Systemic Menopausal Hormone Therapy Research Articles

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes

We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.

Associations between arterial health and sexual function in women aged 60-64 years.

Female sexual dysfunction is very common, but its determinants remain under-investigated. Vasculogenic impairments are suggested to be related to female sexual dysfunction, but previous literature regarding the association is scarce. This study aims to study the association between arterial health and female sexual function in women in their 60s. The sample for this cross-sectional study comprised 117 women (aged 60-64 years) who participated in the Finnish Retirement and Aging study. Arterial health was measured according to the participants' pulse wave velocity, ankle-brachial index, blood pressure, and pulse pressure. Sexual function was measured using the Female Sexual Function Index, which resulted in a total score and six sub-scores. Associations were examined using multivariable regression analyses, which were adjusted for age, relationship happiness, systemic menopausal hormone therapy and/or local estrogen, smoking, alcohol risk use, body mass index, and depressive symptoms. Higher diastolic blood pressure was associated with a higher total Female Sexual Function Index score (β = 0.24, 95% confidence interval [CI] 0.07-0.41) and with higher desire (β = 0.02, 95% CI 0.01-0.04), arousal (β = 0.04, 95% CI 0.01-0.08), lubrication (β = 0.04, 95% CI 0.002-0.08), satisfaction (β = 0.03, 95% CI 0.003-0.05), and pain (β = 0.06, 95% CI 0.02-0.10) sub-scores. Also, higher ankle-brachial index was associated with higher satisfaction sub-score (β = 2.10, 95% CI 0.44-3.73) and lower pulse pressure was associated with higher orgasm sub-score (β = 0.03, 95% CI 0.0002-0.06). Other associations between ankle-brachial index and Female Sexual Function Index scores were statistically insignificant, but considering the magnitude the findings may imply clinical significance. Systolic blood pressure and pulse wave velocity were not associated with sexual function. This study suggested a plausible association between higher diastolic blood pressure and female sexual function, but considering clinical significance our findings suggest an association between higher ankle-brachial index and good sexual function in women in their 60s.

A systematic review and critical appraisal of menopause guidelines

Objective and rationaleTo identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples.DesignSystematic review.Data sourcesOvid MEDLINE, EMBASE,...

Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study

BackgroundThere are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set.MethodsData were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995–1997) and HUNT3 (2006–2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40–69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20–69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders.ResultsIn the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14–1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16–1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16–1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06–1.30; compared with never users).ConclusionsLong-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.

Menopause and genitourinary health: optimal support and correction of disorders

The vulva, vagina, lower urinary tract, and pelvic floor have the same embryonic origin. Thus, all of the abovementioned organs are equally sensitive to estrogen deficiency and menopausal hormone therapy due to expression of the respective receptors. Genitourinary syndrome of menopause (GSM) is a concept first introduced in 2013 to provide a more complete definition of the consequences of estrogen deficiency in urogenital tissues and reflect the full range of vaginal and urinary symptoms that women experience during menopause. The term broadly reflects the condition, which, unlike the older term “vulvovaginal atrophy”, is not limited to a single symptom of dyspareunia and includes women who are not sexually active. The consequences of GSM significantly alter the quality of life of most menopausal women. Some patients with symptoms of vulvovaginal atrophy completely stop their sexual activity (58 %) and avoid sexual intimacy (55%). Various forms of urinary disorders also alter activities of daily living, sleep, sexual activity, and can lead to social isolation and loss of self-respect. Women with recurrent vulvovaginal infection often have to seek medical care. Estrogen therapy during menopause is pathogenetically justified. Estrogens administered intravaginally are more effective in relieving the symptoms of GSM, both objectively and subjectively, than their systemic use. Up to 40% of women receiving systemic menopausal hormone therapy do not have the expected effect of estrogens on the urogenital tract. If the symptoms of GSM prevail, it is advisable to consider monotherapy with local estrogens or combine it with systemic therapy instead of increasing a dose of the latter. The article presents a clinical case of a personalized approach to solving the issue of vulvovaginal atrophy combined with a mixed urinary incontinence (MUI) in a postmenopausal female patient.

