PCOS Disease Clinical Trial
Official title:
Starvation Effect on Androgen Metabolism in Healthy Young Women.
In this study, the investigators wanted to investigate the energy homeostasis and the steroid
metabolism of 20 healthy, young and normal weight women aged between 16-35 years before and
after a 48 hours fasting period.
The following substrates and hormone concentrations representing the carbohydrate, fat and
protein metabolism will be measured from plasma or urine before and after fasting: glucose,
insulin, lactate, alpha-synucleine, free fatty acids, beta-hydroxybutyrate (ketone bodies),
carnitine (surrogate for acetyl-CoA) and alanine (amino acids). In addition, the
investigators will measure 67 steroid metabolites by GC/MS and Biokrates AbsolutIDQ Steroid
Assay in all collected urines and blood samples.
In the analysis of the data, the investigators will focus on correlations between biochemical
parameters of the energy metabolism and parameters of the steroid metabolism, specifically
the androgens. In addition, the steroid profiles obtained from healthy young women before and
after fasting will be compared to steroid profiles of PCOS women in search for specific
differences.
The first aim of this study is to investigate the energy homeostasis and the steroid
metabolism of healthy, young and normal weight women aged 16-35 years, before and after a 48
hours fasting period. Furthermore, second aim of this study is the comparison of their
steroid profiles with PCOS women in search for specific differences.
In fact it might be therefore hypothesized that the energy metabolism in PCOS women functions
like under (glucose) starvation conditions. In a pilot experiment performed in a healthy
young women of normal weight, the investigators observed that short term starvation over 48
hours changed her steroid profile from normal to PCOS-like with elevated testosterone with
elevated testosterone, DHT and androsterone/etiocholanolone ratio. It has been suggested that
during normal fasting and feeding metabolic signals such as AMP/NAD+ and acetyl-CoA translate
the energy state into specific metabolic programs. The investigators suggest that androgen
biosynthesis might be one of these programs. Therefore, becoming hyperandrogenic during short
term starvation might be normal, and the regulation between energy balance and androgen
biosynthesis might be visible in healthy subjects, thereby hinting pathways leading to PCOS
and better treatment options.
In this study the investigators will recruit 20 healthy, normal weight women aged 16-35 years
with regular cycle and without drug treatment, including hormonal contraception.
Characteristics of the participant and written informed consent with the study will be
collected. The study will start 14-21 days after the last menstrual period of the
participant. Twenty-four hours prior the first study visit the participant will collect a 24
hours urine sample and a spot urine.
On day one of the study, the participant will come early morning for the first visit to the
Inselspital Bern. The participant will be informed again and the exact study protocol will be
explained to make sure the participant is willing to fulfil the study requirements. The
investigators will draw blood, perform a pregnancy test and collect the 24 hours urine as
well as a spot urine. At this point the starvation period will start (=intake to a maximum of
500-800 kcal/d for 24 hours, depends on the weight of the participant). A dietary plan is
provided by Mrs. T. Zürcher, Pediatric Dietician, Childrens' Hosp. Inselspital Berne.
This regimen is selected on the basis that the human body switches into a state of "hunger"
and starts to burn fat instead of glucose after about 12 hours. During a 48 hours fasting
period the metabolism changes dramatically. During this state hormonal and chemical changes
will be investigated in blood and urine samples. During the starvation the participants have
to stick strictly to the dietary restriction regimen, which they will monitor themselves. If
the participants fails to do so, they will be excluded from continuation of the study and
cannot participate a second time. Fasting state and thus compliance are visible in the
measured lab data (e.g. ketone bodies).
Two blood samples and two 24 hours urine samples and spot urines will be collected after 24
and 48 hours in the morning. After the third visit the study is completed for the
participant. The blood samples and urine samples will be stored at -20°C until the day of
measurement. If agreed by the participant, data and samples will be used for future studies
in the same research field.
The collected samples of the participant (three blood and three 24-hours urine samples) will
be analysed for metabolic markers (glucose, potassium, insulin, lactate, free fatty acids,
ketone-bodies (beta-hydroxy-butyrate), carnitin, alanin) and for a multitude of steroids
(progesterons, androgens, estrogens, corticosterones, mineralocorticoids, glucocorticoids).
The measurements will be conducted according to GLP-standards. All laboratory parameters will
be analysed in the University Hospital of Berne (Inselspital) in the laboratories of the
Institute of Clinical Chemistry and Steroid Laboratory of Nephrology.
The obtained data will be entered in an existing RedCap database established for PCOS
research of the PI. Laboratory data will be statistically analysed and compared to previous
data obtained from a currently closing PCOS study being analysed.
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