Do menopausal hot flashes have any significant effects on arterial blood gas measurements?

Objectives: To evaluate the effects of menopausal hot flashes on arterial blood gas measurements. Methods: Twelve postmenopausal women with frequent hot flashes were enrolled in this study. Blood samples from femoral artery were collected before and during menopausal hot flashes in each subject, and all blood samples were analyzed for pH, pCO₂, pO₂, HCO₃ standard, total CO₂, and base excess. Arterial blood gas parameters before and during menopausal hot flashes were compared statistically. Results: pH measurements decreased significantly during hot flashes (P<0.05); although the difference was found to be statistically significant, the amount of decrease and the range in which the change took place led us to conclude that this change was clinically insignificant. Other parameters did not show any statistically significant differences between the preflash and flash measurements. Conclusions: Our results indicate that menopausal hot flashes do not have any clinically significant effects on arterial blood gas measurements.     

Differential factors associated with hot flashes in Chinese perimenopausal and postmenopausal women

Objective

This study investigated factors associated with hot flashes in Chinese perimenopausal and postmenopausal women.

Methods

This cross-sectional study recruited Chinese women aged 40–60 years who were perimenopausal or postmenopausal and examined factors associated with hot flashes. Participants completed a questionnaire detailing demographic information, characteristics of menstruation, reproductive history, use of hormone replacement therapy or oral contraceptives, personal lifestyle factors (exercise, multivitamin use, soy products use, diet), and symptoms of hot flashes. Height, weight, blood pressure, and waist and hip circumference were also measured.

Results

A total of 1399 participants (817 perimenopausal women and 582 postmenopausal women) completed the study. In perimenopausal women, college or higher education decreased the prevalence of hot flashes (odds ratio (OR) 0.63; 95% confidence interval (CI) 0.46–0.86). In postmenopausal women, an omnivorous diet decreased the prevalence of hot flashes (OR 0.38; 95% CI 0.17–0.85). Strenuous exercise (≥3 times a week) increased the prevalence of hot flashes (OR 1.41; 95% CI 1.08–1.83) in perimenopausal women.

Conclusions

It is possible that modifiable risk factors for hot flashes exist in Chinese perimenopausal and postmenopausal women. Future studies with larger populations are needed to confirm these findings.     

A comparative study of menopausal hot flashes and their psychosocial correlates in Taiwan and the United States

Objective

To compare the frequency, severity, and interference of menopause-related hot flashes and their psychosocial correlates in Taiwanese and U.S. women.

Study design

Cross-sectional study, using a convenience sample of 101 Taiwanese and 121 U.S. midlife women.

Main outcome measures

Hot-flash measures, including frequency, severity (Women's Health Initiative Symptom Scale), hot flash related daily interference; and psychosocial measures: Attitudes toward Menopause and Aging Scale, Coping Strategies Questionnaire, Sense of Coherence Questionnaire, Center for Epidemiological Studies-Depression Scale, Spielberger State-Trait Anxiety Inventory, and State-Trait Anger Scale.

Results

Using ANCOVA with demographic variables as covariates, U.S. women reported greater frequency and daily interference from hot flashes compared with Taiwanese women. Greater depression, greater catastrophizing about hot flashes, lower sense of coherence, lower state/trait anger, and more positive attitudes toward aging were reported in the U.S. cohort. The groups were similar in their frequency of specific coping strategies, and they did not differ significantly in menopause symptom severity, attitudes towards menopause, state/trait anxiety, or overall negative psychosocial characteristics. Hierarchical multiple regression analyses indicated that hot-flash related daily interference was predicted by marital status, frequency of hot flashes, and negative psychosocial characteristics among the U.S. women; and by frequency of hot flashes and negative psychosocial characteristics among the Taiwanese women.

Conclusions

Despite differences in the frequency and daily interference from hot flashes in the two samples, the predictors of interference were similar. Results highlight the importance of considering both psychosocial factors and cultural differences in providing guidance and treatment for women experiencing menopause-related hot flashes.     

Postmenopausal testosterone therapy and breast cancer risk

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen–progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. Design: Literature review. Setting: The Jean Hailes Foundation, Research Unit. Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer. Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. Conclusion: Available data indicate the inclusion of testosterone in estrogen–progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.     

