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. Author manuscript; available in PMC: 2023 Mar 1.
Published in final edited form as: Atherosclerosis. 2022 Jan 22;344:13–19. doi: 10.1016/j.atherosclerosis.2022.01.016

Menopausal hormone therapy and risk of cardiovascular events in women with prediabetes or type 2 diabetes: A pooled analysis of 2917 postmenopausal women

Yilin Yoshida 1,5,6, Zhipeng Chen 2, Robin L Baudier 4, Marie Krousel-Wood 3,4,5, Amanda H Anderson 4, Vivian A Fonseca 1,6, Franck Mauvais-Jarvis 1,5,6
PMCID: PMC8905583  NIHMSID: NIHMS1778204  PMID: 35114556

Abstract

Background and aims:

The effect of MHT on cardiovascular disease (CVD) risk among women with prediabetes or type 2 diabetes (PreDM or T2DM) is unclear. We examined the association between ever or early use MHT and CVD risk in postmenopausal women with PreDM or T2DM, and the potential modifying effect of race.

Methods:

2,917 postmenopausal women with PreDM or T2DM were pooled from 3 prospective CVD cohorts (the Atherosclerosis Risk in Communities, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study). Ever (yes vs no) or early use of MHT (MHT initiated ≤ 5 vs > 5 years since menopause), and their associations with ischemic stroke, coronary heart disease (CHD), and atherosclerotic cardiovascular disease (ASCVD) were assessed using Cox proportional hazards models.

Results:

During a median follow-up of 15 years, 264 stroke, 484 CHD, and 659 ASCVD events were observed. In fully adjusted models, ever use of MHT was associated with reduced risk of stroke (hazard ratio 0.86, 95% CI 0.76–0.98), CHD (0.85, 0.74–0.98), and ASCVD (0.83, 0.73–0.95) in white women with PreDM or T2DM. Early use of MHT was associated with reduced risk of stroke (0.82, 0.72–0.95), CHD (0.85, 0.74–0.98), and ASCVD (0.82, 0.70–0.96) in the white group. No risk reduction with ever or early use of MHT was found for black women with PreDM or T2DM.

Conclusions:

MHT is associated with statistically reduced CVD risk among white but not black women with PreDM or DM. Race is an effect modifier in the association between MHT use and CVD.

Graphical Abstract

graphic file with name nihms-1778204-f0004.jpg

1. Introduction

The impact of menopausal hormone therapy (MHT) on cardiovascular disease (CVD) risk has been inconsistent across studies. While earlier studies reported a concerning trend toward harm 1, recent evidence is consistent with a neutral or favorable effect of MHT on cardiovascular health in healthy younger postmenopausal women (age <60 years) or those close in time (<10 years) to menopause onset 2,3. Findings from previous randomized controlled trials support the “timing” or “critical window” hypothesis4–6.

The effect of MHT on CVD outcomes in women with type 2 diabetes (T2DM) is mostly lacking due to no or limited inclusion of participants with T2DM in clinical trials 1,7,8. T2DM is one of the most common chronic conditions among postmenopausal women, a population that is also likely to be affected by moderate to severe vasomotor symptoms and in need of menopausal symptom management 9. However, T2DM has been considered a CVD equivalent, which is not recommended by the current guidelines for MHT 36.

Emerging evidence shows beneficial effects of MHT on glycemic control 10,11. MHT reduced insulin resistance, as represented by HOMA-IR by an average of 36%, a greater reduction than that in women without T2DM 12. Beyond improving glucose homeostasis, MHT also produced beneficial effects on important CVD risk factors, such as blood pressure, LDL cholesterol, triglycerides, lipoprotein(a), adhesion and coagulation molecules 10,13. However, population-based studies regarding the effect of MHT exposure, and timing of MHT use (i.e., time-since-menopause) 4 on CVD outcomes among women with T2DM are virtually none. Black women are disproportionately likely to be treated with premenopausal hysterectomy with oophorectomy, therefore, undergo surgical menopause 14,15. However, despite a higher rate of early menopause, more severe vasomotor symptoms 16,17, and higher postmenopausal cardiovascular burden than white women 18, research about the effect of MHT on cardiovascular outcomes in black women, especially among those with compromised glucose metabolism, has been historically lacking 5,19. Whether MHT is a safe option for women with pre-diabetes (PreDM) or T2DM to manage their vasomotor symptoms and whether there is a racial difference regarding the effect of MHT on CVD risk warrant further research. The objective of this study was to examine the association between ever use or early initiation of MHT and CVD risk in postmenopausal women with PreDM or T2DM by race, using three large prospective CVD cohorts.

