. She also had been treated with oral conjugated equine estrogen (Premarin) because of congenital pituitary dysfunction. Despite appropriate anticoagulation therapy with warfarin, echocardiography and fluoroscopy showed stuck leaflets of the prosthetic valve due to thrombosis. She underwent emergent surgical valve replacement. This rare association suggests that oral hormone replacement therapy poses a risk of thrombosis especially in patients with cc-TGA after prosthetic valve replacement.

A severe case of ovarian hyperstimulation syndrome with pulmonary thromboembolism

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, life-threatening complication of ovarian stimulation. Renal and hepatic dysfunction, thrombosis, pulmonary edema, cerebral infarcts and adult respiratory distress syndrome are the leading causes of morbidity and mortality seen in severe cases. Here we report a case of OHSS with pulmonary thromboembolic event. Although the pathogenesis of thromboembolic events occurring during OHSS is not clear, it is probable that rising levels of estradiol may trigger hypercoagulability. Thromboembolic events seen with oral contraceptives and hormone replacement therapy support this hypothesis.

Can Colorectal Cancer be Prevented or Treated by Oral Hormone Replacement Therapy?

Guanylyl cyclase C (GCC) is the receptor specifically expressed by intestinal cells for the paracrine hormones guanylin and uroguanylin and diarrheagenic bacterial heat-stable enterotoxins. This tissue-specific receptor coordinates lineage-dependent regulation of epithelial homeostasis, and its disruption contributes to intestinal tumorigenesis. It coordinates regenerative and metabolic circuits by restricting the cell cycle and proliferation and programming metabolic transitions central to organizing the dynamic crypt-surface axis. Further, mice deficient in GCC signaling are more susceptible to colon cancer induced by Apc mutations or the carcinogen azoxymethane. Moreover, guanylin and uroguanylin are gene products most commonly lost, early, in colon cancer in animals and humans. The role of GCC as a tumor suppressing receptor regulating proliferation and metabolism, together with the universal loss of guanylin and uroguanylin in tumorigenesis, suggests a model in which colorectal cancer is a paracrine hormone deficiency syndrome. In that context, activation of GCC reverses the tumorigenic phenotype by limiting growth of colorectal cancer cells by restricting progression through the G1/S transition and reprogramming metabolic circuits from glycolysis to oxidative phosphorylation, limiting bioenergetic support for rapid proliferation. These observations suggest a pathophysiological hypothesis in which GCC is a lineage-dependent tumor suppressing receptor coordinating proliferative homeostasis whose dysregulation through hormone loss contributes to neoplasia. The correlative therapeutic hypothesis suggests that colorectal cancer is a disease of hormone insufficiency that can be prevented or treated by oral supplementation with GCC ligands.

Can Colorectal Cancer be Prevented or Treated by Oral Hormone Replacement Therapy?

Can Colorectal Cancer be Prevented or Treated by Oral Hormone Replacement Therapy?

Estrogen Receptor Polymorphisms: Significance to Human Physiology, Disease and Therapy

Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and (ERalpha and beta). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERalpha and ERbeta, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

Effects of hormone replacement therapy with vitamin C and E supplementation on plasma thyroid hormone levels in postmenopausal women with Type 2 diabetes

Recent studies have shown that hormone replacement therapy (HRT) can exert regulatory affects on lipid and glucose homeostasis. It has been demonstrated that hyperglycemia also involving the formation of lipid peroxides, exert several biological effects that may contribute to the onset and progression of thyroid and kidney abnormalities of postmenopausal women Type 2 diabetes. Therefore, the aim of our study was to evaluate the effect of HRT, vitamin C and E (VCE) treatments on some plasma biochemical and hematological parameters and plasma thyroid hormone levels in postmenopausal women with or without diabetes. Oral HRT and VCE supplementation were compared with no HRT treatment in 40 non-diabetic postmenopausal women and 40 postmenopausal women with Type 2 diabetes mellitus, in a 6-week randomized prospective study. In the 20 women with diabetes who received oral HRT and the 20 women with diabetes who received HRT plus VCE, there was a significant fall in urea, uric acid, creatinine, total bilirubin, conjugated bilirubin, AST, ALT, LDH values. There was no significant change in red blood cell counts, total protein, albumin, sodium, potassium, hematocrit, hemoglobin and free thyrotoxine and triiodothyronine values in postmenopausal women with diabetes or treated with oral HRT and VCE. In conclusion, daily VCE and HRT administrations seem to produce significant improvement on biochemical parameters in the blood of postmenopausal women with Type 2 diabetes. The HRT and VCE supplementations may strengthen the antioxidant defense system and they may play a role in preventing kidney and liver diseases of postmenopausal women with Type 2 diabetes.

