Progesterone and Resting Energy Expenditure

Study Overview
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Brief Summary
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This study evaluates the effect of micronized progesterone substitution in the luteal phase on resting energy expenditure in women during menopausal transition.

Detailed Description
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The majority of women report an increase of body weight of about 0.5 kg/year during the menopausal transition. However, the weight gain has not been attributed to menopause itself but rather to, e.g., a decrease of the basal metabolic rate due to aging, less energy expenditure and a non-adapted caloric intake. One of the first signs of the menopausal transition is a change in the bleeding pattern due to a disruption of the hypothalamus-pituitary-ovary-axis. The number of cycles with an insufficient luteal phase and anovulatory cycles with an insufficient or even absent luteal phase increase as the menopausal transition proceeds. Thus, in perimenopausal women progesterone endogenous exposure decreases in quantity and duration. By substituting progesterone during the luteal phase, irregular cycle and bleeding patterns can be normalized. However, besides the beneficial effects of progesterone on the course of a menstrual cycle it displays some features that may be preventive for weight gain. In this study only women in their early menopausal transition with menstrual cycle irregularities are included. By substituting progesterone during luteal phase the investigator tries to normalize their menstrual cycle pattern. The hypothesis is, that progesterone might not only normalize the menstrual cycle pattern of women in their early menopausal transition but due to its metabolic activities, progesterone may also increase the resting energy expenditure and thus may prevent weight gain during the menopausal transition. Furthermore the effect of progesterone substitution on the expression of miRNAs which are included in glucose- and lipid-metabolism such as miR-370 and miR-29 will be investigated.

Official Title
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Impact of Progesterone Substitution in Luteal Phase on Resting Energy Expenditure in Women During Menopausal Transition.

Conditions
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Menopause, Progesterone, Weight Gain

Intervention / Treatment
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* Drug: Utrogestan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women during early menopausal transition (MT) with indication for luteal phase progesterone substitution (definition of early MT: change of cycle length (shorter or longer menstrual cycle) of at least ≥ 7 days from normal and/or phases of amenorrhea of up to < 60 days during the preceding 12 months) Body Mass Index (BMI) 18.5 - 24.9 kg/m2 Informed Consent as documented by signature Exclusion Criteria: Pregnancy or Lactation Systemic hormone therapy or hormonal contraception (estradiol, progestogen, androgen) during the study and within 12 weeks prior to study entry Phytotherapeutics for menstrual cycle regulation during the study and within 12 weeks prior to study entry Active psychiatric disease Use of psychotropic drugs during the study and within 12 weeks prior to study entry Nicotin abuse > 10 cigarettes/day Alcohol abuse Use of appetite suppressants Diabetes mellitus Untreated Hypo- and hyperthyroidism Hypersensitivity to progesterone Hypersensitivity to sunflower oil, soy lecithin and other ingredients of Utrogestan® such as gelatine, glycerol, E171 (titanium dioxide) Contraindication of progesterone medication according to swissmedicinfo.ch (suspected or diagnosed neoplasia of the breast or other sexual organ; benign or malignant liver Tumors (also in medical history); acute or chronic liver disease (Rotor- or Dubin-Johnson-Syndrome); cholestatic jaundice; porphyria; arterial or venous thromboembolic Events and cerebral bleedings; abnormal genital bleeding of unknown cause) Use of barbiturates, antiepileptic drugs, tuberculostatic drugs, antiretroviral drugs, antimycotic drugs, antibiotic drugs, Hypericum perforatum and Spironolactone Known or suspected non-compliance, drug or alcohol abuse etc. Illiteracy Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Utrogestan<br>300mg Utrogestan (1 tablet 100mg + 1 tablet 200mg)by mouth,every day in the second and third menstrual cycle daily from cycle day 15 to 26. | Drug: Utrogestan<br>* 300mg Utrogestan (1 tablet 100mg + 1 tablet 200mg) in the second and third menstrual cycle daily from cycle day 15 to 26.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in resting energy expenditure | Change in resting energy expenditure (kcal/day) from cycle 1 due to substitution of Utrogestan in luteal phase | cycle 1 (day 20) to cycle 3 (day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in miRNA expression | Change in miRNA expression (miR-370, miR-29b) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in energy intake | Change in energy intake (kcal/day) | cycle 1 (day 17-19) and cycle 3 (day 17-19), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in body core temperature | Change in body core temperature (°C) | cycle 1-3 during luteal phase, (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in serum hormone profile FSH | Change in serum hormone profile: FSH (U/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in serum hormone profile LH | Change in serum hormone profile: LH (U/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in serum hormone profile estradiol | Change in serum hormone profile: estradiol (pmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20) | 
| Mean change in serum hormone profile progesterone | Change in serum hormone profile: progesterone (nmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in fasting glucose | Change in fasting glucose (mmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in fasting Insulin | Change in fasting Insulin (mU/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in blood lipid serum level: cholesterol | Change in cholesterol (mmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in blood lipid serum level: LDL | Change in LDL (mmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in blood lipid serum level: HDL | Change in HDL (mmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 
| Mean change in blood lipid serum level: triglycerides | Change in triglycerides (mmol/l) | cycle 1 (day 5; day 20) and cycle 3 (day 5; day 20), (cycle 1 has individual length, <60 days, cycle 2&3 are 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resting energy expenditure