Association between menopausal hormone therapy use and mortality risk: a Swedish population-based matched cohort study

Background The net effect of menopausal hormone therapy on the risk of death is understudied, and current evidence is conflicting. Our aim was to investigate the association between menopausal hormones and risk of all-cause, cardiovascular, and cancer-specific mortality, based on the Swedish Prescribed Drug Registry and National Patient Registry. Methods This Swedish population-based matched cohort study included all women, 40 years or older, who had received at least one prescription of systemic menopausal hormone therapy between 2005–2014 (n = 290,186), group level matched 1:3 to non-users (n = 870,165). Multivariable conditional logistic regression models estimated the relative risk of all-cause and cause-specific mortality, adjusting for several clinical factors and comorbidities. Results Ever-use of menopausal hormones was associated with a slightly lower overall odds of all-cause (OR = 0.97, 95%CI 0.95–0.98) and cardiovascular (OR = 0.97, 95%CI 0.95–0.99) mortality, whilst 30% lower overall odds of cancer-related mortality (OR = 0.70, 95%CI 0.68–0.72) was shown. The odds of all-cause and cancer-related mortality were consistently reduced among women who began menopausal hormone therapy ≤60 years, whereas the association with cardiovascular mortality was inconsistent. In contrast, oestrogen-only therapy was associated with elevated odds of all-cause (OR = 1.14, 95%CI 1.11–1.16) and cardiovascular mortality (OR = 1.04, 95%CI 1.01–1.06) among women who began treatment at ≥70 years. Among current users, oestrogen-only therapy was associated with higher odds of all-cause (OR = 1.48, 95%CI 1.44–1.52) and cardiovascular mortality (OR = 1.24, 95%CI 1.20–1.28), whereas past use of oestrogen-only therapy suggested lower odds of mortality. Conclusions Our generalisable data suggest that early menopausal hormone treatment initiation does not increase the odds of mortality. However, the role of oestrogens in particularly cardiovascular mortality remains to be investigated.

The menopause after cancer study (MACS) - A multimodal technology assisted intervention for the management of menopausal symptoms after cancer – Trial protocol of a phase II study

AimsThis study will aim to assess if a composite intervention which involves a specific evidence-based intervention for management of insomnia and non-hormonal pharmacotherapy to manage vasomotor symptoms (VMS) of menopause can improve quality of life for patients experiencing troublesome VMS after cancer who are not eligible for standard systemic menopausal hormone therapy (MHT). Participants will be asked to nominate a partner or companion to support them during this process as an additional form of support. BackgroundThe menopause transition and its symptoms represent a significant challenge for many patients after cancer treatment, particularly those for whom conventional MHT is contraindicated. These symptoms include hot flushes, night sweats, urogenital symptoms as well as mood and sleep disturbance. These symptoms can exacerbate the consequences of cancer and its treatment. MethodsWe will recruit 205 women who meet inclusion criteria and enrol them on a composite intervention which consists of four parts: (1) use of non-hormonal pharmacotherapy for the management of troublesome vasomotor symptoms of menopause tailored to the timing of predominant symptoms, (2) digital cognitive behavioural therapy for insomnia through the web based Sleepio service, (3) access to information regarding self-management strategies for the common symptoms of menopause and their consequences and (4) identification of a partner or other support person who commits to providing support during the study period. OutcomesThe primary outcome will be cancer specific quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). Secondary outcomes will include sleep quality, bother/interference of vasomotor symptoms and communication between couples about their cancer diagnosis and their menopause experience. Sleep will be measured using the Sleep Condition Indicator (SCI) tool, bother/interference of vasomotor symptoms will be measured by the Hot Flush Rating Scale (HFRS) and communication will be measured using the Couples’ Illness Communication Scale (CICS). These validated scales will be administered at baseline, four weeks, three months and six months. RegistrationThis study is registered on ClinicalTrials.gov with number NCT 04766229.