Does use of estrogens decrease the Breslow thickness of melanoma of the skin? Oral contraceptives and hormonal replacement therapy

Recently, we showed there was a cumulative dose-dependent association between the use of estrogens and the incidence of cutaneous melanoma (CM). This association was shown for both oral contraceptives (OC) and hormonal replacement therapy (HRT). Some in-vitro studies, however, have suggested a direct inhibitory effect on melanoma tumor growth. Therefore, the use of different types of estrogens, OC and HRT, may be associated with a decreased Breslow thickness. Consequently, the clinical impact of our earlier findings may be limited. In this study, we investigated whether estrogen use (0.5 year), OC or HRT, is associated with a decreased Breslow thickness. For this study, we linked the national Dutch pathology database (PALGA) to a pharmacy database (PHARMO). Cases were women with a primary CM between 1 January 1991 and 14 December 2004, aged > or =18 years and having > or =3 years of follow-up before diagnosis of CM. In total, 687 women with melanoma were included. Univariable linear regression analysis suggested a decreased Breslow thickness with the use of OC and HRT. Statistically significant interaction was observed between age and estrogen use (P<0.01) suggesting effect modification by age. However, in stratified multivariable analyses for different age groups (<45, 45-55, > or =55 years), no statistically significant associations between the use of OC or HRT and Breslow thickness were observed. In conclusion, an association between use of OC and HRT and Breslow thickness could not be confirmed.

Effects of Oral Estrogen on Aortic ROS-Generating and -Scavenging Enzymes and Atherosclerosis in apoE-Deficient Mice

The effect of hormone replacement therapy (HRT) on cardiovascular diseases remains controversial. Studies conducted on postmenopausal women indicate that oral HRT increases risk factors that may counteract the atheroprotective effect of estrogen. However, the effects of estrogen on atherosclerosis have been examined using subcutaneous estrogen in most animal studies, which points to the need for evaluating the effect of oral estrogen. Reactive oxygen species (ROS) have emerged as critical factors in the pathogenesis of atherosclerosis. This study examined the effect of long-term oral estrogen treatment on aortic oxidative stress and atherosclerosis in female apoE(-/-) mice to mimic HRT in humans. Ovariectomized apoE(-/-) mice were given 6 microg/day of oral 17beta-estradiol (E(2)) or control vehicle for 12 weeks. Estrogen treatment reduced atherosclerotic lesions by 38% (E(2): 0.20 +/- 0.01 mm(2)/section; control vehicle: 0.32 +/- 0.02 mm(2)/section) and intima by 32% (E(2): 0.44 +/- 0.02 mm(2)/section; control vehicle: 0.65 +/- 0.04 mm(2)/section) in the aortic root. Serum levels of total and low-density lipoprotein cholesterol were significantly decreased after estrogen treatment. Aortic superoxide anion levels and the expression of NAD(P)H oxidase subunit p22(phox) markedly decreased, and two ROS scavenging enzymes, Cu/ZnSOD and MnSOD, were upregulated after estrogen treatment. Estrogen at physiological concentration inhibited tumor necrosis factor-alpha-stimulated NAD(P)H oxidase activity in both cultured smooth muscle cells and peritoneal macrophages. These results showed that long-term oral estrogen treatment reduces ROS levels and atherosclerosis progression in apoE(-/-) mice. Oral estrogen alters ROS-generating and -scavenging enzyme expression, suggesting that anti-oxidative actions in the vessel wall contribute to atheroprotective effects of estrogen.

Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer

Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency-related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.

