November 2022

Lopez-Pentecost M, Crane TE, Garcia DO, Kohler LN, Wertheim BC, Hebert JR, Steck SE, Shivappa N, Santiago-Torres M, Neuhouser ML, Hatsu IE, Snetselaar L, Datta M, Kroenke CH, Sarto GE, Thomson CA. Role of dietary patterns and acculturation in cancer risk and mortality among postmenopausal Hispanic women: results from the Women’s Health Initiative (WHI). Z Gesundh Wiss. 2022;30(4):811-822.

Objective
To investigate the association between dietary patterns and total and obesity-related cancers risk. Additionally, to examine if acculturation modifies this relationship.

Design

• Dietary intake of postmenopausal Hispanic women (N=5,482) enrolled in the Women’s Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores; Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted-Dietary Inflammatory Index (E-DII™).
• Associations were evaluated using Cox proportional hazards regression models.

Main findings

• 631 cancers and 396 obesity-related cancers were diagnosed over a mean-follow up of 12 years.
• Across dietary scores, there were no significant associations with cancer risk or mortality.
• Trend analysis suggest a potentially lower risk for total cancer related to the highest MexD score (HR 0.68, 95% CI 0.45-1.04, P-trend=0.03), and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37-1.16, P-trend=0.02), and aMED (HR 0.87, 95% CI 0.45-1.67, P-trend=0.04).
• Further analysis suggests less acculturated women with higher MexD scores had 56% lower risk for any cancer (HR 0.44, 95% CI 0.22-0.88, P-trend=0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04-0.76, P-trend=0.01) compared to more acculturated Hispanic women.

Take-home messages

• Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women.
• Less-acculturated, Spanish-preferred speakers, who reported consuming a more traditional Mexican diet may experience a lower risk for cancer and cancer mortality.

https://pubmed.ncbi.nlm.nih.gov/35602929/

Dixit A, Carden N, Stephens E, Chadwick M, Tamblyn J, Robinson L. Hormone replacement therapy subcutaneous implants for refractory menopause symptoms; the patient’s perspective. Post Reprod Health. 2022;28(2):79-91.

Background
For women with menopause symptoms refractory to standard hormone replacement therapy (HRT) preparations, HRT implants offer an alternative.

Objective
To evaluate women’s perceptions regarding efficacy, tolerability, satisfaction and safety of implant therapy.

Design

• A single centre service evaluation study performed at Birmingham Women’s & Children’s Foundation Hospital Trust.
• An anonymised semi-structured survey link was posted to all women (n = 397) recorded to have received HRT implant(s) at a tertiary Menopause clinic (May 1982 and Dec 2018).
• Women attending clinic (June 2020 to Sept 2020) were opportunistically invited to complete a written version of the survey.
• Data collected included demographics, medical and surgical history, therapy duration, type, indication and complications.
• Climacteric symptoms were assessed using the Greene Climacteric Scale.

Main findings

• Data was obtained for 119 women.
• The written survey yielded higher response rates (n = 73, 61.3%).
• Most respondents were 51-60 years old (n = 51 42.9%) and 87.4% (n = 104) were ‘White British’. 70 women used estradiol only implants. 30.1%% (n = 34) of patients reported a low Greene Climacteric Scale score (0-5).
• Subgroup analysis showed prevalence of sexual dysfunction and vasomotor symptoms across ages.
• There was a lower prevalence of psychological symptoms amongst ≥51 year olds.
• High satisfaction rates were reported.

Take-home messages

• Data from a large cohort is presented.
• Good symptom control, satisfaction and long-term efficacy was demonstrated.
• This study supports the value of HRT implants for refractory menopause symptoms.
• A national database of implant users would be a useful tool to record satisfaction scores and adverse events.

https://pubmed.ncbi.nlm.nih.gov/35599571/

Koçoğlu F, Kocaöz S, Kara P, Aşcı Ö. Relationship between menopausal symptoms and sleep quality in women during the climacteric period: a cross-sectional study. J Obstet Gynaecol. 2022;42(6):2393-2398.

Background
Sleep disorders are a common health problem in women in the climacteric period.

Objective             
To evaluate the relationship between the menopausal symptoms and sleep quality in women in the climacteric period.

Design

• This cross-sectional study was conducted on 383 women aged 40-64 years at the Cancer Early Diagnosis Screening and Training Centre.
• The data were collected with the questionnaire form, Menopause Rating Scale (MRS) and the Pittsburgh Sleep Quality Index (PSQI).