Prediagnostic use of estrogen-only therapy is associated with improved colorectal cancer survival in menopausal women: a Swedish population-based cohort study

Background Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. Methods This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. Results Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44–0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59–0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02–1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06–2.44) in older women, but no association was shown for all-cause mortality. Conclusions Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear.

Menopausal hormone therapies and risk of colorectal cancer: a Swedish matched-cohort study.

Menopausal hormone therapy (MHT) has been associated with various malignancies. To investigate the association of various MHT regimens with the risk of colorectal cancer (CRC). All MHT ever-users (n=290186) were included through the Swedish Prescribed Drug Registry, with a 1:3 group-level matching to non-users. Ever-users were defined as women who received ≥1 dispensed prescription of systemic MHT during 2005-2012 in Sweden. All CRC cases after drug initiation were extracted from the Swedish Cancer Registry. The association was assessed by multivariable conditional logistic and Cox regression models, presented as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) considering different regimens, duration and age at treatment initiation. Compared with non-users, MHT users had an overall reduced odds for colon (OR=0.67, 95% CI 0.63-0.72) and rectal adenocarcinoma (OR=0.66, 95% CI 0.60-0.73), especially among women aged 40-60years. Current users of oestrogen-only preparations (E-MHT) showed a reduced odds (colon OR=0.73, 95% CI 0.65-0.82; rectal OR=0.76, 95% CI 0.64-0.90) compared to non-users, particularly with oestradiol and oestriol. Past E-MHT use showed stronger odds reductions (colon OR=0.49, 95% CI 0.43-0.56; rectal OR=0.36, 95% CI 0.28-0.45). Current use of oestrogen combined progestin therapy (EP-MHT) indicated a less prominent odds reduction (colon adenocarcinoma OR 0.62, 95% CI 0.54-0.72; rectal adenocarcinoma OR=0.60, 95% CI 0.49-0.74) than past users. Tibolone showed an increased risk of left-sided colorectal adenocarcinoma. Oral and cutaneous MHT usage showed similar patterns. MHT use may decrease colorectal adenocarcinoma risk, for both E-MHT and EP-MHT, and especially in past users.

Prescribing of menopausal hormone therapy in Germany: Current status and changes between 2004 and 2016.

Prescribing of menopausal hormone therapy (MHT) declined drastically after publication of the Women's Health Initiative's (WHI) findings in 2002, but studies on longer-term trends and details of use are scarce. We used the German Pharmacoepidemiological Research Database (GePaRD) containing health insurance claims data from ~25 million persons. Using data from 2004-2016, we conducted cross-sectional analyses to determine the prevalence of MHT use overall and by type and route of administration in women aged 45-75. In longitudinal analyses, we assessed MHT use over 5 years and compared the patterns between different time periods. From 2004 to 2016, prevalence of systemic MHT prescriptions decreased by >60% in women aged 55-65 and by >50% in women aged 50 and 70 years old. Prevalence declined for most types and routes of administration at all ages (-16% to -79%) with some exceptions, for example, local MHT (vaginal estrogen). Among 50-year-old women in 2012, 6% were already prescribed systemic MHT at age 49 and of the remaining women, 16% were newly prescribed systemic MHT before age 55. At all ages, the cumulative dose of systemic MHT prescribed over 5 years was lower in the period 2012-2016 compared to 2005-2009 (-6% to -46%). For most types of MHT and all age groups, prevalence declined considerably between 2004 and 2016 in Germany. The cumulative dose per MHT user also decreased, suggesting a trend towards a shorter duration of use.