2. Materials and methods

2.1. Study population

This study pooled data from three prospective CVD cohorts: the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Jackson Heart Study (JHS). ARIC is a prospective epidemiologic study that enrolled 15,792 adults 45 to 64 years of age from 4 U.S. communities, including Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland 20,21. MESA is a population-based study that enrolled 6,815 adults 45 to 84 years of age, from 6 U.S. communities, which included Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; New York, New York; and St. Paul, Minnesota 22. JHS is a single-site community-based study of African American adults recruited from Jackson, Mississippi 23. Detailed methods of each cohort’s study design, recruitment strategy, and visit protocols have been described previously 20–23 (also summarized in Supplemental table 1). The de-identified data were acquired from the National Heart, Lung and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). This included data from ARIC visit 1 through visit 5 (1987–2013), MESA visit 1 through visit 5 (2000 to 2011), and JHS visit 1 through visit 3 (2000–2013). Written informed consent was provided by participants for the original three studies. In this analysis, we included postmenopausal women ≥45 years of age, with PreDM or T2DM, with available data on MHT use, and with follow-up for CVD events. Participants with unknown T2DM status or glucose level, with pre-existing CVD, or with missing CVD follow-ups were excluded. This secondary analysis involved existing de-identified data do not require review from the Tulane University Institutional Review Board.

2.2. Measurements

2.2.1. Postmenopausal status, MHT use and menopausal type

At the baseline of ARIC and JHS, women were asked, “Have you had any menstrual periods during the past 2 years?” and “Have you reached menopause?”. Women who had not had a menstrual period within the previous 2 years were classified as “postmenopausal.” 24,25. Women were also asked, “Have you ever taken female hormone pills, shots, or implants, not including birth control pills?”. Those who answered “yes” were coded as ‘ever used MHT’. “Age at last menstrual period” and “At what age did you start taking this hormone for the first time” were used to categorize early use of MHT (≤5 years since menopause). At MESA baseline, women were asked if they had gone through “menopause” and required to state the age at which they experienced menopause. Women who reported that they were going through menopause at baseline were asked to provide the date of their last menstrual period and the number of periods they had experienced in the last twelve months. Women who did not experience menstruation for twelve or more months before baseline were classified as being “postmenopausal” 26. Women were also asked, “Have you ever taken hormone replacement therapy?” and “At what age did you begin?”. These questions were used to categorize “ever use of MHT” and “early use of MHT”, respectively in MESA. Among postmenopausal women in all cohorts, those who reported menstrual cessation due to bilateral oophorectomy or radiation were classified as having surgical menopause, whereas those who reported cessation of menstrual bleeding that was not preceded by oophorectomy or radiation were classified as having natural menopause.

2.2.2. PreDM and T2DM

For all three cohorts, PreDM was defined as a measured fasting glucose of 100 to 125 mg/dL or hemoglobin A1c 5.7–6.4%. T2DM was defined as a self-reported physician’s diagnosis, current insulin, or hypoglycemic medication use, a measured fasting glucose of ≥126 mg/dL, or hemoglobin A1c ≥6.5% 27–29.

2.2.3. CVD outcome definitions and ascertainments

For all three cohorts, incident CHD was defined as a myocardial infarction (MI), CHD death, or cardiac procedure (percutaneous coronary interventions, bypass surgery, or coronary revascularization). Stroke was defined as an ischemic stroke. Incident atherosclerotic cardiovascular disease (ASCVD) was defined as a MI, CHD death, cardiac procedure (above mentioned), or ischemic stroke. The adjudication process for events involved a panel to review hospitalization and death data per study protocols previously reported for all three cohorts 22,30,31. All events were adjudicated from medical records and death certificates for end-point classification.

2.2.4. Covariates

We included baseline age, race/ethnicity (non-Hispanic White [white] or non-Hispanic Black [black]), education attainment, smoking status, use of antihypertensive medications, and lipid lowering medications. This information was collected using standard questionnaires from three studies. We also included baseline health indicators, including blood pressure, total cholesterol, and body mass index (BMI), menopausal type (surgery induced vs naturally occurred), and menopausal age. Detailed measurement procedures for the ARIC, MESA and JHS can be found in previous publications 22,30,31.

