Abstract P039: Physiologic Transdermal Sex Steroid Hormone Replacement Therapy and Effects on Cardiovascular Biomarkers, Quality of Life, and Age- related Decline in Peri/Postmenopausal Women
Authors: Stephenson Kenna , Kurdowska Anna , Neuenschwander Pierre , Olusola Patti , Brown Sally , Kapur Sanjay , Zava David , Healy Patrick J , Stephenson John , Kinsey Robert 
Published: July 2021

Background:
Menopause annually affects 25 million women worldwide, and WHO estimates 1.2 billion women will be postmenopausal by 2030. Symptoms of vasomotor changes resulting in hot flashes and night sweats, dysphonic mood, and sleep disturbances affect quality of life in this aging population. Age- related conditions including cardiovascular disease, depression, osteoporosis, osteoarthritis, dementia, and frailty, are linked to menopause. Conventional oral HRT results in increased adverse effects and health outcomes as revealed in the WHI, yet animal studies and some epidemiologic data support benefits of HRT.

Hypothesis:
Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a favorable risk/benefit profile yet comparative effectiveness studies of this treatment model long term are lacking.

Methods:
Participants were recruited from the community at large. 300 women gave signed consent, and 75 met strict inclusion/exclusion criteria. Each subject was age and ethnicity matched to a control in the family medicine or women’s clinics. Treatment model subjects(n=75) received physiologic sex steroid transdermal therapy including: estrogen, progesterone and androgens, titrated to physiologic reference ranges. Treatment subjects were prohibited from use of lipid lowering or anti-inflammatory drugs. Control subjects (n=75) received usual care including conventional HRT and lipid lowering drugs. Subjects were evaluated at baseline and follow-up at 3 years for comparative effectiveness on biomarkers related to cardiovascular disease, health outcomes, and quality of life measures. Mixed modeling analysis tested for main effects and group by time interactions including relevant covariates.

Results:
Of the 9 measures, 4 revealed statistically significant interactions between group membership and time. Fasting Glucose, Co-morbidities, Medication use, and Pain displayed patterns of means indicating that the Treatment Model group either improved while the status quo group remained constant, or the Treatment Model group remained constant while the status quo worsened. Triglycerides improved in both groups. No significant group interactions occurred for BMI and blood pressure. Treatment model subjects did not have any adverse events or adverse changes in inflammatory, hemostatic or endometrial measurements, and improvements occurred for: Visual Analog Bodily Pain, Greene Climacteric Scale, Hamilton Anxiety/ Depression Scales.

Conclusion:
Transdermal physiological sex steroid hormone therapy was not associated with any adverse events or effects over 3 years, and lead to improved health outcomes and favorable changes on some biomarkers of cardiovascular disease, health outcomes, and quality of life indicators as compared to usual care in aging women.