The incidence of breast cancer and changes in the use of hormone replacement therapy: A review of the evidence

Even though a link between hormone replacement therapy (HRT) and breast cancer has been well documented in the epidemiological literature since the 1980s, it was not until publication of the results of the Women's Health Initiative (WHI) study in 2002 and the Million Women Study in 2003 that women and doctors started reconsidering the use of HRT and sales of HRT started to drop. This paper evaluates the impact of the publication of these two landmark studies on the expected and observed changes in the incidence of breast cancer.Between 2001–2002 and 2005–2006, sharp and significant reductions in the incidence of breast cancer of up to 22% were reported in many US and European populations, temporally consistent with the drop in usage of HRT. Declines in the rates of breast cancer were strongest for 50–60-year-old women (those most likely to be current users of HRT), affected mainly ER+ and PR+ cancers (those most strongly associated with HRT use), and were largest among women with the highest pre-decline prevalence of HRT use and the sharpest decline in its use.A considerable amount of scientific evidence supports the hypothesis that the decline in the incidence of breast cancer is in large part attributable to the sudden drop in HRT use following publication of the WHI and Million Women studies. Nevertheless, the problem of how to advise women contemplating HRT use today remains. Medical relief will remain necessary for many women with menopausal complaints, and so new therapeutic options need to be explored.     

Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project

The authors studied obesity and fat distribution in relation to the occurrence of hot flashes in a population-based study comprising 2904 women aged 40–44 and 569 women aged 54–69 presenting for mammographic screening (the DOM-project). Women aged 40–44 in the upper tertiles of Quetelet's index and waist/hip ratio reported hot flashes significantly more often than women in the respective lower tertiles. These associations were independent of each other and independent of age. After adjustment for age, waist/hip ratio and menopausal status, the odds ratio comparing the upper tertile of Quetelet's index to the lower tertile was 1.70 (95% confidence interval, 1.30 – 2.21). After adjustment for age, Quetelet's index and menopausal status, the odds ratio comparing the upper tertile of waist/hip ratio to the lower tertile was 1.37 (95% CI, 1.05 – 1.78). In women aged 54–69 no significant associations between Quetelet's index and complaints of hot flashes were observed. Women in the upper tertile of waist/hip ratio reported hot flashes more often than women in the lower tertile, but this result was not significant (OR 1.38; 95% CI, 0.87 – 2.22).     

Lifestyle alterations for the amelioration of hot flashes

Hot flashes are a common complaint among women as they transition through menopause. This article reviews the evidence of lifestyle alterations for the amelioration of hot flashes including obesity, exercise, smoking, relaxation techniques, and acupuncture. Further randomized controlled trials regarding these lifestyle alterations are needed to determine their full potential benefits regarding hot flashes.     

Differential effects of progestogens, by type and regimen, on estrogen-metabolizing enzymes in human breast cancer cells

OBJECTIVES: To investigate the in vitro effects of five progestogens commonly used in hormone replacement therapy (HRT) on estrogen-metabolizing enzymes in human breast cancer cells. METHODS: The human hormone-dependent breast cancer cell lines T47D, MCF-7, and MCF-7aro were cultured with estradiol (E(2)) and progestogens. The mRNA levels of estrogen-metabolizing enzymes were determined by RT-PCR or Northern blot, and enzyme activities by radiolabeled substrates. Cell proliferation was measured by bromodeoxyuridine incorporation. In vitro models for continuous combined regimen (CCR) and sequential combined regimen (SCR) were established to mimic the in vivo conditions of HRT. RESULTS: Medroxyprogesterone acetate (MPA) plus E(2) (10(-8)M) stimulated the mRNA levels and activities of estrogen-activating enzymes aromatase (at 10(-8)M MPA), 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1) (at 10(-6)M), and sulfatase (at 10(-8) to 10(-6)M) compared to E(2) only. Progesterone also stimulated enzyme activity, but to a lower magnitude. Levonorgestrel, norethindrone, and dienogest showed no enzyme stimulation. The estrogen-inactivating enzymes 17beta-hydroxysteroid dehydrogenase type 2 and sulfotransferase were not affected by any of the progestogens tested. However, all the progestogens (at 10(-8) to 10(-6)M) inhibited E(2)-stimulated cell proliferation. While increased aromatase and 17betaHSD1 activities were observed in the CCR model, no significant enzyme stimulation was observed in the SCR model. CONCLUSIONS: The present study suggested that progestogens exert different actions on estrogen-metabolizing enzymes in breast cancer cells dependent on the specific progestogen and regimen used. Further studies are needed to elucidate whether MPA, a progestogen currently used in HRT, leads to a higher risk of breast cancer development than other progestogens.     

Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition

Background

We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety.

Methods

After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n = 19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7).

Results

Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for ≥1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14–18), and 6.5 (IQR 4–11.5), respectively, reflecting a significant decrease (p = .0006). The response and remission rates were 56.3% (all responders were also remitters, having ≥50% decrease in HAM-D scores and final scores ≤7). Anxiety improved with treatment (p = .012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p = .009 and p = .008, respectively). Daytime but not nighttime hot flashes improved significantly.

Conclusions

These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition.     

Determinants of hot flashes and night sweats

Primary Objective: The purpose of this study was to identify determinants of hot flashes and night sweats, two vasomotor symptoms associated with the hormonal changes of the menopause transition.

Methods: Participants were 293 women, aged 45 to 55, randomly selected from automated demographic and membership records of a health maintenance organization in the northeast USA. Letters were mailed to eligible women, followed by face-to-face interviews.

Results: Hot flashes during the month before interview were reported by 57% of the participants, although only 9% of the entire sample reported hot flashes to be “bothersome”. Night sweats were reported by 36% of all participants, with 6% reporting night sweats to be “bothersome”. Fifty-four percent of women reporting hot flashes also reported night sweats. In logistic regression analyses that controlled for menopause status and use of hormone therapy (HT), daily alcohol consumption significantly increased the risk of hot flashes, night sweats, and bothersome night sweats. Higher education and an excellent self-rating of health decreased the risk of night sweats, but not hot flashes. Smoking increased the risk of bothersome hot flashes, but not bothersome night sweats.

Conclusions: In logistic regression analyses, alcohol consumption was a significant predictor of vasomotor symptoms. A slightly different set of variables were associated with hot flashes compared to night sweats.

Résumé. Objectif premier: Cette étude a pour objet d’identifier les déterminants des bouffées de chaleur et des sudations nocturnes, deux symptômes vasomoteurs associés aux changements hormonaux de la transition ménopausique.

Méthodes: Les participants sont 293 femmes choisies au hasard à partir d’enregistrements automatiques de données démographiques des membres d’une organisation de surveillance de la santé du nord ouest des USA. Des lettres ont été adressées aux femmes retenues, suivies d’entretiens face à face.

Résultats: 57% des participantes on fait état de la survenue de bouffées de chaleur dans le mois qui a précédé l’entretien, mais seulement 9% ont mentionné en avoir été incommodées. 36% ont connu des sudations nocturnes, dont 6% ont été incommodées. 54% des femmes ayant fait état de bouffées de chaleur ont également connu des sudations nocturnes. Les analyses de régression logistique qui stabilisent l’effet du statut de la ménopause et du traitement hormonal (TH) indiquent que la consommation quotidienne d’alcool accroît les risques de bouffées de chaleur, de sueurs nocturnes et de sudation nocturne incommodante. Une plus grande éducation et un excellent auto contrôle de la santé diminuent les risques de sudations nocturnes, mais non de bouffées de chaleur.

Conclusion: Les analyses de régression logistique montrent que la consommation d’alcool est un excellent prédicateur des symptômes vasomoteurs. Les bouffées de chaleurs sont associées à un groupe de variables légèrement différent de celui des sueurs nocturnes.

Zusammenfassung. Studienziel: Sinn dieser Studie war es, Determinanten für Hitzwallungen und Nachtschweiß zu identifizieren, zwei vasomotorische Symptome, die mit den hormonellen Veränderungen des menopausalen Überganges einhergehen.