Main findings

• The most common menopausal symptoms were joint and muscle problems, physical and emotional fatigue, nervousness, hot flushes, unhappiness, anxiety, and sleep problems in order of frequency.
• The sleep quality was poor in 77.8% of the women in the study.
• A significant relationship was found between PSQI scores and the somatic and psychological subscale scores of the MRS in the presence of other variables that could affect sleep according to multiple linear regression analysis (p < .05).
• In addition, there was a weak positive significant relationship between the total PSQI score and the psychological and urogenital subscale scores of the MRS, in addition to a moderate positive significant relationship between the total PSQI scores and the total and somatic subscale scores of the MRS

Take-home message
Authors recommend training and consulting services provided by health care professionals and further experimental studies on the subject to decrease the negative effects of the somatic and psychological symptoms found to worsen sleep quality in women in the climacteric period.

https://pubmed.ncbi.nlm.nih.gov/35648883/

LeBlanc ES, Hovey KM, Cauley JA, Stefanick M, Peragallo R, Naughton MJ, Andrews CA, Crandall CJ. Cumulative Endogenous Estrogen Exposure Is Associated with Postmenopausal Fracture Risk: The Women’s Health Initiative Study. J Bone Miner Res. 2022;37(7):1260-1269.

Objective
To evaluate the relationship between cumulative endogenous estrogen exposure and fracture risk in 150,682 postmenopausal women (aged 50 to 79 years at baseline) who participated in the Women’s Health Initiative.

Design

• The authors hypothesized that characteristics indicating lower cumulative endogenous estrogen exposure would be associated with increased fracture risk and they determined ages at menarche and menopause as well as history of irregular menses from baseline questionnaires and calculated years of endogenous estrogen exposure from ages at menarche and menopause.
• Hence, incident clinical fractures were self-reported over an average 16.7 years of follow-up and multivariable proportional hazards models were used to assess the associations between the estrogen-related variables and incidence of any clinical fracture.

Main findings

• In fully adjusted models, those with the fewest years of endogenous estrogen exposure (<30) had an 11% higher risk of developing central body fractures and a 9% higher risk of lower extremity fractures than women with 36 to 40 years of endogenous estrogen exposure (the reference category).
• In contrast, women with the most years of endogenous estrogen exposure (more than 45 years) had a 9% lower risk of lower extremity fractures than the reference category.
• Women with irregular (not monthly) menstrual cycles were 7% to 8% more likely to experience lower extremity fractures than women with regular monthly cycles.

Take-home message
The findings of the study support the hypothesis that characteristics signifying lower cumulative endogenous estrogen exposure are associated with higher fracture risk.

https://pubmed.ncbi.nlm.nih.gov/35644990/

Mittal M, McEniery C, Supramaniam PR, Cardozo L, Savvas M, Panay N, Hamoda H. Impact of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol on cardiovascular markers in women diagnosed with premature ovarian insufficiency or an early menopause: a randomised pilot trial. Maturitas. 2022;161:18-26.

Background
The European Society for Cardiology has identified carotid femoral pulse wave velocity (cfPWV) as the gold standard cardiogenic biomarker for risk stratification of arterial disease. Menopause has been shown to augment the age-dependent increase in arterial stiffness, with hormone replacement therapy (HRT) being the mainstay of management of women diagnosed with EMPOI.

Objective
To compare the difference between micronised progesterone (MP) and medroxyprogesterone acetate (MPA) in combination with transdermal oestradiol (t-E2) on cardiovascular disease (CVD) risk markers in women diagnosed with an early menopause and premature ovarian insufficiency (EMPOI).

Design

• A pilot randomised prospective open-label trial.
• Women were randomised to either cyclical MP (Utrogestan® 200 mg) or MPA (Provera® 10 mg) in conjunction with t-E2 (Evorel® Patches 50mcg/day) for 12 months.
• Seventy-one subjects were screened, and baseline data are available for 57 subjects.
• Main outcome measure: Carotid-femoral pulse wave velocity (cfPWV).

Main findings

• PWV did not significantly change from baseline in either treatment arm.
• MP + t-E2 demonstrated a positive effect on traditional CVD markers, with a significant improvement seen in cardiac output (CO) (0.71±1.01mL/min, 95% CI 0.20 to 1.21) and reduction in diastolic blood pressure (DBP) (-3.43±6.31mmHg, 95% Cl -6.57 to -0.29) and total peripheral resistance (TPR) (-0.15±0.19mmHg⋅min⋅mL-1, 95% CI -0.24 to -0.05) after 12 months.
• MPA + t-E2, in contrast, did not demonstrate significant changes from baseline in traditional haemodynamic parameters.