Current treatment options for genitourinary syndrome

At the onset of menopause, the urogenital symptoms begin to develop simultaneously with vasomotor symptoms: vaginal soreness, itching and dryness, dyspareunia, etc. The development of atrophic changes in the urogenital tract greatly reduces the quality of life and is a risk factor for the development of recurrent urinary tract infections. More than 60% of postmenopausal women, who do not take systemic menopausal hormone therapy (MHT), suffer from vaginal atrophy experience symptoms. The article discusses and evaluates effectiveness of various therapies for genitourinary syndrome of menopause (GSM). Nonhormonal lubricating gels are recommended as the first-line therapy. Local intravaginal administration of estrogens is used in moderate to severe vulvovaginal atrophy and in the absence of contraindications. Women with estrogen-dependent cancers can use low doses of local estrogen against the background of Tamoxifen therapy. New promising therapies for GSM are presented: ospemifene, an oral active selective estrogen receptor modulator (SERM), laser therapy, dehydroepiandrosterone. Even though the urogenital atrophy is a common disease, administration frequency of local estrogens as therapy is low. Basic principles for treatment of urogenital atrophy include alleviation of symptoms and restoration of normal blood supply to the vaginal epithelium and urothelium wall and mucous membrane. The therapy should be initiated early and the response time to therapy will depend on the degree of baseline atrophy. Vaginal moisturizers and lubricants can be used in combination with or separately from natural estrogens in cases when patients have medical contraindications to estrogen treatment.

Associations between menopausal hormone therapy and sleep disturbance in women during the menopausal transition and post-menopause: data from the Norwegian prescription database and the HUNT study

BackgroundImpaired sleep is common in menopausal women. The aim was to examine associations between uses of systemic menopausal hormone therapy (MHT) and sleep disturbance in a large population sample.MethodsFemale participants aged 45 to 75 years were selected from the Norwegian Health Study in Nord-Trøndelag (HUNT3, 2006–2008) (N = 13,060). Data were linked to the Norwegian Prescription Database, identifying use of prescribed MHT and use of sleep medication. Data were analyzed using multiple linear regression.ResultsIn total, 996 women used systemic MHT (7.6%), with the highest prevalence of 10.3% among women 55 to 64 years of age. Despite high reports of frequent nocturnal awakening (24.7%) and high reports of hot flashes, use of MHT was low in this large population based survey. Although MHT use was associated with more sleep disturbance in unadjusted analyses, the association was not significant after adjusting for relevant covariates. Using sleep medication, reporting poor health, tobacco and alcohol use, doing daily exercise, having higher levels of anxiety, and being less satisfied with life were factors showing the strongest associations with sleep disturbance.ConclusionThe lack of association between MHT and sleep disturbance suggests that other factors, such as self-perceived good health, a healthy lifestyle and anxiety/depression, are more relevant to sleep than MHT.

Menopausal hormone therapy treatment options and ovarian cancer risk: A Swedish prospective population-based matched-cohort study.

Although menopausal hormone therapy (MHT) seemingly increases the risk of ovarian cancer, evidence is insufficient whether the risk varies between various MHT formulations, regimens and administration modes. With the aim of filling these knowledge gaps, we investigated the effect of different MHT treatment options on the risk of ovarian cancer. This prospective Swedish population-based matched-cohort study included all women ≥40 years having used systemic MHT between 2005 and 2012 (288,950 ever-users), group-level matched (1:3) to 866,546 nonusers. MHT use was ascertained from the Swedish Prescribed Drug Registry and data was linked to several national health data registries. Multivariable conditional logistic regression provided odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for parity, and comorbidities. Current EP-MHT use was associated with a modestly increased risk of ovarian cancer (OR = 1.38, 95% CI 1.18-1.62), while no consistent risk was found among past users (OR = 1.00, 95% CI 0.84-1.18). Current continuous testosterone derived (OR = 1.50, 95% CI 1.15-1.96) regimens increased the risk whereas progesterone derived (OR = 1.48, 95% CI 1.00-2.21) regimens increased the risk marginally. Nonsignificant positive associations were observed for sequential regimens (OR = 1.87, 95% CI 0.70-5.08; OR = 1.54, 95% CI 0.96-2.47, respectively). An inverse relationship was observed for all E-MHT use (OR = 0.25, 95% CI 0.22-0.29), but this association might partly be explained by underreporting of oophorectomies or tubal ligations. Current cutaneous EP-MHT (OR = 1.28, 95% CI 0.81-2.02) suggested a possibly lower risk than oral MHT (OR = 1.48, 95% CI 1.25-1.75). In conclusion EP-MHT, notably continuous regimens, were associated with a modestly increased risk of ovarian cancer. The role of E-MHT requires further clarification.

