HES 383 - Physical Dimensions of Aging PDF

HES 383 – PHYSICAL DIMENSIONS OF AGING September 19, 2023 Reproductive Aging Prof Gina Whitaker, BSc Kin, PhD The UBC Okanagan Campus and the City of Kelowna are located on the traditional, ancestral, and unceded territory of the Syilx Okanagan Nation. NORMAL PHYSIOLOGICAL CHANGES OVER ONE MENSTRU...

HES 383 – PHYSICAL DIMENSIONS OF AGING September 19, 2023 Reproductive Aging Prof Gina Whitaker, BSc Kin, PhD The UBC Okanagan Campus and the City of Kelowna are located on the traditional, ancestral, and unceded territory of the Syilx Okanagan Nation. NORMAL PHYSIOLOGICAL CHANGES OVER ONE MENSTRUAL CYCLE • Females are born with full supply of follicles ~750 000. Down to 250 000 by puberty. Each follicle contains 1 egg • Every cycle (approx. 28 days), one mature egg is released from the growing follicle (Ovulation) • This cycle is regulated by hormones LH & FSH are released from the pituitary gland + - Follicle growth and prep for ovulation - Estrogen & Progesterone production and secretion into the blood by the ovaries Estrogen & Progesterone functions (specific to menstrual cycle): - Stimulate ovulation (mainly Estrogen) - Prepare the uterus for implantation of a fertilized egg - Negative feedback to pituitary gland  inhibits LH and FSH secretion If no fertilization: Es & Pg levels fall and thickened layer of uterus (endometrium) is sloughed off. LH & FSH levels rise and cycle begins again ESTROGEN ALSO PLAYS AN IMPORTANT ROLE IN • Bone strength and structure • Muscle mass, strength and power • Cardiovascular protection • Brain health and cognitive function ESTROGEN’S PROTECTIVE EFFECT ON THE CARDIOVASCULAR SYSTEM Iorga, A., Cunningham, C. M., Moazeni, S., Ruffenach, G., Umar, S., & Eghbali, M. (2017). The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biology of sex differences, 8(1), 33. https://doi.org/10.1186/s13293-017-0152-8 RELATIONSHIP BETWEEN ESTROGEN AND ACL RUPTURE IN A NORMAL MENSTRUAL CYCLE  Estrogen responsible for joint laxity in women Front. Physiol., 15 January 2019 https://doi.org/10.3389/fphys.2018.01834 AGING & FEMALE REPRODUCTIVE CHANGES • Oocyte number and quality decline progressively • Approaching Menopause: • Variable Estrogen & Progesterone • Increased LH and FSH (eventually declines in later years) • Decline in Anabolic Hormones alongside these changes • Decreased Growth Hormone • Decreased IGF-1 Chidi-Ogbolu, N., & Baar, K. (2019). Effect of estrogen on musculoskeletal performance and injury risk. Frontiers in physiology, 9, 1834. REVISED STRAW CRITERIA FOR CLASSIFICATION OF MENOPAUSAL TRANSITION The STRAW model divides reproductive life into 7 stages - Reproductive years (early, peak, late) - Transition years (early and late menopausal transition - MT) - Post-menopause (early and late)  Entry into MT at ~ 46 - Increased FSH, variable estrogen, progesterone decline - Variable cycle length (early MT) - Amenorrhea of > 60d (late MT)  Menopause onset at Final Menstrual Period (FMP) - Follicle number approaches 0 - Ave age 52 YO (range: 40 – 60YO) STRAW: Stages of Reproductive Aging Workshop PHYSIOLOGICAL CHANGES ASSOCIATED WITH MENOPAUSE • Decreased Estrogen  THIS IS THE HALLMARK OF MENOPAUSE • Uterus shrinks (up to 70% 15 – 20 years postmenopause) • Vaginal atrophy – smaller, thinner lining, decreased lubrication • Bone resorption > formation • Decline in proportion of lean body mass and increase in fat mass • Shift of fat distribution: Increased proportion of fat in Abdominal and Visceral region (vs. hips and limbs) MENOPAUSE AND BONE LOSS • Accelerated bone loss occurs just prior (~1 year) to FMP and continues for the first 2 years years after • Driven by decreases in Estrogen and increases in FSH levels.  Estrogen inhibits osteoclast activity and stimulates osteoblast activity. So when estrogen decreases at FMP: bone resorption > bone formation Osteoblasts  build bone Osteoclasts  break down bone • Prevention: - Ca2+ and vit D intake - Weight-bearing & resistance exercise - Hormone replacement therapy* MENOPAUSE AND DECLINE IN MUSCLE MASS AND STRENGTH Maltais ML, Desroches J, Dionne IJ. Changes in muscle mass and strength after menopause. J Musculoskelet Neuronal Interact. 