Cerebral Venous and Sinus Thrombosis in Women

Little is known about the gender-specific manifestations of cerebral venous and sinus thrombosis, a disease that is much more common in women than men. We used data of the International Study on Cerebral Vein and Dural sinus Thrombosis (ISCVT), a multicenter prospective observational study, to analyze gender-specific differences in clinical presentation, etiology, and outcome of cerebral venous thrombosis. Four hundred sixty-five of a total of 624 patients were women (75%). Women were significantly younger, had less often a chronic onset of symptoms, and had more often headache at presentation. There were no gender differences in ancillary investigations or treatment. A gender-specific risk factor (oral contraceptives, pregnancy, puerperium, and hormonal replacement therapy) was present in 65% of women. Women had a better prognosis than men (complete recovery 81% versus 71%l P=0.01), which was entirely due to a better outcome in female patients with gender-specific risk factors. Women without gender-specific risk factors are similar to men in clinical presentation, risk factor profile, and outcome. Logistic regression analysis confirmed that the absence of gender-specific risk factors is a strong and independent predictor of poor outcome in women with sinus thrombosis (OR, 3.7; CI, 1.9 to 7.4). Our study identified important differences between women and men in presentation, course, and risk factors of cerebral venous and sinus thrombosis and showed that women with a gender-specific risk factor have a much better prognosis than other patients.

Occurence of venothromboembolism (VTE) in patients (pts) with acute lymphocytic leukemia (ALL), Burkitt's leukemia/lymphoma (BL), or lymphoblastic leukemia (LL)

7059 Background: Venous thromboembolism (VTE) is a significant public health issue. Although neoplastic diseases are known risk factors for the development of VTE, little is known about the incidence and predisposing factors of VTE among leukemia patients (pts). Methods: We performed a retrospective study to determine the incidence and risk factors associated with development of VTE among pts with ALL, BL, LL at M. D. Anderson Cancer Center between 1999 and 2005. Medical records of 299 ALL pts were reviewed and analyzed. All computations were conducted using Stata 10. Results: Of the 299 pts with a male/female ratio of 182/117 and a median age of 43 yrs (range 15–83 yrs), 18% had VTE. Recurrent VTE occurred in 10 pts. VTE were identified in upper extremities (59%), lower extremities (30%), pulmonary vasculature (7%), and within venous catheters (4%). In a univariate model, pts with baseline platelet (plt) count 50–99 x 109/L were 2.2 times (95% CI: 1.05–4.55) more likely to develop VTE than pts who had plt &gt;100 x 109/L. Pts aged 40–59 yrs were 2.3 times (95% CI: 1.15–4.59) more likely to develop VTE than pts aged 15–39 yrs. Women were 1.8 times (95%CI: 1.04–3.4) more likely than men to have a VTE. Pts with a history of VTE were 15.2 times (95% CI: 2.97–77.51) more likely to develop a VTE than pts who had no prior VTE history. Pts with &gt; 3 comorbidities were 2.6 times (95% CI: 1.19–5.48) more likely to develop VTE than pts without comorbidities. Pts who used oral contraception or hormone replacement therapy (OCP/HRT) were 2 times (95% CI: 1.07–3.92) more likely to develop VTE than non-users. Pts with Philadelphia chromosome (Ph)-positive ALL were 3 times (95%CI: 1.41–6.17) more likely to develop VTE than pts with Ph-negative ALL. In a multivariate model, significant predictors of VTE were age 40–59 yrs, plt count 50–99 x 109/L, diagnosis of Ph-positive ALL, history of VTE, and OCP/HRT use. Conclusions: Pts with ALL have a high VTE rate. In addition to traditional risk factors, disease-specific features may also predispose pts to higher VTE risk. Further studies should be done in other leukemias to establish guidelines in the prevention and management of VTE in pts with leukemia. [Table: see text]

Evidence-based review of therapies at the menopause

Background and Objective The highest level of scientific evidence available for each therapy for menopausal symptoms was sought, for example, systematic reviews of randomised controlled trials (RCTs). Results There is reasonable evidence that some symptoms are modified by lifestyle, for example, cessation of smoking, exercise, reduction of alcohol, diet and alleviation of psychosocial stress. No complementary medicine, for example, phytoestrogens, black cohosh, herbal or homeopathic medicines or complementary therapies, for example, acupuncture, yoga, chiropractic manipulation, reflexology or magnetic devices have a greater effect than the usual placebo effect seen in quality blinded RCTs. Some have potential side-effects. So-called 'bioidentical hormones' have no evidence-base and potential for harm. None of the above therapies have evidence of efficacy and long-term safety. Selective serotonin and noradrenaline re-uptake inhibitors ameliorate vasomotor symptoms and sometimes menopausal depression better than placebo. The most effective therapy for menopausal (oestrogen) deficiency symptoms is oestrogen which is the main component of hormone replacement therapies (HRT). Compared with placebo HRT is highly effective in relieving hot flushes, night sweats, dry vagina and dyspareunia. It also improved joint pains, sexuality and sleeplessness and reduced subsequent fractures in RCTs. The increased risk of oral HRT for thromboembolism is small around menopause, for those without thrombotic risk factors, and is not elevated with non-oral routes. Cardiovascular disease may be reduced when HRT is initiated near menopause. Breast cancer risk increases after several years with the use of oral HRT containing progestogens at an annual rate of 8/10 000 (<0.1%). No increase in breast cancer risk was seen with oestrogen-only HRT.