Take-home message
The positive changes in traditional markers were not reflected in the cardiogenic biomarker, cfPWV, which has demonstrated a higher positive predictive value for cardiovascular events than traditional measurements.

https://pubmed.ncbi.nlm.nih.gov/35688490/

Hirsch H, Manson JE. Menopausal symptom management in women with cardiovascular disease or vascular risk factors. Maturitas. 2022;161:1-6.

Background

• Women with pre-existing cardiovascular disease (CVD) or vascular risk factors commonly experience bothersome symptoms of menopause, including vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM).
• Due to confusion surrounding the safety of menopausal hormone therapy (HT) in symptomatic women with CVD, evidence-based guidelines should be followed regarding identifying candidates for treatment and HT decision making.

Objective and design

• The aim of this review was to summarize best practices in the evaluation and treatment of VMS and GSM in women with pre-existing CVD, based on international expert consensus guidelines and/or expert opinion when data are scarce.
• For women with pre-existing CVD or vascular risk factors who are candidates for HT, guidelines often address the appropriate formulation, dose, and route of delivery.
• For women who are not candidates for HT, non-hormonal options were reviewed, and their safety and efficacy in treating VMS and GSM discussed.
• Due to increased knowledge of the role that pregnancy-related complications play in maternal risk for future CVD, these conditions were considered when addressing the use of systemic HT.
• Women at increased risk for future CVD without the use of HT, such as women with premature or early menopause, were also discussed, as well as the safely profile of HT in these special populations.

Take-home message
With worldwide rates of CVD increasing among women in midlife, it is important for clinicians to have clear guidelines for identifying candidates for hormonal and nonhormonal treatments for symptom management to safeguard the health and quality of life of these patients through the menopause transition and post-menopause.

https://pubmed.ncbi.nlm.nih.gov/35688488/

Xiao PL, Cui AY, Hsu CJ, Peng R, Jiang N, Xu XH, Ma YG, Liu D, Lu HD. Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis. Osteoporos Int. 2022;33(10):2137-2153.

Background
Osteoporosis is a common metabolic bone disorder in the elderly, usually resulting in bone pain and an increased risk of fragility fracture, but few summarized studies have guided global strategies for the disease.

Objective
To estimate the global, regional prevalence, and risk factors of osteoporosis.

Design

• This was a systematic review and meta-analysis.
• Authors conducted a comprehensive literature search through PubMed, EMBASE, Web of Science, and Scopus, to identify population-based studies that reported the prevalence of osteoporosis based on the World Health Organization (WHO) criteria.
• Authors pooled the epidemiologic data to estimate the global, regional prevalence, and potential risk factors of osteoporosis; then meta-regression and subgroup analyses were used to explore the sources of heterogeneity.
• The study was registered in the PROSPERO database (CRD42021285555).

Main findings

• Of the 57,933 citations evaluated, 108 individual studies containing 343,704 subjects were included.
• The global prevalence of osteoporosis and osteopenia was 19.7% (95%CI, 18.0%-21.4%) and 40.4% (95%CI, 36.9%-43.8%).
• Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from Oceania 8.0% to 26.9% in Africa).
• The prevalence was higher in developing countries (22.1%, 95%CI, 20.1%-24.1%) than in developed countries (14.5%, 95%CI, 11.5%-17.7%).

Take-home messages

• The present study indicates a considerable prevalence of osteoporosis among the general population based on WHO criteria, and the prevalence varies substantially between countries and regions.
• Future studies with robust evidence are required to explore risk factors to provide effective preventive strategies for the disease.

https://pubmed.ncbi.nlm.nih.gov/35687123/

Dias RC, Costa EH, Chrisostomo KR, Junior JK, Paiva ES, Azevedo PM, Skare TL, Nisihara RM. Fibromyalgia and menopause: an open study on postmenopausal hormone therapy. Minerva Obstet Gynecol. 2022 Jun 8. doi: 10.23736/S2724-606X.22.05085-0.

Background
Fibromyalgia women (FM) seems to get worse at menopause suggesting some influence of estrogens on its pathophysiology.

Objective
To study the influence of postmenopausal hormone therapy (HT) in FM, the relationship with sleep and FM impact.

Design

• The authors analyzed prospectively 69 menopausal women, divided in two groups, FM group (FMG; n=32) and comparison group (CG; n=28) submitted to HT for twelve weeks (1,2mg/g transdermal estradiol, 100 mg micronized natural progesterone oral/daily).
• Data on UQOL (Utian Quality of Life Questionnaire) and PSQI (Pittsburgh Sleep Quality Index) were obtained in both groups, at entrance and twelve weeks after HT. FM patients also completed the FIQ-R (Fibromyalgia Impact Questionnaire – revised) and FS (Fibromyalgia Severity).