2.3. Analysis

From an original 25,725 participants (ARIC: 15,028, MESA: 6,814, and JHS: 3,883), we excluded men, women with pre- or perimenopause, and ARIC and JHS overlap participants. Among postmenopausal women, we further excluded women with prevalent CVD, those with missing key covariates, T2DM or PreDM, or MHT use, those with missing CVD outcomes, or non-T2DM or non-PreDM. We included a total number of 2,917 postmenopausal women with T2DM or PreDM eligible for analysis. A detailed sample selection process from the cohorts, individually and overall, is displayed in Supplemental figure 1.

Chi-square tests and ANOVA were used to compare the differences of characteristics between racial groups in the study. Crude incidence was assessed by Poisson regression. The associations between ever or early use of MHT and CVD outcomes were examined in Cox proportional hazards models. Multivariable analysis adjusted for age, race, cohort indicator, smoking status, blood pressure, total cholesterol, BMI, antihypertensive medication, lipid lowering medication, menopausal type, and menopausal age. We fit our models to the event of interest (CHD, stroke, or ASCVD) or censoring (lost of follow-up or end of study) times of all participants. All analyses were performed in the overall sample first then stratified by race. We tested the interaction between ever or early use MHT and race by adding two terms ‘ever use MHT × race’ or ‘early use MHT × race’ in the models. p<0.05 indicates statistical significance for the interaction. As secondary analyses, we conducted the same analyses among surgical menopausal women only, and in PreDM and T2DM subjects, separately. All analyses were performed using SAS (9.4; SAS institute, Cary, NC).

3. Results

Table 1 shows the descriptive characteristics of the pooled cohorts. Mean age was 59 years. More than 60% of women had less than high school education. Compared to black women, white women were more likely to be current cigarette smokers, to have elevated total cholesterol level, and to take lipid lowering medication. In comparison to white women, black women were more likely to be obese, to be hypertensive, to have fasting glucose over 126 mg/dL, to take antihypertensive medication, to reach menopause earlier, to undergo surgical menopause, and to use MHT at a younger age.

Table 1.

Baseline characteristics of postmenopausal women with prediabetes or type 2 diabetes by race

All (n=3,213) Non-Hispanic white (n=1,479) Non-Hispanic black (n=1,438) p-value
Age (mean ± SD†, years) 58.8 ± 7.8 58.4 ± 6.0 57.6 ± 8.3 0.002
≤High school education, n (%) 1968 (61.3) 939 (63.5) 806 (56.2) <0.0001
Current smoking, n (%) 592 (18.4) 328 (22.2) 249 (17.3) 0.0001
BMI ‡
 BMI (mean, kg/m2) 30.6 ± 6.6 28.6 ± 5.8 32.9 ± 6.6 <0.0001
 BMI≥30, n (%) 1559 (48.6) 521 (35.3) 905 (63) <0.0001
Blood pressure
 SBP§ (mean, mmHg) 128.8 ± 20.9 124.5 ± 19 132.0 ± 21.4 <0.0001
 DBP (mean, mmHg) 73.0 ± 10.8 70.8 ± 10.3 76.1 ± 10.8 <0.0001
 SBP≥140; DBP≥90 mmHg, n (%) 1411 (43.9) 585 (39.6) 717 (49.9) <0.0001
Cholesterol
 Total cholesterol (mean, mg/dL) 218.4 ± 44.5 227.0 ± 44.4 213.4 ± 44.9 <0.0001
 Total cholesterol≥200 mg/dL, n (%) 2024 (64.3) 1071 (72.5) 821 (59.8) <0.0001
Fasting glucose
 Fasting glucose (mean, mg/dL) 130.8 (55.9) 122.6 (44.7) 141.3 (44.8) <0.0001
 100–125, n (%) 2202 (76.8) 1206 (81.6) 996 (71.6) <0.0001
 126–211, n (%) 446 (15.5) 197 (13.3) 249 (17.9)
 ≥212, n (%) 221 (7.7) 75 (5.1) 146 (10.5)
Antihypertensive medication, n 1498 (46.7) 496 (33.5) 846 (59.0) <0.0001
Lipid lowering medication, n (%) 1019 (31.9) 507 (34.4) 440 (30.9) 0.05
Menopausal age (mean ± SD, years) 44.8 ± 7.3 46.0 ± 6.2 43.0 ± 8.2 <0.0001
Menopausal type, n (%)
 Natural 1829 (57.8) 997 (69.1) 609 (42.7) <0.0001
 Surgical 1300 (41.1) 436 (30.2) 797 (55.9)
 Not specified 35 (1.1) 9 (0.6) 20 (1.4)
Ever used MHT (yes), n (%) 1200 (37.4) 561 (37.9) 533 (37.1) 0.75
Age starting MHT∥ in current users# (mean ± SD, years) 46.9 ± 9.3 47.4 ± 8.6 45 ± 9.3 <0.0001
Time of initiating MHT in current users, n (%)
≤5 years since menopause 746 (72.3) 341 (71.9) 348 (76) 0.13
6–10 years since menopause 117 (11.3) 59 (12.5) 39 (8.5)
>10 years since menopause 169 (16.4) 74 (15.6) 71 (15.5)
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†

