Studying the Starvation Effect on Androgen Metabolism in 20 Healthy Young Women and Comparison to Women With PCOS.
Condition: PCOS Disease
MeSH terms: Starvation
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Androgen metabolism after starvation
Intervention type(s): Other
Intervention description(s): The 20 women will all undergo the same process of starvation for 48 hours. During this time three blood samples and three 24-hours urine samples will be collected. At baseline, the investigators will draw blood, perform a pregnancy test and collect the 24 hours urine as well as a spot urine.
Then the 48 hours starvation starts and two blood 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.
Intervention MeSH terms: Androgens
Intervention model: Single Group Assignment
Intervention model description: Clinical study with biological sampling in healthy young women being nutrionally restricted (using encoded data)
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: starvation; androgens; healthy women; PCOS