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1007481.EMAS 2015 Abstracts.Pdf AN INTERNATIONAL JOURNAL OF MIDLIFE HEALTH AND BEYOND Volume 81 , Issue 1 ( 2015 ) 10th EMAS Congress 2015 Abstracts Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St. Louis Maturitas 81 (2015) 101–104 Contents lists available at ScienceDirect Maturitas journal homepage: www.elsevier.com/locate/maturitas Abstracts of plenary sessions Menopause, cognition and dementia PL2 PL1 Hormone therapy: Where are we now? Neurological consequences of premature Pauline Maki ∗ ovarian failure University of Illinois at Chicago, Psychiatry and Walter Rocca ∗ Psychology, Chicago, United States Mayo Clinic, Consultant, Rochester, United States Hormone therapy (HT) is the gold standard treatment for vaso- motor symptoms but is not approved for the treatment of cognitive In this invited lecture, I will discuss current knowledge and symptoms or the prevention of dementia. To date the only ran- the remaining unanswered questions concerning the neurolog- domized clinical trial to examine the effect of HT on dementia ical consequences of premature ovarian failure (POF). I will risk is the Women’s Health Initiative Memory Study (WHIMS), provide a narrative and conceptual review of the literature rather which indicated a doubling of the risk of dementia in women 65 than a systematic review. Most of what we know about POF years of age and older who were randomized to receive combined comes from studies of women who underwent bilateral oophorec- HT (conjugated equine estrogen (CEE) plus medroxyprogesterone tomy (induced versus spontaneous POF; Shuster et al., 2010). acetate) compared to women randomized to receive placebo. In Women who undergo bilateral oophorectomy before the onset a second arm of WHIMS, hysterectomized women 65 years of of menopause experience a sudden and complete loss of estro- age and older who were randomized to receive CEE showed a gen and other ovarian hormones at an age when such hormones non-significant increased risk of dementia compared to those are normally present. This group of women offers a unique set- randomized to receive placebo. Three observational studies have ting to study the effects of ovarian hormones on brain aging. Most examined whether the effect of HT on dementia risk depends on of the studies have focused on the effects of oophorectomy on the timing of initiation of HT. Each of those three studies indicates the risk of stroke, parkinsonism, and dementia. As an example, I that timing of initiation is a significant modifier of the association will focus on dementia. We first reported evidence of an associ- between use of HT and risk of AD and that the greatest reduc- ation between bilateral oophorectomy and cognitive impairment tion in AD is evident when HT is used early or by women younger or dementia from the Mayo Clinic Cohort Study of Oophorectomy than 60 years of age. Some evidence suggests that use of combined and Aging in 2007 (Rocca et al., 2007). The risk increased with HT at midlife for five years might be optimal, and that benefits younger age at oophorectomy, did not vary by indication for the might be reduced with longer use. Unfortunately, it is not feasi- oophorectomy, and was attenuated by estrogen treatment after the ble to conduct a randomized trial of HT for primary prevention surgery. The findings from the Mayo Clinic study were replicated of AD in women who initiate HT at midlife. Longitudinal studies three years later by a Danish nationwide study (Phung et al., 2010; of objective cognitive performance indicate that memory declines Rocca et al., 2012), four years later by a Chinese study (Zhou et al., from the premenopausal stage to the early and late perimenopause 2011), and most recently by a second US study (Bove et al., 2014; and might resolve during the postmenopausal stage. Neuroimag- Rocca et al., 2014). In the recent US study, women who underwent ing evidence indicates that women who initiate HT before the final early surgical menopause had faster cognitive decline, developed menstrual period show enhanced memory and function of the hip- more neuritic plaques, and had worse global pathology scores. That pocampus. Additional studies are needed to evaluate whether the study also showed a beneficial effect of estrogen treatment after the optimal window of opportunity for use of HT might be during the oophorectomy (Bove et al., 2014). Many questions remain unan- perimenopausal stage. swered, and more research on the consequences of POF is needed. http://dx.doi.org/10.1016/j.maturitas.2015.02.069 http://dx.doi.org/10.1016/j.maturitas.2015.02.068 0378-5122/$ – see front matter 102 Abstracts / Maturitas 81 (2015) 101–104 PL3 tics of oogonial stem cells. They are purported to have the ability to form new oocytes and follicles after reintroduction