Reproductive History and Hormonal Birth Control Use Are Associated with Coronary Calcium Progression in Women with Type 1 Diabetes Mellitus

Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 06/2008; 93(6):2142-8. DOI: 10.1210/jc.2007-2025
Source: PubMed


Coronary artery disease is increased in women with type 1 diabetes (T1D), compared with nondiabetic (Non-DM) women. Women with T1D have more menstrual dysfunction and are less likely to use hormonal birth control (BC) than Non-DM women.
The purpose of this study was to determine whether coronary artery calcium (CAC) is associated with menstrual dysfunction and BC use in women with T1D.
This was a prospective cohort study, and participants were followed up for an average of 2.4 yr.
Patients included 612 women (293 T1D, 319 Non-DM) between the ages of 19 and 55 yr who had CAC measured twice by electron beam tomography.
Irregular menses and amenorrhea were more common in T1D than Non-DM women (22.1 vs. 14.9%, P < 0.05 and 16.6 vs. 7.0%, P < 0.001). T1D women reported less BC use than Non-DM women (79.8 vs. 89.9%, P < 0.001) and reached menarche at an older age (13.1 +/- 1.8 vs. 12.8 +/- 1.5 yr, P < 0.05). Use of BC was associated with less CAC progression in all women, but this association was stronger in T1D women (P value for interaction = 0.02). Irregular menses were associated with greater CAC progression only among T1D women.
A prior history of BC use is associated with reduced CAC progression among all women, with a stronger association in T1D than in Non-DM women. Women with T1D who report irregular menses have increased CAC progression, compared with those with regular menses.

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    • "One study suggested that women with type 1 diabetes are at risk to experience early depletion of the ovarian follicle pool, resulting in menopause at a younger age compared with women without diabetes (Dorman et al., 2001), although this observation was not supported by later reports (Sjoberg et al., 2011; Kim et al., 2014). Women with type 1 diabetes are reported to have a delayed age at menarche (Rohrer et al., 2007) and are at higher risk for menstrual irregularities (Codner et al., 2006; Snell-Bergeon et al., 2008) compared with women without diabetes of similar age. Combined with an earlier age at menopause, these women may be subjected to a 6-year reduction in reproductive years (Dorman et al., 2001). "
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    ABSTRACT: Is type 1 diabetes a determinant of advanced ovarian ageing, resulting in an early age at natural menopause? No clear evidence was provided that type 1 diabetes is a determinant of accelerated ovarian ageing resulting in an early menopause. The association between type 1 diabetes and early menopause has been examined previously with inconsistent results. A cross-sectional study was performed in 140 post-menopausal women with, and 5426 post-menopausal women without, diabetes. Both women with and without diabetes had experienced natural menopause. Study participants filled out a standardized questionnaire including report of their age at last menstrual period. Differences in menopausal age were analysed using linear regression analyses, with adjustment for possible confounders. Mean age at natural menopause was 49.8 ± 4.7 years in women with type 1 diabetes and 49.8 ± 4.1 in women without diabetes. Linear regression analyses showed that type 1 diabetes was not associated with an earlier menopause compared with the reference group without diabetes, after adjustment for age, smoking history and parity (difference in age at menopause between women with type 1 diabetes and reference group 0.34 years, 95% confidence interval -0.34, 1.01). Age at menopause was self-reported and assessed retrospectively. We had no information regarding microvascular complications therefore a possible association between vascular health and menopausal age could not be investigated. It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes. The EPIC-NL study was funded by the 'Europe against Cancer' Program of the European Commission (SANCO), the Dutch Ministry of Public Health, Welfare and Sports, the Dutch Cancer Society, the Netherlands Organisation for Health research and Development (ZonMW), and World Cancer Research Fund (WCRF). F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors, and Roche. Not applicable. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
    Human Reproduction 12/2014; 30(2). DOI:10.1093/humrep/deu327 · 4.57 Impact Factor
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    • "Subjects were asked to recall their age at the time of their first menstrual period. Probing questions were asked to help the subjects if they had difficulty remembering the exact age, such as remembering the season, grade or proximity to a birthday [32]. An Insulin Record Questionnaire was used to collect insulin regimen and dose. "
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    ABSTRACT: Menarche delay has been reported in adolescent females with type 1 diabetes (T1DM), perhaps due to poor glycemic control. We sought to compare age at menarche between adolescent females with T1DM and national data, and to identify factors associated with delayed menarche and menstrual irregularity in T1DM. This was a cross-sectional study and females ages 12- 24 years (n = 228) with at least one menstrual period were recruited during their outpatient diabetes clinic appointment. The National Health and Nutrition Examination Survey (NHANES) 2001-2006 data (n = 3690) for females 12-24 years were used as a control group. Age at menarche was later in adolescent females with T1DM diagnosed prior to menarche (12.81 +/- 0.09 years) (mean+/- SE) (n = 185) than for adolescent females diagnosed after menarche (12.17 0.19 years, p = 0.0015) (n = 43). Average age of menarche in NHANES was 12.27 +/- 0.038 years, which was significantly earlier than adolescent females with T1DM prior to menarche (p < 0.0001) and similar to adolescent females diagnosed after menarche (p = 0.77). Older age at menarche was negatively correlated with BMI z-score (r = -0.23 p = 0.0029) but not hemoglobin A1c (A1c) at menarche (r = 0.01, p = 0.91). Among 181 adolescent females who were at least 2 years post menarche, 63 (35%) reported usually or always irregular cycles. Adolescent females with T1DM had a later onset of menarche than both adolescent females who developed T1DM after menarche and NHANES data. Menarche age was negatively associated with BMI z-score, but not A1c. Despite improved treatment in recent decades, menarche delay and high prevalence of menstrual irregularity is still observed among adolescent females with T1DM.
    Reproductive Biology and Endocrinology 05/2011; 9(1):61. DOI:10.1186/1477-7827-9-61 · 2.23 Impact Factor
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    • "That estrogens may play a role in these phenomena is supported indirectly by the observation that oral contraceptive exposure inhibits atherosclerosis in subordinate monkeys (Kaplan et al., 1995). Furthermore, although the effects of oral contraceptive use on heart disease are still not known with certainty, reduced calcium content and reduced stenosis in the coronary arteries have been observed in women taking these compounds (Merz et al., 2006; Snell-Bergeon et al., 2008). "
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    ABSTRACT: Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.
    Human Reproduction 10/2010; 25(12):3083-94. DOI:10.1093/humrep/deq288 · 4.57 Impact Factor
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