SD: standard deviation

‡

BMI: body mass index

§

SBP: systolic blood pressure

DBP: diastolic blood pressure

∥

MHT: menopausal hormone therapy.

#

N for current MHT user: 1032. Covariates missing n: education 4; smoking 1; BMI 2; blood pressure 2; total cholesterol 65; 48 fasting glucose, antihypertensive medication 5; lipid lowering medication 18; menopausal age 123; menopause type 49.

During a median follow-up of 15 years for 2,917 postmenopausal women with PreDM or T2DM, 264 stroke, 484 CHD and 659 ASCVD events were observed. Crude event rates for stroke, CHD, and ASCVD were not significantly different between ever or early use of MHT group vs never use of MHT group, overall and in the white women group (Figure 1). In black women, when comparing incident rates of never, early, or late users of MHT, those who had never used MHT had the highest rates, whereas late users had the lowest rates of stroke, CHD, and ASCVD (p-values <0.05) (Figure 1).

Figure 1.

Figure 1.

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Crude incident rates of stroke, CHD, and ASCVD (per 1000-year).

The adjusted association between ever MHT use and CVD risk in women with PreDM or T2DM was assessed in the overall sample and by race (Figure 2). Interaction terms of ‘ever use MHT × race’ and ‘early use of MHT × race’ for outcomes of stroke, CHD and ASCVD had p-values ≤0.08. Ever or early use of MHT was significantly associated with reduced risk of stroke compared to never use MHT in white women with PreDM or T2DM (hazard ratio [HR], 95% confidence interval [CI]: 0.86, 95% CI [0.76–0.98] and 0.82 [0.72–0.95], respectively]. However, there was no significant association between ever or early use of MHT and stroke risk in black women. Similarly, ever or early use of MHT was significantly associated with reduced risk of CHD [0.86, (0. 76–0.98) and 0.85 (0.74–0.98), respectively] and ASCVD [0.83 (0.73–0.95) and 0.82 (0.7–0.96), respectively] compared to never use MHT in white women with PreDM or T2DM (Figure 2).

Figure 2. Adjusted hazard ratios of ever or early use (vs never use) of MHT and risk of stroke, CHD, and ASCVD in women with PreDM or T2DM.

Figure 2.

Figure 2.

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HRs were adjusted for age, race, cohort indicator, smoking status, blood pressure, total cholesterol, BMI, antihypertensive medication, lipid lowering medication, menopausal type, and menopausal age (only for model of ever use MHT and ASCVD).

*P<0.05

P-values for interaction terms ‘ever use MHT × race’ in models for stroke, CHD, and ASCVE ≤ 0.03.

P-values for interaction terms ‘early use MHT × race’ models for stroke, CHD, and ASCVE ≤ 0.08.