Role and Place of Menopausal Hormone Therapy in Treatment of Symptoms of Lower Urinary Tracts in Women of 40+ Age

The objective: to evaluate the results of a comparative analysis of the clinical efficacy of various compositions, combination and pharmacological effects of drugs (antispasmodic, hormones, of plant origin) for symptoms of the lower urinary tract in women in the premenopausal period.Materials and methods. The efficacy of the treatment of 120 premenopausal women with symptoms of the lower urinary tract was studied. The complaints, uroflow metrics, sociological survey of results to identify the symptoms of menopausal syndrome by the MRS scale, as well as the level of anxiety by the S. Spielberg scale were evaluated as criteria for its assessment in the dynamics before and after 3, 6, 12 months. The data were statistically processed using Student’s and Fisher’s criteria.Results. There have been revealed the frequency and nature of complaints in women aged 40 plus, manifested in the form of urinary disorders, gynecological symptoms of menopausal syndrome. The results of treatment with the use of monotherapy with mirabegron, as well as in combination with menopausal hormone therapy (MHT) and herbal medicine, have been studied. There has been proven clinical advantage in treating women with genitourethral syndrome, using a combination of systemic MHT and symptomatic.Conclusions. Treatment of lower urinary tract symptoms in women of perimenopausal age with the presence of menopausal manifestations requires an integrated approach with the inclusion of systemic menopausal hormone therapy, among which objectively proven advantage of the drug, which includes levonorgestrel, as well as symptomatic therapy.

Differential Effects of Progestogens Used for Menopausal Hormone Therapy.

Recommendations regarding menopausal hormone therapy continue to evolve as more studies are completed. Progestogens, indicated for endometrial protection in women on estrogen therapy who have an intact uterus, seem to confer greater health risks than estrogen alone. Thus, it is important for clinicians to be well informed when prescribing these medications. This review focuses on the different types and use of progestogens in women with an intact uterus using systemic menopausal hormone therapy.

Opportunities for prevention and correction of genitourinary menopausal syndrome

In the manifestation and development of urogenital atrophic processes associated with the onset of menopause, the leading role is played by the growing deficiency of estrogens. An important circumstance is the fact that genitourinar menopausal disorders are often accompanied by other climacteric disorders. In this regard, a key place in the prevention and correction of hypoestrogenic conditions is systemic menopausal hormone therapy. Among the representatives of systemic menopausal hormone therapy, clinical efficacy and low risk of possible complications were demonstrated by preparations containing 17b-estradiol in combination with drospirenone. In the literature there is a significant number of publications reflecting the positive effect of these drugs on the condition of women with vasomotor, psychoemotional climacteric disorders, with a decrease in bone mass. Also, these drugs are used in the therapy and prevention of atrophic processes of the urogenital tract. This allows us to apply this combination of hormones in the complex correction of systemic and local genitourinary menopausal disorders.

Managing menopausal symptoms after cancer: an evidence-based approach for primary care.

Impaired ovarian function and menopausal symptoms are common after cancer treatment. Menopausal symptoms often occur at an earlier age in women with cancer, and may be more severe than in natural menopause; they may be the most persistent and troubling sequelae of cancer. A third of female patients with cancer report dissatisfaction with the quality and length of physician-patient discussions about reproductive health, including menopause. Systemic menopausal hormone therapy is the most effective treatment for menopausal symptoms, but it is not suitable for all patients after cancer - where it is unsuitable, alternative effective non-hormonal treatments are available. Effective pharmacological agents available to treat vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, clonidine and gabapentin. There is increasing evidence supporting cognitive behavioural therapy for the treatment of vasomotor symptoms, in self-help or group settings. Vaginal atrophy can be treated with vaginal (topical) oestrogen with minimal systemic absorption; topical vaginal lubricants may help with vaginal dryness and dyspareunia, with some evidence suggesting that silicone-based products may be more effective than water-based ones. Bone health may be impaired in post-menopausal women with cancer or in cancer survivors, particularly in women with treatment-related menopause or in women receiving anti-oestrogen therapies; this should be managed in addition to menopausal symptoms. Primary care physicians should be aware of the troublesome and ongoing nature of menopausal symptoms after cancer, should discuss them with all patients after cancer treatment, and should consider treatment or referral to a specialist for appropriate management.

