Effect of Modifications of Nutritional Intake Upon Reproductive Hormones in Normal Women

Study Overview
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Brief Summary
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Undernutrition has a known and well recognized negative impact on reproductive hormones, and ultimately fertility. In contrast, much less is known regarding the potential effects of overnutrition on the same hormones. Epidemiological data suggest that overnutrition might have a deleterious impact as well on the fertile potential of affected women, but very little is known about the mechanisms implicated. Such knowledge may be of importance, given the increasing prevalence of overweight and obesity worldwide.

Detailed Description
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In the present study, the investigators will perform a very detailed study of the minute to minute regulation of hormones of the neuroendocrine reproductive axis in normal young female volunteers. These studies will initially be performed at base line during isocaloric diet, where the stimulation of LH secretion by exogenous insulin will be tested during hyperinsulinemic eugylcemic clamp studies. The same studies will then be repeated after a period of one month of controlled hypercaloric diet, where volunteers will receive an excess of approximately 30% KCal compared to their calculated daily energy expenditure. it is anticipated that such hypercaloric nutrition will induce a significant decrease in normal insulin sensitivity of these volunteers. Thus, the effect of changing whole body insulin sensitivity on the fine regulation of neuroendocrine reproductive hormones will be evaluated.

Official Title
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Effect of Metabolic Variations Upon the Activity of the Neuroendocrine Reproductive Axis in Normal Female Volunteers

Conditions
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Female Reproductive System Disorder

Intervention / Treatment
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* Other: Clamp
* Other: Hypercaloric diet
* Other: Basal
* Other: Isocaloric diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normally cycling young (between 18 and 30 yo) female, with a BMI between 20 and 25 kg/m2. - Exclusion Criteria: Personal history of endocrine dysfunction (any kind) Hormonal contraception Pregnancy Food allergy (any kind) Intense physical activity (>4 hrs/week) Smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypercaloric diet and basal<br>Volunteers fed a hypercaloric diet for one month will be submitted to a fasting period of ten hours duration | Other: Hypercaloric diet<br>* Hypercaloric diet will be conducted during one month, and designed to provide 30% excess in calories compared to daily requirements. It will consist in a high fat, high carbohydrates diet.<br>* Other names: Overfeeding;Other: Basal<br>* Keeping the volunteers in the fasting state overnight and for the entire duration of the experiment (10 hours)<br>* Other names: Fasting;|
| Experimental: Hypercaloric diet and clamp<br>Volunteers fed a hypercaloric diet for one month will be submitted to a hyperinsulinemic and euglycemic clamp of ten hours duration | Other: Clamp<br>* Volunteers will be submitted to hyperinsulinemic, euglycemic clamp studies of 10 hours duration.<br>* Other names: Hyperinsulinemic and euglycemic clamp study;Other: Hypercaloric diet<br>* Hypercaloric diet will be conducted during one month, and designed to provide 30% excess in calories compared to daily requirements. It will consist in a high fat, high carbohydrates diet.<br>* Other names: Overfeeding;|
| Active Comparator: Isocaloric diet and basal<br>Volunteers fed a isocaloric diet for one month will be submitted to a fasting period of ten hours duration | Other: Basal<br>* Keeping the volunteers in the fasting state overnight and for the entire duration of the experiment (10 hours)<br>* Other names: Fasting;Other: Isocaloric diet<br>* Isocaloric diet will conducted for one month, and designed to provide the calculated daily energy needs<br>* Other names: Controlled diet;|
| Experimental: Isocaloric diet and clamp<br>Volunteers fed a isocaloric diet for one month will be submitted to a hyperinsulinemic and euglycemic clamp of ten hours duration | Other: Clamp<br>* Volunteers will be submitted to hyperinsulinemic, euglycemic clamp studies of 10 hours duration.<br>* Other names: Hyperinsulinemic and euglycemic clamp study;Other: Isocaloric diet<br>* Isocaloric diet will conducted for one month, and designed to provide the calculated daily energy needs<br>* Other names: Controlled diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Luteinizing hormone secretion | The pulsatility of LH will be assessed by measuring LH levels in blood sample obtained every ten minutes over the entire study period (12 hours). | Every ten minutes for 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity will be defined as the rate of glucose infusion required to maintain euglycemia during the hyperinsulinemic clamp | 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LH pulsatility, Insulin sensitivity, Metabolism, hypercaloric feeding