To address the potential confounding by racial disparities in prevalence of surgical menopause, we also assessed the effect of MHT among participants who underwent surgical menopause only (n=1,300). In this subpopulation, ever or early use of MHT was significantly associated with CVD risk reduction in white women, and the effect of MHT was greater than of in the overall sample. In the white group, HRs of ever vs never use of MHT for stroke, CHD, and ASCVD were 0.66 (0.53–0.82), 0.73 (0.58–0.91), and 0.65 (0.51–0.82), respectively; HRs of early vs never use of MHT for three outcomes were (0.62, [0.48–0.78]), CHD (0.69 [0.54–0.88]), and ASCVD (0.6 [0.47–0.79]), respectively. The effect of MHT use was null in black women with PreDM or DM who underwent surgical menopause (Supplemental figure 2). We also performed the analysis in PreDM and T2DM subjects separately. Results in two groups were similar with the main findings that is in white women, ever or early use of MHT appeared to be associated with reduced risk of CVD. The risk reduction was statistically significant on stroke in PreDM and T2DM groups (Supplemental figure 3A and B).

4. Discussion

Our first finding is that any exposure to MHT is associated with a small but statistically significant ASCVD risk reduction in white women with PreDM or DM. To our knowledge, this is the first study to show a negative association between use of MHT and CHD or stroke risk among white women with PreDM or DM. The initial Women’s Health Initiative (WHI) study, including women aged 50 to 79 years and disregarding time since menopause, reported increased CHD risk associated with use of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) 1. However, when women were stratified by age, or time since menopause, the increased risk of CHD was not significant in younger women or when MHT was initiated within 10 years of menopause 32. In the CEE alone arm, there was no increase in CHD risk compared to placebo, but the risk for non-fatal stroke was elevated before stratifying by age 33. After age stratification, women in the 50–59 years age range, who were randomized to CEE alone, had significant reductions in CHD of 41%, total MI of 46% and total mortality of 27% compared to placebo 34. The more recent WHI analysis with longer follow up concluded null effect of MHT use on CVD risk or mortality 2,34. With respect to secondary prevention, MHT did not appear to provide any benefit (or risk) in women with established CVD from the Heart and Estrogen/progestin Replacement Study (HERS). After a mean follow-up of 4 years, the risk for MI or CHD death did not differ between the CEE plus MPA versus the placebo group 8. Meta-analyses of RCTs showed that in women who initiated MHT less than 10 years since menopause or younger than 60 years of age, exhibited 32% reduction in CHD relative to placebo 10,35,36. The magnitude of CHD reduction appeared to be similar among RCTs and observational studies of women who initiated MHT at or near the time of menopause 37. In contrast, the effect of MHT on CHD and total mortality is null when MHT is initiated after 10 years since menopause or in women older than 60 years of age. These studies led to the current recommendations that MHT should be initiated in women < 60 years of age and within 10 years of menopause onset 38,39. However, because of the small number of women with PreDM or T2DM in clinical trials, it is unclear if MHT is an option for this group of women to manage moderate to severe vasomotor symptoms. The observed beneficial effect of CVD associated with MHT in white women with PreDM or DM indicated a possible safe use of MHT in this group but warranted more clinical research to further clarify the balance of risks and benefits.

We identified a modifying effect of race in the association between MHT use and risk of stroke, CHD or ASCVD. Contrary to the reduced CVD risk associated with ever or early use of MHT in white women with PreDM or DM, we did not find these associations to be significant in the black group. Studies on the effect of MHT on stroke or CHD among black women are limited. In the WHI estrogen alone trial, no increase in CHD was seen for black women during intervention or post-intervention follow-up period 40,41. Similarly, no significant elevation of stroke risk was observed in the intervention period for black women as well 42. When comparing crude incidence rates in our study, among black women, late MHT users had the lowest rates of stroke, CHD, or ASCVD, which appeared to suggest a protective effect of late use of MHT in comparison to never use or early use. However, when confounders were taken into account, we saw a null association between late use of MHT in comparison to never use or early use across all outcomes. The null findings in black women with PreDM or DM may be due to their suboptimal cardiometabolic profiles compared to white women (i.e., higher proportion of obesity, hypertension, and fasting hyperglycemia), which may have mitigated the beneficial effect of MHT in their long-term cardiovascular outcomes. Other mechanisms, such as racial difference in reproductive hormone metabolism and/or in effect of estrogen receptors in cardiovascular disease 42,43 may also help shed lights on the racial divergence in MHT effect and are worthy of further examinations.

