Individual Approach to Hormone Replacement Therapy – A Computer Assisted Method of Assessment of the Minimal Useful Dose

Estrogen replacement therapy (ERT) was primarily used to treat vasomotor symptoms, it had been increasingly viewed as a way to prevent chronic diseases of aging, including coronary heart disease (CHD), cognitive impairment and osteoporosis [1-3]. Osteoporosis leads to bone fractures. Death rate due to osteoporosis is higher than the mortality rate attributed to breast and endometrial cancer combined. Estrogens are considered the gold standard in assessing the efficacy of various medications in osteoporosis treatment [1,2]. At least 40% of postmenopausal women in the United States were using ERT before the publication of the Women’s Health Initiative (WHI) report, which addressed the risks and benefits of ERT [1,4]. WHI trials addressed the most commonly used hormone formulations at the time in the United States -conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA). Findings from these trials have been extensively published during the past decades [5-7].


Short Communication
Estrogen replacement therapy (ERT) was primarily used to treat vasomotor symptoms, it had been increasingly viewed as a way to prevent chronic diseases of aging, including coronary heart disease (CHD), cognitive impairment and osteoporosis [1][2][3]. Osteoporosis leads to bone fractures. Death rate due to osteoporosis is higher than the mortality rate attributed to breast and endometrial cancer combined. Estrogens are considered the gold standard in assessing the efficacy of various medications in osteoporosis treatment [1,2].
At least 40% of postmenopausal women in the United States were using ERT before the publication of the Women's Health Initiative (WHI) report, which addressed the risks and benefits of ERT [1,4]. WHI trials addressed the most commonly used hormone formulations at the time in the United States --conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA). Findings from these trials have been extensively published during the past decades [5][6][7].
Manson et al. [1] conducted an extensive study involving 27,347 postmenopausal women aged 50 to 79 years from 1993 to 1998 at 40 US medical centers; 16,608 women with uterus present were randomized to oral CEE (0.625 mg/d) plus MPA (2.5 mg/d) (Prempro) or placebo, and 10,739 women with prior hysterectomy were randomized to oral CEE (0.625 mg/d) alone (Premarin) or placebo. CHD and invasive breast cancer served as primary outcomes. The study results were summarized as follows: For every 10,000 women taking CEE plus MPA per year, there were 6 more coronary events, 9 more strokes, 9 more pulmonary emboli, 9 more cases of breast cancer compared to the placebo group, and 6 fewer cases of colorectal cancer, 1 fewer case of endometrial cancer, 6 fewer hip fractures, and 1 fewer death compared to the placebo group [1].
In menopausal women aged 50-54 years with moderate or severe hot flashes, night sweats, administration of both the CEE and MPA and CEE alone caused substantial reductions in symptoms (64% and 28%, respectively, vs placebo at 1 year). ERT was also associated with statistically significant benefits for physical functioning and general health [1]. Almost half of women aged 60 to 65 years without HRT reported menopausal complaints and nearly two thirds experienced sexual dysfunction [8,9].
Most of the researchers emphasized the importance of developing individual minimal effective dose for each patient with the goal to treat her symptoms and decrease the risk of complications. Shufell et al. [10] studied the risk of breast cancer in HRT users and concluded that the lower breast cancer risk extends to lower doses of ERT prepation [10].

They included postmenopausal women from the Nurses' Health
Study . Authors concluded that vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer and was an effective treatment for genitourinary syndrome of menopause (GSM) [11]. GSM occurs in up to 45% of peri and postmenopausal women adversely impacting physical and sexual health. Vaginal estrogen therapy allows for the restoration of the vaginal epithelium with an increase in the number of superficial cells and normalization of acidic pH, which restores the normal flora and decreases vaginal dryness and dyspareunia [13]. The

North American Menopausal Society and the American College of
Obstetricians and Gynecologists (ACOG) recommend that low-dose vaginal estrogens be used to treat the symptoms [12,13].
We didn't use vaginal cream as a main form of ERT because of the difficulty to measure an appropriate amount of medication. We

Conclusion
We presented what appears to be the first attempt to use computer algorithm for selecting a minimum useful dose of ERT based on parameters (weight, age, symptoms, etc.) and treatment priorities of an individual patient. We hope that in the near future, patients would be able to input their personal data on a website and receive a minimal individualized effective dose. The website's recommendations will under no circumstances replace the patient's clinicians. The final decision on the type and dose of ERT will be of the patient's healthcare provider.