Menopausal hormone therapy and pancreatic cancer risk in women: a population-based matched cohort study.

The role of menopausal hormone therapy (MHT) in the development of pancreatic cancer is inconclusive owing to small studies and lack of proper study design. This population-based matched cohort study included all Swedish women who used systemic MHT between 1 July 2005 and 31 December 2012. For each user of MHT, three never-users of MHT were randomly selected, matched for childbirth, history of thromboembolic events, and previous hysterectomy, as well as for year of birth, diabetes, obesity, and smoking- or alcohol-related disorders. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MHT use and pancreatic cancer. The effect of MHT duration on pancreatic cancer development was calculated using multivariable Poisson regression. There were 290,186 ever-users of MHT and 870,165 matched never-users. During the follow-up, 311 (0.0011%) ever-users of MHT and 1220 (0.0014) never-users developed pancreatic cancer. In a multivariable adjusted model, ever-users had a 23% reduced risk (OR 0.77; 95% CI: 0.68-0.87) of pancreatic cancer. This risk decreased by 35% (incidence rate ratio (IRR) 0.65; 95% CI: 0.33-1.27) in women who used MHT 1-2 years and by 60% (IRR 0.40; 95% CI: 0.18-0.88) in women who used MHT ≥ 3 years compared to women with <1 year of MHT use. The type of MHT did not change the results. Systemic MHT use might reduce the risk of pancreatic cancer.

Menopausal hormone therapy and cancer risk: An overestimated risk?

AimWe aimed to assess the overall cancer risk among contemporary menopausal hormone therapy (MHT) users in Sweden and the risk for different cancer types. MethodsA nationwide Swedish population-based cohort study including all 290,186 women aged ≥ 40 years having used systemic MHT during the study period (July 2005 and December 2012), compared with the Swedish female background population. MHT ever-use (all MHT, oestrogen-only MHT [E-MHT] and oestrogen plus progestin MHT [EP-MHT]) was based on the nationwide Prescribed Drug Registry. Cancer diagnoses were grouped into 16 different anatomical locations, for which standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. ResultsThe SIR of any cancer was 1.09 (95% CI: 1.07–1.11) following ever MHT, 1.04 (95% CI: 1.01–1.06) for E-MHT and 1.14 (95% CI: 1.12–1.17) for EP-MHT. The highest SIR was found for EP-MHT among users aged ≥70 years (SIR = 1.33, 95% CI: 1.26–1.40). The risk for invasive breast, endometrial or ovarian cancer combined was increased for any MHT (SIR = 1.31, 95% CI: 1.28–1.34). The risk of invasive breast cancer was increased following MHT and increased with age for EP-MHT users. The risk of gastrointestinal cancers combined was decreased (SIR = 0.90, 95% CI: 0.86–0.94), particularly the oesophagus (SIR = 0.81, 95% CI: 0.64–1.00), liver (SIR = 0.81, 95% CI: 0.65–0.99) and colon (SIR = 0.90, 95% CI: 0.84–0.95). ConclusionsMHT, notably EP-MHT, was associated with a limited increase in overall cancer risk. The increased risk of female reproductive organ cancers was almost balanced by a decreased risk of gastrointestinal cancers.

Menopausal hormone therapy and the risk of esophageal and gastric cancer.

A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR = 0.62, 95% CI 0.45-0.85, n = 46), gastric adenocarcinoma (OR = 0.61, 95% CI 0.50-0.74, n = 123) and esophageal squamous cell carcinoma (OR = 0.57, 95% CI 0.39-0.83, n = 33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR = 0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.