Methoden: Teilnehmerinnen waren 293 Frauen von 45 bis 55 Jahren, die nach Zufallskriterien aus elektronischen demographischen und Mitglieder-Verzeichnissen einer Gesundheitsorganisation im Nordosten der USA gezogen worden waren. Briefe wurden an auffindbare Frauen verschickt, gefolgt von persönlichen Interviews.

Ergebnisse: Hitzewallungen in den Monaten vor dem Interview wurden von 57% der Teilnehmerinnen angegeben, aber nur 9% der gesamten Stichprobe berichteten, dass ihnen die Hitzewallungen unangenehm seien. Nachtschweiß wurde von 36% aller Teilnehmerinnen angegeben, von denen 6% berichteten, dass ihnen das nächtliche Schwitzen unangenehm sei. 54% der Frauen, die über Hitzewallungen berichteten, gaben auch an, unter Nachtschweiß zu leiden. Unter Zugrundelegung desselben menopausalen Status und derselben begleitender Hormonbehandlung zeigte sich in logistischen Regressionsanalysen, dass täglicher Alkoholkonsum das Risiko von Hitzewallung, Nachtsschweiß und das Unwohlsein bei Nachtschweiß signifikant erhöhte. Höhere Bildung und eine besonders gute Selbsteinschätzung der eigenen Gesundheit senkten das Risiko von Nachtschweiß, nicht aber das von Hitzewallungen. Rauchen erhöhte das Risiko von Unwohlsein bei Hitzewallungen, nicht aber das Unwohlsein bei Nachtschweiß.

Zusammenfassung: In logistischen Regressionsanalysen erwies sich Alkoholkonsum als signifikantes Vorhersagekriterium für vasomotorische Symptome. Verglichen mit Nachtschweiß war ein leicht veränderter Satz von Variablen mit Hitzewallungen verknüpft.

Resumen. Objetivo principal: el propósito de este estudio fue identificar los determinantes de los sofocos y sudores nocturnos, dos síntomas vasomotores asociados con los cambios hormonales de la transición menopáusica.

Métodos: las participantes fueron 293 mujeres, de 45 a 55 años de edad, seleccionadas aleatoriamente a partir de registros automatizados demográficos y de afiliación a una organización para el mantenimiento de la salud, en el nordeste de EE.UU. Se enviaron cartas circulares a las mujeres potencialmente elegibles, que fueron seguidas de entrevistas personales.

Resultados: el 57% de las participantes dijeron haber tenido sofocos durante el mes anterior a la entrevista, aunque sólo el 9% de toda la muestra indicó que los sofocos habían sido “molestos”. Los sudores nocturnos fueron reportados por el 36% de las participantes, el 6% de las cuales señaló que los sudores nocturnos eran “molestos”. El cincuenta y cuatro por ciento de las mujeres que experimentaron sofocos también dijeron haber tenido sudores nocturnos. En los análisis de regresión logística que controlaban el status de menopausia y el uso de terapia hormonal (HT), se comprobó que el consumo diario de alcohol incrementaba el riesgo de padecer sofocos, sudores nocturnos y sudores nocturnos molestos. Un nivel educativo alto y una excelente valoración de la propia salud disminuían el riesgo de padecer sudores nocturnos, pero no de sofocos. El consumo de tabaco incrementaba el riesgo de sufrir sofocos molestos, pero no de sudores nocturnos molestos.

Conclusiones: en los análisis de regresión logística, el consumo de alcohol fue un predictor significativo de los síntomas vasomotores. El conjunto de variables asociadas con los sofocos era ligeramente diferente al de las variables asociadas con los sudores nocturnos.     

Update of the evolution of breast cancer incidence in relation to hormone replacement therapy use in Belgium

Background

Several studies reported a decrease in breast cancer (BC) incidence, subsequent to the decrease in hormone replacement therapy (HRT) use.

Aim

Although Belgium has one of the highest incidences of BC in Europe and one of the highest rates of HRT use, we were unable, in a previous study, to observe a significant association between BC incidence and HRT changes. In this updated report we added the BC data from incidence years 2007 and 2008.