into the ovary, The critical window hypothesis: implications of or in reaggregation models, and one group has reported healthy cognitive outcomes from the ELITE clinical trial offspring. We have isolated cells from both human and bovine Victor W. Henderson 1,∗, Howard N. Hodis 2, Jan A. ovary, using a DDX4 antibody/FACS approach, that will proliferate St. John 2, Carol A. Mccleary 2, Frank Z. Stanczyk 2, in long-term culture, and express a range of pluripotency and germ Donna Shoupe 2, Naoko Kono 2, Laurie Dustin 2, cell markers including LIN28, OCT-4, IFITM3, STELLA, BLIMP1 and Hooman Allayee 2, Wendy J. Mack 2, ELITE CKIT. Stable labelling with GFP can also be achieved after lentivirus Research Group transduction. Importantly, there are no data relating to the poten- tial physiological role of these cells within the ovary. These cells 1 Stanford University, Stanford, CA, United States do however offer opportunities to study germ cell biology in a 2 University of Southern California, Los Angeles, CA, novel in vitro model, and if their potential for follicle formation United States and restoration of fertility can be demonstrated, they would offer wide-ranging opportunities, both biological and clinical. Introduction: It is hypothesized that menopausal hormone therapy used by women close to the time of menopause enhances memory, whereas no cognitive benefit—or even cognitive http://dx.doi.org/10.1016/j.maturitas.2015.02.071 harm—results from use by older women. Objectives: To test the timing, or critical window, hypothesis of Menopause and its prediction cognitive benefit. PL5 Aims: We predicted that change in verbal episodic mem- ory would be better for younger postmenopausal women near Menopause and its prediction menopause, randomised to oestradiol compared to placebo, but not ∗ for older postmenopausal women. Bart C.J.M. Fauser Methods: The Early versus Late Intervention Trial of Estra- University Medical Center Utrecht, Reproductive diol (ELITE) is a 2-by-2, randomised, double-blinded, placebo- Medicine & Gynecology, Utrecht, Netherlands controlled trial. The active intervention is oral oestradiol 1 mg/d, ±cyclic micronised progesterone vaginal gel. Women were ≤6y Bart CJM Fauser, Professor of Reproductive Medicine, Chair (Early group) or 10+ y (Late group) from menopause. The primary Department of Reproductive Medicine & Gynaecology, University cognitive outcome used change in a verbal memory composite Medical Center Utrecht, Utrecht, The Netherlands score assessed at baseline, 2.5 y and 5 y, compared between treat- Menopause represents the endpoint of exhaustion of the ovarian ment groups. Other composite outcomes were derived from scores follicle pool. Associated climacteric complaints are largely asso- for executive functions and global cognition. ciated with the coinciding estrogen deprivation. Next to short Results: 567 women who underwent cognitive assessment at term implications, increasing evidence suggests that the age of baseline and on at least one other occasion were included in menopause also affects general health, such as osteoporosis, breast modified intention-to-treat analyses (mean treatment duration cancer risk, cognition, cardiovascular risk and stroke. Hence, age of 57 mo). Treatment effect sizes were similar in Early and Late menopause and perimenopause management seems key factors in postmenopause groups for each of the three composite neuropsy- relation to healthy female aging since many girls born today are chological scores. In analyses that combined women in Early and expected to reach one hundred years of age. Consequently, half of Late groups, mean differences between oestradiol and placebo their lives will be after menopause. treatment groups were not significant. Age of menopause is also closely linked to preceding sterility and Conclusions: ELITE clinical trial results fail to confirm a criti- decreased natural fertility. On average women reach menopause at cal window during which oestradiol differentially affects cognitive the age of 50, and natural fertility is diminishing 20 years earlier. In outcomes. Findings suggest that postmenopausal women of any current Westerns societies, many women start thinking about hav- age should not use oestradiol to enhance verbal memory, execu- ing children when they are beyond 30 years of age. Due to the wide tive functions or global cognition. Women considering menopausal individual variability of age of menopause (normal range between hormone therapy need not be concerned that oestradiol adversely 40 and 60 years), preceding decreased fertility may also vary. Much affects cognitive skills over a 5-year period of use. (National Insti- research in recent years has convincingly demonstrated that anti- tutes of Health R01AG024154) Mullerian hormone
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