Progesterone and Resting Energy Expenditure (P4&REE)

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

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

Study Overview

• Status: Terminated
• Conditions: Menopause; Weight Gain; Progesterone
• Intervention / Treatment: Drug: Utrogestan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Dep. of Obstetrics and Gynecology, Bern University Hospital, Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Utrogestan; 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; 300mg Utrogestan (1 tablet 100mg + 1 tablet 200mg) in the second and third menstrual cycle daily from cycle day 15 to 26.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Petra Stute, Prof, University Hospital Berne

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Resting energy expenditure
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 2018-01240

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No