Material and method

We used European standardized incidence rates for invasive BC in the age class 50–69 years for Flanders (1999–2008), Brussels and Wallonia (2004–2008), obtained from IMS Health HRT sales data (1997–2008) for Brussels, Flanders and Wallonia. The association between BC incidence and HRT use was analyzed using generalized estimating equations (GEE) in order to take into consideration the dependency between the subsequent data points.

Results

There was a significant association between the invasive BC incidence rate and estimated rate of HRT users in the previous year: p-value < 0.001.

Conclusion

Although this study is hampered by a number of limitations, these data support the idea that the drop in BC incidence can be partly attributed to the decrease in HRT use. Since HRT remains the most used medication for climacteric symptoms, we encourage the creation of a prospective registry in Europe, collecting detailed data in various European countries, in order to assess the adjusted increase in BC risk associated with HRT, which may be population and regimen dependent.     

Menopausal symptoms following breast cancer treatment: A qualitative investigation of cognitive and behavioural responses

Objectives

Menopausal symptoms – hot flushes and night sweats (HF/NS) – are particularly troublesome for women who have undergone breast cancer treatment. Non-medical treatments, such as cognitive behaviour therapy, are being developed but there is a lack of information about cognitive and behavioural reactions to HF/NS in breast cancer patients.

Methods

Thirty-five women who had completed active breast cancer treatment with at least 10 HF/NS per week completed questionnaires assessing HF/NS, mood and beliefs, and took part in interviews to elicit cognitive and behavioural reactions and a thematic content analysis used to analyse the data.

Results

The mean weekly frequency of HF/NS was 76 (SD = 46) (57 HF and 19 NS). Smokers reported significantly more night sweats, but BMI and mood were not associated with HF/NS frequency. Cognitive and behavioural responses were varied but broadly similar to those of well women. The main cognitive themes were: embarrassment/social anxiety, loss of control, beliefs about NS, sleep and tiredness, and the main behaviours were: carry on and ignore them, cool down, avoidance, communication with others.

Conclusions

The results are discussed within a cognitive behavioural framework and might inform the development of psychological interventions for these treatment related symptoms.     

Management of menopausal symptoms in breast cancer patients

In breast cancer patients, menopausal symptoms such as hot flashes, urogenital problems, musculoskeletal symptoms and cognitive dysfunction are common, regardless of age at diagnosis. They affect quality of life and systemic therapy will worsen this. Endocrine and/or chemotherapy may induce temporary or permanent ovarian failure and can exacerbate these symptoms. Hormone therapy (HT) has been studied in breast cancer survivors, but safety has been questioned. The HABITS trial investigating estrogen-based HT, as well as the LIBERATE trial investigating tibolone, found a reduction in disease-free survival for those treated. Alternative strategies are needed, as menopause symptoms may reduce compliance with breast cancer treatments. This article reviews recently published strategies to tackle menopausal problems in breast cancer patients. Antidepressants may help with hot flashes. Acupuncture and hypnosis can also be used but the evidence is conflicting. For urogenital problems vaginal moisturizers or topical estrogens can be employed. A musculoskeletal syndrome induced by aromatase inhibitors (AIs) is frequently encountered and currently there are no effective treatment strategies. Bisphosphonates reduce AI-induced bone resorption and can also increase disease-free and overall survival. Standard-dose endocrine and chemotherapy are associated with a decline in cognitive function.     

Why a consensus conference on hormone replacement therapy and the cardiovascular system?

A recent randomized, placebo-control study of a combination of conjugated estrogens (0.625 mg) and medroxyprogesterone acetate (2.5 mg) known to bring considerable advantages to post-menopausal women, has concluded that the risks associated with its use outweigh the benefits. On the strength of these data the manufacturer began recommending that physicians consider alternatives to their product to treat post-menopausal symptoms. Since women take hormone replacement therapy (HRT) for compelling health reasons, it is important, not only to evaluate the new evidence, but also to translate it into terms which can be understood by women and their physicians. Although the focus of this conference is on the cardiovascular system, in order to place the present controversy in its proper perspective, it is necessary to consider also other adverse effects that frighten women, first and foremost, a possible increased risk of breast cancer. For several years it has been reported that there is an increased risk of invasive breast cancer with increased duration of HRT use, similar to what has been found for oral contraceptives. The situation is however, entirely different when addressing HRT and risk of cardiovascular diseases (CVD). Here, a large body of evidence has, for years, pointed to a protective effect. Therefore, in the case of cardiovascular risk, we must proceed very cautiously and weigh the evidence, before concluding that HRT has indeed a negative effect on cardiovascular diseases. To properly do so, we must evaluate the validity and applicability of the findings presented in the latest study, since evidence indicates that the results of the study may not be applicable to women seeking HRT at the time of menopause. We also need to try and outline an overall “risk-benefit profile” for the use of HRT and we must aim at establishing a true dialogue between all parties concerned. Finally, we must obtain information, or state the lack of it, on possible different effects among the various estrogens, routes of administration and dosages, as well as possible different actions of the various progestins, their dosages and routes of administration.     

