A New Hormone Replacement Paradigm: Physiologic Restoration Study

Phase 4

• Conditions: Menopause Related Conditions; Perimenopausal Disorder; Menopause
• Interventions: Biological: Compounded topical estradiol and compounded topical progesterone in a carrier cream

• Registration Number: NCT04190927
• Lead Sponsor: Women's Hormone Network

Brief Summary

This is a three-year, prospective, observational study looking at the benefits of rhythmically dosed, bio-identical hormones compounded in a carrier cream in 100 symptomatic peri and postmenopausal women. This study will measure changes in cognition, mood, quality of life, endocrine health, bone mineral density, and reduction of the symptoms of menopause and any adverse effects. The objectives of this study are to show that rhythmic dosing of bio-identical hormones that mimic a menstrual cycle, are possible, and may be more beneficial and have fewer side effects than the current standard of care for treating the symptoms of menopause.

Detailed Description

"Bio-identical" hormones, which are compounded plant-based hormones synthesized into structurally similar to human estradiol and progesterone molecules, became popular in 2004 by celebrity, Suzanne Somers, who let women know there were natural alternatives to the drugs with hormone-like activity. Compounding hormones makes it easy to make dose adjustments in order to manage symptoms. Using this form of hormone delivery, it is possible to try and replicate a normal physiological reproductive pattern of replacement akin to thyroid replacement, etc. Current short-term studies with bio- identical transdermal estradiol and progesterone have not supported increased breast cancer or other issues such as venous thrombosis7. Even the WHI stated that the increase in breast cancer was due to stimulation of cancers already present.

This study of bio-identical physiologic restoration and dosing of estradiol, testosterone and cyclical transdermal progesterone attempts to replicate the reproductive hormone patterns and levels of a premenopausal woman. This dosing schedule has higher doses and levels than current standard estradiol and progesterone hormone therapy for post menopause women. Research shows that the estradiol peak of a menstrual cycle has an impact on cell signaling and receptor response. For example, TP53, the gene major tumor suppressor gene is under estrogen and progesterone control. At the peaks of estradiol and progesterone, TP53 is up regulated conferring cellular protection against mutations8-14.

Physiologic Restoration (PR) with bio-identical rhythmic dosing was originally developed by S.T. Wiley, who developed a template of hormone doses over time and was meant to be adjusted to the individual women depending on their symptoms and, absorption, metabolism, and response to the program. This study will utilize this concept with some improvements to the original proposed template (Sex, Lies, and Menopause, 2004). This regimen has been in national clinical practice since 2004 and has not been formally studied until now. There is unpublished observational data from Dr. Taguchi's high risk population of oncology patients (Santa Barbara Cottage Hospital IRB# 19-71ix) showing that PR is feasible and manages menopause symptoms well without seemingly more adverse effects and better sense of well being and excellent reversal or improvement of osteoporosis.

Study Timeline

• Study First Submitted: 2019-11-22
• Study First Submitted QC: 2019-12-05
• Study First Posted: 2019-12-09
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-30
• Last Update Posted: 2020-04-01
• Study Start: 2020-06-01
• Primary Completion: 2023-06-01
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

1. Symptomatic perimenopausal or menopausal women as determined by symptoms, history, or labs that confirm menopause status.
2. Any women interested in physiologic restoration for HRT replacement.
3. Women with a history of breast, endometrial or ovarian cancer who are seeking HRT regardless of their diagnosis and recommendations not to have HRT. They must understand the risk and give informed dissent.
4. Hysterectomy.

Exclusion Criteria

1. Women who are pregnant and or breastfeeding.
2. Women who may be allergic to the base used for compounding.
3. Previous recent (< 12 months) rhythmic dosing hormone protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Compounded topical estradiol and compounded topical progesterone in a carrier cream	All patients will be symptomatic peri or post menopausal and will all be started on the same protocol. The Dosing schedule of topical estradiol and topical progesterone will be modified for each subject in the first three months to address individual symptoms. The dosing will be relatively unique to each patient. Patients will remain on their dosing schedule for the remainder of the three year study and will be assessed during at the end of the study for changes in mood, symptoms of menopause, breast health, BMD and thickness of uterine lining .

Primary Outcome Measures

Name	Time	Method
Change in Symptoms of Menopause	36 months	Measure changes in hormone levels and blood chemistry, assess changes in mood and cognitive function, measure changes in brain structure
Change in Bone Mineral Density	36 months	Bone Mineral Density will be monitored for changes
Compliance of this HRT Regimen	36 months	Measure compliance of patients on this specific HRT regimen

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse effects	36 months	Measure incidence of cancer, embolism, coronary artery disease and stroke