Reprometabolic Syndrome Mediates Subfertility in Obesity

What Was Tested

This registered not phased trial tested Gonadorelin and Insulin (regular human).

This study will be the first comprehensive investigation to tie together the patterns of hyperinsulinemia, hyperlipidemia and inflammation, characteristic of obesity and obesity-caused relative hypogonadotropic hypogonadotropism and its potential adverse reproductive outcomes.

The investigators findings will be used to inform a subsequent clinical intervention to optimize reproductive outcomes for obese women and their offspring.

It had two arms (groups): Aim 1-Administration of FFA in an acute model (active comparator) and Aim 2-Hyperinsulinemic Euglycemic Clamp after a chronic administration of a diet (experimental).

Reproduction of the reproductive phenotype of obesity in Normal Weight Women (NWW) by: 1\) infusing insulin and free fatty acids (FFAs) in short term experiments and measuring gonadotropin pulsatility and pituitary GnRH response Assessment of the gluco-regulatory and anti-lipolytic actions of insulin with a 2-stage, Hyperinsulinemic, Euglycemic Clamp (HEC) to evaluate both suppression of lipolysis and hepatic glucose production.

Assessment of the gluco-regulatory and anti-lipolytic actions of insulin with a 2-stage, Hyperinsulinemic, Euglycemic Clamp (HEC) to evaluate both suppression of lipolysis and hepatic glucose production. Inducing a chronic model of the reprometabolic syndrome by administering a eucaloric diet that is relatively high in pro-inflammatory omega-6 fatty acids and low in anti-inflammatory omega-3 fatty acids (high fat diet; HFD) for one month while monitoring gonadotropin pulsatility and daily urinary reproductive hormone excretion.

The registry classes the interventions as drug and procedure.

More on the Plan

Before any of the well-known adverse effects in pregnancy2,3, obesity causes a relatively hypogonadotropic hypogonadal phenotype.

The researchers have named this phenotype the reprometabolic syndrome.

The researchers propose to examine the interrelationships among obesity, reproductive dysfunction and metabolic dysfunction in a mechanistic fashion.

Who Took Part

84 actual participants took part.

It was open to women only aged from 18 years up to 38 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Body Mass Index (BMI) at least 18 but less than 25 kg/m2. No history of chronic disease affecting hormone production, metabolism, or clearance. No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin). No use of reproductive hormones within 3 months of enrollment. Normal prolactin and thyroid stimulating hormone levels at screening.

The full record lists 9 inclusion and 5 exclusion criteria; among the exclusions: pregnant women or women planning to become pregnant will be excluded.

How the Study Was Run

It was run as a non-randomized, parallel-group and open-label study.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Everyone knew when Gonadorelin was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2016-06 with completion listed for 2023-12-11.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Researchers chose this as the main measure: Change in LH Pulse Amplitude Before and After Acute or Chronic FFA Administration (time frame: First 4 hours of the frequent blood sampling study before and after FFA administration). Change in Steady State Amount of Glucose Metabolized at the Set Insulin Infusion Rate Under Euglycemic Conditions (time frame: 30 minutes).

It also tracked 7 secondary outcomes, for example Change in GnRH Response Before and After Acute or Chronic FFA Administration, Change in Mean FSH Parameter Before and After Acute or Chronic FFA Administration, Changes in Gonadotropin Pulse Frequency, Urinary Hormone Profiles Before, During and After High Fat Diet Administration, Glucose Measurements Before and After FFA Administration and Comparison of RBC Lipids Before and After the FFA Administration.

What This Means in Plain Language

Put simply, this is a not phased, non-randomized trial of Gonadorelin and Insulin (regular human) in 84 people.

Its status is active not recruiting; results are posted on the registry, and this page does not restate them.

More context: the Gonadorelin compound page and the Insulin (regular human) compound page, all human trials.