Interaction between menopausal status and obesity in affecting breast cancer risk

Obesity has a complex relationship to breast cancer risk that differs in premenopausal and postmenopausal women. Before the menopause, the level of adiposity is inversely related to risk, indicative of a protective effect, whereas in postmenopausal women, particularly the elderly, the association is a positive one, consistent with obesity being a risk factor. The importance of high estrogen production in adipose tissue, with consequent elevation of circulating biologically available estradiol, in the promotional effect of obesity on postmenopausal breast carcinogenesis is well established; the resulting tumors express both estrogen and progesterone receptors. The mechanism(s) for the protective effect in premenopausal women is less well understood, but the breast cancers that do develop in the presence of obesity are most often estrogen and progesterone receptor negative, consistent with the selection of non-estrogen-dependent tumor cells which are dependent on growth factors such as insulin, insulin-like growth factor-I and some adipokines. The influence of menopausal status on the relationships between adiposity and breast cancer appears to be modified within each category by age; the protective effect before the menopause may be limited to younger women (<35 years), and the adverse effect was found to apply specifically to older postmenopausal women. Although randomized trials of weight reduction for postmenopausal breast cancer prevention have not been performed, observational studies suggested that risk reduction does occur; in addition, other health benefits of weight control need to be considered regardless of menopausal status.     

Defining menopausal status in epidemiologic studies: A comparison of multiple approaches and their effects on breast cancer rates

Objectives

Menopausal status is a common covariate in epidemiologic studies. Still, there are no standard definitions for menopausal status using observational data. This study assesses distinctions between menopausal status definitions using commonly collected epidemiologic data, and explores their impact on study outcomes using breast cancer rates as an example.

Study design

Using survey data from 227,700 women aged 40–64 who received screening mammograms from the Breast Cancer Surveillance Consortium, we classified menopausal status under five different definitions: one complex definition combining multiple variables, two definitions using age as a proxy for menopausal status, one based only on menstrual period status, and one based on age and menstrual period status.

Main outcome measures

We compared the distribution of menopausal status and menopausal status-specific breast cancer incidence and detection rates across definitions for menopausal status.

Results

Overall, 36% and 29% of women were consistently classified as postmenopausal and premenopausal, respectively, across all definitions. Menopausal status-specific breast cancer incidence and detection rates were similar across definitions. Rates were unchanged when information regarding natural menopause, bilateral oophorectomy, hormone therapy, and timing of last menstrual period were sequentially added to definitions of postmenopausal status.

Conclusions

Distinctions in menopausal status definitions contribute to notable differences in how women are classified, but translate to only slight differences in menopausal status-specific breast cancer rates.     

Hormone replacement therapy (HRT), breast cancer and tumor pathology

Within an average observation period of 5–6 years, several clinical trials reported an increased risk of breast cancer due to hormone replacement therapy (HRT). However, it remains disputable, whether the increased rate of breast cancers detected within the given time frame is indeed due to newly induced tumors and thus constitutes HRT-initiated primary breast cancers. Onco-pathologically speaking it appears more likely that HRT stimulates the growth of already existing small tumor nests which – due to their small size – would otherwise go undiagnosed. The major arguments are:

1.

Cancer research has established that malignant tumors, including breast cancer, need an average of 5–10 years to expand from a single malignant cell to a lesion of 5–10 mm diameter. A time period of only 5 years, as covered by the respective studies, may well be too short to permit the detection of tumors primarily induced by HRT.