Risk Factors for Pituitary Tumors: A Case-control Study

Pituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential risk factors for pituitary tumors in Southeast England. Information on medical and reproductive history, female sex hormones, and cigarette smoking was collected by personal interview from 299 cases and 630 controls aged 18 to 59 years. Tumor risk was reduced in subjects reporting a past diagnosis of hay fever [odds ratio (OR), 0.7; 95% confidence interval (CI), 0.5-1.0] but not asthma or eczema. Risk was raised in women who were postmenopausal 1 year before diagnosis (OR, 3.2; 95% CI, 1.6-6.2), especially if menopause was surgically induced (OR, 6.7; 95% CI, 2.2-19.9) or occurred under age 40 years (OR, 7.5; 95% CI, 2.6-21.4). This effect remained when evaluating menopausal status 10 years before diagnosis. There was no association with parity overall, but risk was increased for first childbirth under age 20 years compared with nulliparity (OR, 3.4; 95% CI, 1.4-8.4). No significant association was observed with ever use of oral contraceptives or hormone replacement therapy, nor with cigarette smoking, past head injury, past diagnosis with epilepsy, or birth characteristics, except for an inverse association of risk with maternal age. This study suggests a raised risk of pituitary tumors in relation to surgically induced menopause, early postmenopausal age, and young age at childbirth, and possibly a reduced risk with hay fever and increasing maternal age. Reasons for these associations need further investigation, but some associations might be due to hormonal effects of an undiagnosed pituitary tumor.

Differences in reproductive risk factors for breast cancer in middle-aged women in Marin County, California and a sociodemographically similar area of Northern California

BackgroundThe Northern California county of Marin (MC) has historically had high breast cancer incidence rates. Because of MC's high socioeconomic status (SES) and racial homogeneity (non-Hispanic White), it has been difficult to assess whether these elevated rates result from a combination of established risk factors or other behavioral or environmental factors. This survey was designed to compare potential breast cancer risks and incidence rates for a sample of middle-aged MC women with those of a demographically similar population.MethodsA random sample of 1500 middle-aged female members of a large Northern California health plan, half from Marin County (MC) and half from a comparison area in East/Central Contra Costa County (ECCC), were mailed a survey covering family history, reproductive history, use of oral contraceptives (OC) and hormone replacement therapy (HRT), behavioral health risks, recency of breast screening, and demographic characteristics. Weighted data were used to compare prevalence of individual breast cancer risk factors and Gail scores. Age-adjusted cumulative breast cancer incidence rates (2000–2004) were also calculated for female health plan members aged 40–64 residing in the two geographic areas.ResultsSurvey response was 57.1% (n = 427) and 47.9% (n = 359) for MC and ECCC samples, respectively. Women in the two areas were similar in SES, race, obesity, exercise frequency, current smoking, ever use of OCs and HRT, age at onset of menarche, high mammography rates, family history of breast cancer, and Gail scores. However, MC women were significantly more likely than ECCC women to be former smokers (43.6% vs. 31.2%), have Ashkenazi Jewish heritage (12.8% vs. 7.1%), have no live births before age 30 (52.7% vs. 40.8%), and be nulliparous (29.2% vs. 15.4%), and less likely to never or rarely consume alcohol (34.4% vs. 41.9%). MC and ECCC women had comparable 2000–2004 invasive breast cancer incidence rates.ConclusionThe effects of reproductive risks factors, Ashkenazi Jewish heritage, smoking history, and alcohol consumption with regard to breast cancer risk in Marin County should be further evaluated. When possible, future comparisons of breast cancer incidence rates between regions should adjust for differences in income and education in addition to age and race/ethnicity, preferably by using a sociodemographically similar comparison group.

