Abstract
During the transition to menopause, women experience a variety of physical and psychological symptoms that are directly or indirectly linked to changes in hormone secretion. Establishing animal models with intact ovaries is essential for understanding these interactions and finding new therapeutic targets. In this study, we assessed the endocrine profile, as well as the estrous cycle, in the 4-vinylcyclohexene diepoxide (VCD)-induced follicular depletion rat model in 10-day intervals over 1 month to accurately establish the best period for studies of the transition period. Twenty-eight-day-old female rats were injected daily with VCD or oil s.c. for 15 days and euthanized in the diestrus phase approximately 70, 80, 90 and 100 days after the onset of treatment. The percentage of rats showing irregular cycles and the plasma level of FSH increased only in the 100-day VCD group. Plasma anti-Müllerian hormone (AMH) and progesterone were lower in all VCD groups compared to control groups, while estradiol remained unchanged or higher. As in control groups, dihydrotestosterone (DHT) progressively decreased in the 70-90-day VCD groups; however, it was followed by a sharp increase only in the 100-day VCD group. No changes were found in plasma corticosterone, prolactin, thyroid hormones or luteinizing hormone. Based on the estrous cycle and endocrine profile, we conclude that 1) the time window from 70 to 100 days is suitable to study a perimenopause-like state in this model, and 2) regular cycles with low progesterone and AMH and normal FSH can be used as markers of the early/mid-transition period, whereas irregular cycles associated with higher FSH and DHT can be used as markers of the late transition period to estropause.
Highlights
Perimenopause is the transition period from the reproductive to the nonreproductive stage of life and includes the last reproductive years through the first twelve consecutive months without a menstrual period [1]
In a previous study from our group, we reported that [24, 32], the same percentage of irregular cycles was observed in vinylcyclohexene diepoxide (VCD) and oil-treated rats until nearly 85 days after the onset of treatment, showing that the irregularity of the estrous cycle until 85 after VCD treatment onset was not due to an effect of VCD, but rather to a random effect of our colony of rats
Because three rats from the 100-day group were in constant estrus, euthanasia was done at this stage of the estrous cycle in these rats
Summary
Perimenopause is the transition period from the reproductive to the nonreproductive stage of life and includes the last reproductive years through the first twelve consecutive months without a menstrual period [1]. This period corresponds to the final depletion of oocytes and can last up to 10 years, at time women may experience important changes in their hormone. Endocrinology of a perimenopausal rat model analysis, decision to publish, or preparation of the manuscript
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