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Impact of Menopausal Hormone Formulations on Pituitary-Ovarian Regulatory Feedback

Kling JM1Dowling NM2Bimonte-Nelson HA3Gleason CE4Kantarci K5Manson JE6Taylor HS7Brinton EA8Lobo RA9Cedars ML10Pal L11Neal-Perry G12Naftolin F13Harman SM14Miller VM15.

Am J Physiol Regul Integr Comp Physiol. 2019 Oct 30. doi: 10.1152/ajpregu.00234.2019. [Epub ahead of print]



Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of post-menopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45± 2.49 years of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE, n=109), transdermal 17β-estradiol (t-E2, n=107), or placebo (n=146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum prior to (baseline) and 48 months after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE , t-E2, and placebo on these hormone levels at 48 months adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 months within treatment groups. As expected, at 48 months of treatment, hormone levels differed between women in the two active treatment groups compared to placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups as compared to placebo. Associations among testosterone, 17β-estradiol, FSH and LH differed between the o-CEE group compared to t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and inter-hormonal associations in recently menopausal women. These interactions provide the basis for future studies investing the impact of hormonal modulation of aging including cognitive decline in women.