Main findings

• FM patients improved significantly the FIQ-R (p=0.0001, median FIQ-R score 30% lower), mainly the severity of FM, assessed by FS (p<0.0001).
• Both groups had improved quality of life and sleep (UQOL: p=0.0001; p=0.001 – PSQI: p<0.0001; p=0.007, respectively).
• Differences between first and second PSQI were greater for CG than for FMG (p=0.008).

Take-home messages

• HT improved sleep and quality of life in both groups yet it was a significant clinical improvement seen by the FIQ and the FS tools in FM patients.
• These changes characterize improvement of functional status and symptoms severity.

https://pubmed.ncbi.nlm.nih.gov/35686636/

Heravi AS, Michos ED, Zhao D, Ambale-Venkatesh B, Doria De Vasconcellos H, Lloyd-Jones D, Schreiner PJ, Reis JP, Wu C, Lewis CE, Shikany JM, Sidney S, Guallar E, Ndumele CE, Ouyang P, Hoogeveen RC, Lima JAC, Vaidya D, Post WS. Oxidative Stress and Menopausal Status: The Coronary Artery Risk Development in Young Adults Cohort Study. J Womens Health (Larchmt). 2022;31(7):1057-1065.

Background
Low endogenous estrogen concentrations after menopause may contribute to higher oxidative stress and greater cardiovascular disease (CVD) risk; however, differences in oxidative stress between similarly aged premenopausal and postmenopausal women are not well-characterized on a population level.

Objective
To compare measures of oxidative stress according to menopausal status. The authors hypothesized that urinary isoprostane concentrations, a standard measure of systemic oxidative stress, are higher in women who have undergone menopause compared to premenopausal women.

Design
Investigators examined differences in urinary 8-isoprostane (iPF2α-III) and 2,3-dinor-8-isoprostane (iPF2α-III-M) indexed to urinary creatinine between 279 postmenopausal and 196 premenopausal women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, using linear regression with progressive adjustment for sociodemographic factors and traditional CVD risk factors.

Main findings

• Unadjusted iPF2α-III-M concentrations were higher among postmenopausal compared to premenopausal women (Median [25th, 75th percentile]: 1762 [1178, 2974] vs. 1535 [1067, 2462] ng/g creatinine; p = 0.01). Menopause was associated with 25.5% higher iPF2α-III-M (95% confidence interval [6.5-47.9]) adjusted for age, race, college education, and field center.
• Further adjustments for tobacco use (21.2% [2.9-42.6]) and then CVD risk factors (18.8% [0.1-39.6]) led to additional partial attenuation.
• Menopause was associated with higher iPF2α-III in Black but not White women.

Take-home message
Postmenopausal women had higher oxidative stress, which may contribute to greater CVD risk.

https://pubmed.ncbi.nlm.nih.gov/35675673/

Abenhaim HA, Suissa S, Azoulay L, Spence AR, Czuzoj-Shulman N, Tulandi T. Menopausal Hormone Therapy Formulation and Breast Cancer Risk. Obstet Gynecol. 2022;139(6):1103-1110.

Objective
To evaluate whether the increased risk of breast cancer is dependent on the formulation of menopausal hormone therapy (HT) used.

Design

• The authors performed a population-based case-control study of women aged 50 years or older using data from the U.K. Clinical Practice Research Datalink.
• Women with incident cases of breast cancer were age-matched (1:10) with a control group of women with comparable follow-up time with no history of breast cancer.
• Exposures were classified as ever or never for the following menopausal HT formulations: bioidentical estrogens, animal-derived estrogens, micronized progesterone, and synthetic progestin.
• Logistic regression analyses were performed to estimate the adjusted effect of menopausal HT formulation on breast cancer risk.

Main findings

• Between 1995 and 2014, 43,183 cases of breast cancer were identified and matched to 431,830 women in a control group.
• In adjusted analyses, compared with women who never used menopausal HT, its use was associated with an increased risk of breast cancer (odds ratio [OR] 1.12, 95% CI 1.09-1.15).
• Compared with never users, estrogens were not associated with breast cancer (bioidentical estrogens: OR 1.04, 95% CI 1.00-1.09; animal-derived estrogens: OR 1.01, 95% CI 0.96-1.06; both: OR 0.96, 95% CI 0.89-1.03).
• Progestogens appeared to be differentially associated with breast cancer (micronized progesterone: OR 0.99, 95% CI 0.55-1.79; synthetic progestin: OR 1.28, 95% CI 1.22-1.35; both OR 1.31, 0.30-5.73).

Take-home messages

• Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins.
• When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.

https://pubmed.ncbi.nlm.nih.gov/35675607/