Different estrogen sensitivity of urogenital tissue from women with and without stress urinary incontinence

Oral hormone replacement therapy (HRT) based on estradiol-17beta (E2), E2 esters or conjugated equine estrogens gives rise to huge amounts of circulating estrone (E1) as a result of the first liver pass. E1 is an estrogen (ER) receptor agonist but has also been reported to act as a partial E2 antagonist in vitro. Our aim was to investigate the influence of circulating estrogens on estrogen sensitivity of urogenital tissue collagen turnover in patients with stress urinary incontinence (SUI) and in urologically healthy women, with and without HRT, in view of possible effects of E1 as a partial E2 antagonist. Markers of collagen turnover, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and E1 and E2 were analyzed in serum from 54 patients with SUI and 29 urologically healthy women. In the total control group only a significant positive correlation was found between E2 and T-PICP. Lowering the upper serum E1 limit resulted in significant positive correlations also between E2 and T-PIIINP and finally also between E2 and T-ICTP. This pattern was found also in subgroups of post- and premenopausal controls. No association between serum E2 and collagen turnover markers and no effects of lowering the upper serum E1 limit was found in the total and postmenopausal SUI patients, while the correlation pattern in premenopausal SUI patients showed some resemblance to that in the controls. At physiological E1 levels E2 increases collagen turnover in urogenital tissue in urologically healthy women but not in women with SUI in general; however, there was a certain effect of E2 in premenopausal but not in postmenopausal SUI patients. Urogenital tissue in SUI patients and in urologically healthy women may differ in estrogen sensitivty and in SUI patients this difference may be related to menopause. Circulating E1, which is present in huge amounts during oral HRT, may act as an estrogen receptor agonist as well as a partial E2 antagonist also in humans in vivo.

The benefits of oestrogen following menopause: why hormone replacement therapy should be offered to postmenopausal women

Recently, two major epidemiological studies found that hormone replacement therapy (HRT) in postmenopausal women increased the risk of breast cancer. One of the studies also found that HRT increased the risk of cardiovascular disease and thrombosis. As a consequence, women were advised to cease this therapy. However, detailed analysis of these studies suggests that the conclusions may be erroneous. Other studies suggest that the timing of initiation of HRT for healthy women is critical to achieving a beneficial outcome. When begun within 5 years of menopause in healthy women, oestrogen-based HRT results in far greater benefits than adverse outcomes. There is substantial objective evidence that the benefits of HRT include: Reduced distressing symptoms of menopause. Reduced risk of osteoporotic fractures, dementia and colorectal cancer. Improved wellbeing, quality of life; improved vaginal epithelium, sexual enjoyment and bladder capacity. Improved cardiovascular system, with reduced myocardial ischaemia and cardiovascular-related death. Increased longevity. The adverse effects of HRT include: Oral HRT doubles the risk of thromboembolism. HRT promotes growth of pre-existing breast cancer.

Anticipating the anti-ageing pill. Lessons from the history of the oral contraceptive pill and hormone replacement therapy.

Throughout history, the prospect of extending the human lifespan—with the ultimate aim of living forever—has been an attractive fantasy. Now, some researchers argue that it will soon be possible to increase our average life expectancy to at least 100 years, if not more, by slowing down the processes of ageing (Guarente & Kenyon, 2000). There are several potential methods for life extension interventions (Lucke & Hall, 2006), but perhaps the most likely is an anti‐ageing pill, possibly one that mimics the well‐described, life‐extending effects of caloric restriction (Everitt & Le Couteur, 2007; Michalow, 2008). Let us assume, for the purpose of argument, that a pill could be developed in the next couple of decades that extended the average human lifespan to around 150 years. > Cultural values have an important influence on the acceptability of innovations… The development and distribution of an effective anti‐ageing pill would have significant societal impacts that could easily catch many parties unawares, including governments, medical practitioners and legislators. A useful way to anticipate what these impacts might be is to look at the history of two other innovations that profoundly changed society: the oral contraceptive pill (OCP; Asbell, 1995; Marks, 2001; Tone, 2001; Watkins, 1998) and hormone replacement therapy (HRT; Watkins, 2007). Such analogies are a useful tool for the bioethical analysis of new technologies (Hofmann et al , 2006) and therefore we propose to address the issue of human life extension by applying this approach. Since its creation more than 50 years ago, the OCP has been heralded as one of the “greatest miracle drugs” (Goldin & Katz, 2002), a “medical milestone” (Djerassi, 2007) and the first “lifestyle and designer drug” (Junod & Marks, 2002). It was the first virtually fail‐safe contraceptive method that women could use independently, and was controversial as …