Nonhuman Primate Models of Menopause Workshop1

Abstract

The Nonhuman Primate Models of Menopause Workshop was held on the National Institutes of Health campus in January 2001. The purpose of this workshop, sponsored by the National Institute on Aging, was to review what is known about the female reproductive aging process in various species of monkeys (particularly rhesus, baboons, cynomolgus, and chimpanzees), including hormone profiles during the menopausal transition, occurrence of hot flashes, extent of age-related and menopause-associated changes in hormone levels on metabolism, bone loss, and impaired cardiovascular and cognitive function. Many aspects of the female reproductive aging process appear to be concordant between humans and these monkey species, but several important features may be species-specific. Those features that appear to parallel human menopause and aging include general similarity of hormone profiles across the menopausal transition, progression to cycle termination through irregular cycles, declining fertility with age, age-related gains in weight and percentage body fat content (with tendencies toward insulin resistance and glucose intolerance), increased low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol, declines in serum dehydroepiandrosterone, similarities in temperature-regulation systems, protective responses to estrogen replacement following ovariectomy in terms of bone metabolism, lipid profiles, and cognitive changes. Important differences include relatively short postmenopausal life span, timing in menopause-related changes in hormone secretion, and seasonal menstrual cycles. In addition, the question of whether ovariectomy in young adults is an appropriate model for the consequences of natural or surgical menopause in middle-aged and older adults is unresolved, and the numbers of older female animals available for research on menopause are very limited. The use of animal models is seen by workshop participants to be crucial for a mechanistic understanding of the human menopausal process and its connections to postmenopausal health problems; however, extensive in-depth and broad-based research is required to determine if nonhuman primates are appropriate models of human menopause.

Aging in Rhesus Monkeys: Relevance to Human Health Interventions

“…The circulating concentration of testosterone and its pulsatile release decline with age in male rhesus monkeys (37). Rhesus females experience the perimenopausal transition similar to women at similar stages of the life-span, but the age of initiation of endocrine changes varies in both species (38,39). As the perimenopausal transition progresses in women, gonadotropin levels increase.…”

Menopause occurs late in life in the captive chimpanzee (Pan troglodytes)

“…While the bonobo was menopausal, the two chimpanzees showed evidence of continued ovulation, albeit in an altered, perimenopause-like pattern. When findings of a workshop convened by the National Institute on Aging (NIA) were published more than two decades later, these two studies, comprising a total of 12 old chimpanzees, were found to be the only reports on chimpanzee menopause (Bellino and Wise 2003). The authors summarized the state of knowledge at that time by concluding that menstrual cycles continue until the end of natural life in this ape.…”

Age as a determinant of reproductive success among captive female rhesus macaques (Macaca mulatta)

“…Nevertheless, while rhesus monkeys experience similar reproductive changes as women, there is a significant difference in the timing of these events (Bellino & Wise 2002), which might, in part, stem from the seasonal breeding pattern of rhesus monkeys. Indeed, Shideler et al (2001) monitored rhesus monkeys for a complete year and found that menstrual cycling in older females frequently ceased during the nonbreeding season.…”