4.1. Strengths and limitations

The strengths of the study include the use of three large and well-characterized multiethnic cohorts, which provides an opportunity to investigate the effect of MHT and use of MHT on CVD risk in postmenopausal women with PreDM or T2DM. Previous studies excluded such participants or had a small number of participants for such examinations 1,7,8. We were also able to stratify the analysis by major racial groups and demonstrate racial differences regarding MHT use, timing of using MHT and CVD risk among middle-aged and older women with a long follow up time (median follow up was 15 years). Other major studies on MHT, on the other hand, were mostly white 8,19,32, included women beyond the age that seeks MHT (e.g., average age in WHI was 63 years, HERS 67 years) 8,32, and with shorter follow up time 8,44. Additionally, the three cohorts included standardized evaluation of risk factors and ascertainment of CVD events that were adjudicated by end points committees. Moreover, the participant level data from the established CVD cohorts enabled us to harmonize variables using common definitions, coding, and cutoff points, which is superior to meta-analysis using published aggregated results. However, the study is also subject to limitations. We did not include MHT type in our analysis, as previous studies of ARIC, MESA or JHS found participants who reported MHT use were predominantly estrogen-only therapy users 25,45. While we lacked data regarding the route of estrogen administration, before 2002, the pre-WHI era when ARIC, MESA and JHS were initiated, over 75% of estrogen replacement was oral 46. Therefore, our findings, to a large extent, may reflect the effect of oral estrogen-only therapy on risk of CVD among women with PreDM or T2DM. Nevertheless, we acknowledge the limitation of this observational study which is based on the three parent cohorts that did not collect detailed information on the MHT type, dosage, and administration route. We therefore cannot clearly distinguish the effect of these factors in the analysis. Clinical trial studies may have such information; however, they usually excluded women with abnormal glucose metabolism. Additionally, it is likely that our study participants who were enrolled from late 80s to late 90s and used MHT at baseline may have stopped using MHT during follow up. However, we expected the discontinuation of MHT would possibility bias our findings towards the null. Moreover, a portion of T2DM cases in our analysis were selected based on self-reported diagnosis therefore subject to information bias (e.g., self-reporting bias, recall bias) 47.Finally, this analysis is based on observational studies, which are unable to establish casual inferences.

4.2. Conclusions

Ever or early use of MHT was associated with statistically significant reduced risk of stroke, CHD, and ASCVD in white women with PreDM or T2DM. This finding did not support to use of MHT for CVD prevention. Our findings indicate the possibility of using MHT in women with PreDM or T2DM to manage moderate to severe vasomotor symptoms. Clinical trials or large prospective cohort studies purposefully testing the effect of MHT on CVD and other health outcomes, clarifying the effect by formulation, dosages, administration routes, and timing and length of use in individuals with PreDM or DM, are needed. Future studies should also consider including a sufficient number of racial minority women to support robust racial stratified examinations.

Supplementary Material

1
2
3
4

  • The effect of menopausal hormone therapy (MHT) on cardiovascular disease (CVD) outcomes in women with type 2 diabetes (T2DM) is mostly lacking due to no or limited inclusion of participants with T2DM in clinical studies.

  • Pooled data from three landmark prospective CVD cohorts in the United States, the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA) and the Jackson Heart Study (JHS), showed that ever use and early use of MHT was associated with reduced risk of stroke, coronary heart disease (CHD), and a composite atherosclerotic cardiovascular disease (ASCVD) in women with pre-diabetes or T2DM.

  • Race may be an effect modifier to the association between MHT use and risk of CVD as the reduced risk of stroke, CHD or ASCVD was only evident in White women with pre-diabetes or T2DM.

Acknowledgments

The authors thank other investigators, the staff, and the participants of the ARIC, MESA, and JHS for their contribution. We also thank the staff of the National Heart, Lung and Blood Institute BioLINCC for their coordination for our data access.

Financial support

This project was supported by a grant (NIH K12HD043451) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Scholar. FMJ was supported by NIH grants (DK107444 and DK074970), a U.S. Department of Veterans Affairs Merit Award (BX003725), and the Tulane Center of Excellence in Sex-Based Biology & Medicine. AHA was supported by NIH grants (R01DK104730, R01DK107566, and P20GM109036) and the Tulane University Translational Science Institute.

Footnotes

The authors have no conflict of interest to disclose.

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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1
NIHMS1778204-supplement-1.pdf (571.3KB, pdf)
2
NIHMS1778204-supplement-2.pptx (134.8KB, pptx)
3
NIHMS1778204-supplement-3.pptx (234.4KB, pptx)
4
NIHMS1778204-supplement-4.docx (15KB, docx)

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