Clinical trial NCT06686537: Convergent Mechanisms Underlying Reprometabolic Syndrome in Women
Official title: Convergent Mechanisms Underlying Reprometabolic Syndrome in Women and Sheep
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Infertility, Female
Obesity
Keywords: Obesity
Infertility
Hypothalamic-pituitary-ovarian axis
pituitary dysfunction
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Colorado Clinical & Translational Sciences Institute
First posted: 2024-11-13
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Dr. Nanette Santoro proposes to test the specific question that obesity results in abnormal estradiol response at the level of the pituitary and hypothalamus. This will be shown in diminished pituitary sensitivity to gonadorelin releasing hormone with a reduced estradiol induced luteinizing hormone surge in obese women.

Detailed description: This is an open-label, single site study in pre-menopausal women aged 18-40 years old with a history of regular menstrual cycles (25-35 days long) of normal BMI or high BMI. The objective of the study is to determine the effects of an estradiol patch on luteinizing hormone rise in both cohorts. The study consists of 2 periods: a screening period of up to 3 weeks and a Treatment Period of 7-10 days. During the treatment period participants will wear estradiol patches for up to 7 days and have on blood draw on day 3 of wearing the patches. Participants will also collect daily morning urine for all the days they wear the patches. Participants will use a reliable barrier method of birth control or abstain from intercourse for the duration of the study.

Eligibility criteria: Inclusion Criteria:

* Age 18-38
* Regular menstrual cycles every 25-35 days
* No use of reproductive hormones within the past 3 months
* No use of medications interacting with reproductive hormones
* Agreement to use reliable barrier contraception or to abstain from intercourse for the duration of the study
* Normal thyroid stimulating hormone, prolactin and lipid profiles
* No more than 4 hours of moderate to vigorous intensity exercise per week
* No history of chronic disease impacting reproductive hormones
* No contraindications to administration of estradiol
* No history of estrogen dependent cancer
* Negative pregnancy test

Exclusion Criteria:

* Has diabetes
* Is a smoker
* History of venous thromboembolism or known thrombophilia

Primary outcomes:
measure: Amount of Luteinizing hormone Surge
timeFrame: From enrollment to the end of treatment is 7 days.
Secondary outcomes:
measure: Time of Luteinizing Hormone Peak
timeFrame: From enrollment to 7 days
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Aurora
country: United States
facility: University of Colorado-School of Medicine
state: Colorado
Study officials:
affiliation: University of Colorado School of Medicine
name: Nanette Santoro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
citation: Rovner P, Keltz J, Allshouse A, Isaac B, Hickmon C, Lesh J, Chosich J, Santoro N. Induction of the LH Surge in Premenarchal Girls Confirms Early Maturation of the Hypothalamic-Pituitary-Ovarian Axis. Reprod Sci. 2018 Jan;25(1):33-38. doi: 10.1177/1933719117741377. Epub 2017 Nov 19.