2009;9(4):186–197. PHYSICAL PERFORMANCE ACROSS MENOPAUSAL STAGES Compared to premenopausal women, post-menopausal women had: - Decreased knee extension strength (isometric) - Decreased hand grip strength (isometric) - Decreased vertical jumping height Bondarev D, Laakkonen EK, Finni T, et al. Physical performance in relation to menopause status and physical activity. Menopause. 2018;25(12):1432–1441. doi:10.1097/GME.0000000000001137 POSSIBLE SYMPTOMS DURING PERI-AND POST-MENOPAUSE 4 out of 5 females experience psychological and/or physical symptoms around the time and after menopause • Vasomotor Symptoms (hot flashes & night sweats) – most common symptom by far (up to 80% of women) • Mental Health – depression, anxiety • Sleep Disturbance – getting to sleep and staying asleep • Cognitive Performance – menopause-related difficulties are temporary and during perimenopause (resolves post-menopause) • Sexual Function – decreased libido, intensity of arousal, increased risk of pain during intercourse • Weight gain CHANGES IN BODY COMPOSITION & BODY WEIGHT OVER THE YEARS OF MENOPAUSAL TRANSITION This increase in fat mass was consistent across all centrally measured locations. A decrease was measured in total leg fat percentage.  suggests a shift to central fat accumulation Model-predicted trajectories of body composition and body weight outcomes relative to the time prior to or after the FMP, SWAN. Values shown are for an average study participant. Greendale GA, et. al. Changes in body composition and weight during the menopause transition. JCI Insight. 2019 Mar 7;4(5):e124865. doi: 10.1172/jci.insight.124865 MENOPAUSE AND HEALTH RISKS With menopause, studies show an increased risk of: • Cardiovascular disease • (loss of protective effects of estrogen) • Increased cholesterol and triglyceride levels • Increased visceral adipose around the heart • Type 2 diabetes • Decreased insulin sensitivity • Metabolic Syndrome • Low bone mineral density (Osteopenia) and Osteoporosis • Genitourinary Syndrome of Menopause • Urinary incontinence, other bladder issues, vaginal discomfort, impaired sexual function PHYSICAL ACTIVITY POST-MENOPAUSE • Most menopausal and post-menopausal women do not meet recommended PA guidelines (CSEP) • Exercise cannot delay menopause • Not enough evidence to show exercise effect on vasomotor symptoms • PA benefits: • Improved Sleep • Improved Mood • Prevention of weight gain • Maintenance of Bone Mineral Density • Maintenance of muscle strength • CVD and T2D prevention C AN THE MENOPAUSE-ASSOCIATED DECLINE IN MUSCLE MASS AND STRENGTH BE PREVENTED WITH EXERCISE? • Estrogen promotes the anabolic response of muscle cells to exercise  muscle growth A decline in estrogen results in a decreased ability to ‘build’ muscle (anabolic resistance) • Goal is to: • Enter into menopausal years in optimal health • Maintain function throughout menopause by focusing on modifiable factors EXERCISE PRESCRIPTION FOR FEMALES POST-MENOPAUSE Should include: • Resistance exercises – to maintain/minimize decline in muscle mass & strength • Weight-bearing activities & resistance training – to minimize bone loss • Aerobic activity – to maintain CV fitness, and more… • Flexibility and balance training There are no specific guidelines for post-menopause (other than the CSEP 24h movement guidelines for Older Adults) • Some evidence that higher-intensity aerobic exercise and increasing frequency of resistance to 3x per week is ideal for menopause symptoms and risk factor prevention • Preliminary study results show significant benefit in fat reduction with aerobic intensity at 40-80% VO2max for >30 minute durations in postmenopausal women HORMONE THERAPY • Estrogen or Estrogen + Progesterone • Used to be the best practice to prescribe this to post-menopausal women with symptoms • Now, not used as widely, due to cons > pros • Studies have shown increased risk of breast, ovarian, uterine cancers, heart events, stroke, blood clots and dementia with long term use of hormone therapy. • Pros: effective treatment for vasomotor symptoms, prevention of bone loss, some cardioprotection at first • Current recommendations (2017): Risk-benefit ratio is favorable if prescribed to under 60YO, within 10 years of FMP and if the individual is otherwise healthy (e.g. no CVD) Re-evaluate risk-benefit ration after 5 years on HRT “A simple blood test had revealed that I carried a mutation in the BRCA1 gene. It gave me an estimated 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. I lost my mother, grandmother and aunt to cancer.” • Double mastectomy • Laparoscopic bilateral salpingooopherectomy REPRODUCTIVE AGING IN MEN • Fertility declines slightly • Lower total sperm count per ejaculate • Decreased motility of sperm • Increased risk of genetic abnormalities in offspring • Miscarriage, genetic diseases, complex neuro/psychiatric conditions, childhood cancers  Overall decline in sperm quality (decline begins as early as 30-35YO) • • • • Decreased testosterone levels Decreased size and weight of testes Prostate gland enlarges and some of prostate tissue is replaced with scar tissue Increased risk of erectile dysfunction TESTOSTERONE • Secreted by the Testes • Circulates in the blood • 60% tightly bound to sex hormone binding globulin (SHBG)  Testosterone is not bioavailable when bound to SHBG • 38% loosely bound to albumin (bioavailable) • 2% free in the blood (bioavailable and biologically active) • Function in the body • Androgenic effects: development and maintenance of sex organs, sperm development, arousal, secondary sex characteristics (deep voice, hair growth) • Anabolic effects: build muscle mass and strength, bone density and strength DECREASES IN TESTOSTERONE WITH AGE • Total circulating Testosterone levels peak in 30s and then decline 0.3-1.8% per year (accelerates after 75YO) • Decline is mainly due to decrease in number of Leydig cells of the testes • Also get an increase amount of testosterone bound to SHBG (so even less available for use). Corresponds to more rapid decline in free testosterone. (LH = luteinizing hormone: stimulates Testosterone release from Leydig cells) • Most men do not experience clinically noticeable side effects of testosterone decline • Low testosterone is linked to increased risk of: • Hypertension • Dyslipidemia • Obesity • Type 2 diabetes • Cardiovascular disease • Dementia • Prostate Cancer • Overall Mortality LATE-ONSET HYPOGONADISM (LOH) • A syndrome that is characterised by low testosterone + accompanying signs and/or symptoms • European Male Aging Study: • 23.5% of community-dwelling men (40 – 70 YO) had clinically low testosterone levels • Only 2.1% had symptoms Main symptoms & signs of LOH in men INCREASED BMI IS ASSOCIATED WITH LOWER TESTOSTERONE The trajectory of age-related decline in testosterone is affected by: • Adiposity – Overweight & Obesity **Strongest factor • Medications • Smoking • Alcohol • Stress • Diet (high fat, low fiber) • Genetics WEIGHT GAIN/LOSS AND EFFECT ON TESTOSTERONE Camacho EM, et.al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013 Feb 20;168(3):445-55. doi: 10.1530/EJE-12-0890. EFFECT OF EXERCISE ON TESTOSTERONE LEVELS IN OLDER MEN • Increased levels of exercise in males are associated with lower likelihood of having low testosterone. • Mixed results in research on short-term interventions • Some studies of aerobic exercise interventions have shown an increase in total and free testosterone • Some studies show an increase in bioavailable testosterone with resistance training • More promise recently shown with high-intensity interval training Hayes, L. D., & Elliott, B. T. (2019). Short-Term Exercise Training Inconsistently Influences Basal Testosterone in Older Men: A Systematic Review and Meta-Analysis. Frontiers in physiology, 9, 1878. https://doi.org/10.3389/fphys.2018.01878 EXERCISE RECOMMENDATIONS FOR MEN AS TESTOSTERONE DECLINES • Follow CSEP Guidelines for older adults • Aerobic exercise to support weight loss if appropriate • Ideally higher (mod-vigorous) intensity for extended period (>30min) • Resistance training to prevent muscle decline and maintain strength THURSDAY CLASS • Journal Club Demo by Gina • Pick your paper and meet up with your group Journal club self-sign up closes tonight (Tuesday). Everyone will be assigned to a group tomorrow