Prolactin Release Through Breast Stimulation in Non-lactating Women - Who Does Respond?

Prolactin is a multifunctional hormone which acts in different cell types rather than just modulating reproduction and lactation. One additional point is its action on glucose metabolism which is described especially in rodents. Prolactin affects proliferation, survival and insulin production of pancreatic beta cells in animal models. But also in human studies prolactin is linked to insulin action. Low systemic levels of prolactin are associated with increased prevalence of diabetes and while higher levels are associated with higher insulin sensitivity.

Acute metabolic effects of prolactin in young, healthy and non-lactating women should be accessed. Therefore, the induction of a transient increase of circulating prolactin levels is necessary to study the acute effects of this hormone on metabolic processes. This can most likely be achieved in non-pregnant and non-lactating women without pharmacological intervention.

As the main stimulus of prolactin release from the pituitary gland is the mechanical stimulation of the breast / nipple, like a suckling baby, stimulation by a breast pump might trigger prolactin release.

Due to other studies in this field, only a minority of women respond to breast stimulation with an increase in prolactin levels. Therefore, this pilot study will assess if an electric milk pump can stimulate prolactin release in non-lactating women. The second aim of the study is to identify factors which determine response and non-response to breast stimulation.

Prolactin will be measured in blood serum. The primary objective of this study is to identify women in whom a 30-minute breast stimulation causes a marked prolactin release. Response is defined as an increase at least twice the baseline value.

Second outcomes are the quantification and duration of prolactin increase as well as to detect differences in responders and non-responders. Therefore, demographic data as well as anthropometric data will also be assessed. A 10-minute electrocardiography and non-invasive measurement of resting energy expenditure by indirect calorimetry will also be performed. History of menstrual cycle, intake of contraceptive, parity and lactation experience will be recorded. Physical activity level and feeling of hunger will be assessed by questionnaires.

Feeling of hunger, resting energy expenditure, blood pressure, heart rate and body temperature will be assessed repeatedly to register differences before and after stimulation. Blood and urine samples will be assessed for safety.

Study Overview

• Status: Recruiting
• Conditions: Prolactin; Breast Stimulation
• Intervention / Treatment: Other: Breast stimulation

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louise Fritsche, Dr.rer.nat.; Phone Number: +4970712780687; Email: louise.fritsche@med.uni-tuebingen.de
• Study Contact Backup: Name: Dorina S. Löffler, M. Sc.; Phone Number: +4970712780687; Email: dorina.loffler@med.uni-tuebingen.de

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • Recruiting
    • University Hospital Tuebingen, Otfried-Mueller Str. 10
    • Contact: Louise Fritsche, Dr.; Phone Number: +49 (0)7071 29 80687; Email: louise.fritsche@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women, aged between 18 and 45 years
• premenopausal (women, who had menses at any time in the preceding 24 consecutive months)
• BMI < 25 kg/m²
• Ability to understand and voluntarily sign an informed consent document prior to any study related procedures

Exclusion Criteria:

• Type 1 or Type 2 diabetes
• Intake of medication which may affect prolactin levels (e.g. Metoclopramide, Methyldopa, opiates, cimetidine), except birth control pill/hormonal contraception known hyperprolactinemia or hyperthyroidism
• any other serious illness that might impact the results as judged by the investigator (e.g. malignant disease, coronary heart disease)
• Pregnant / breastfeeding women (weaning at least 6 month ago)
• plastic breast surgery (with detachment of milk ducts)
• allergy to BPA-free plastic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Breast stimulation; A 30-minute stimulation with moderate intensity by an electric milk pump (Elvie Pump) will be performed.	Other: Breast stimulation; Breast stimulation by the Elvie Pump to trigger prolactin release.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolactin release - yes/no	The primary objective of this study is to identify women in whom breast stimulation causes a marked prolactin release. Response is defined as an increase at least twice the baseline blood value.	Sample collection will be from 0 to 90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolactin levels	Quantification, duration and trajectory of prolactin increase will be assessed by measuring prolactin levels in blood	Sample collection will be from 0 to 90 minutes
Differences in subjects age	Differences between responders and non-responders will be assessed: differences in age by recording birth date	1 minute
Differences in subjects BMI	Differences between responders and non-responders will be assessed: differences in Body Mass Index by measuring height and weight of subjects and calculate the BMI	4 minutes
Differences in subjects body fat content	Differences between responders and non-responders will be assessed: differences in body fat content by bioelectrical impedance analysis	3 minutes
Differences in subjects menstrual cycle phase	Differences between responders and non-responders will be assessed: differences in phase of menstrual cycle by recording the menstrual history	2 minutes
Differences in subjects intake of hormonal contraception	Differences between responders and non-responders will be assessed: differences in intake of hormonal contraception recording intake of medication	2 minutes
Differences in subjects parity	Differences between responders and non-responders will be assessed: differences in parity by recording family history	2 minutes
Differences in subjects history of lactation	Differences between responders and non-responders will be assessed: differences in history of lactation experience by recording history of lactation	2 minutes
Differences in subjects heart rate variability parameters: time domain (beats per minute)	Differences between responders and non-responders and within subjects will be assessed: differences in the time domain by two 10-minute 3 lead ECG measurements before and after stimulation	10 minutes
Differences in subjects heart rate variability parameters: Root Mean Square of successive RR interval differences (RMSSD)	Differences between responders and non-responders and within subjects will be assessed: differences in RMSSD by two 10-minute 3 lead ECG measurements before and after stimulation	10 minutes
Differences in subjects heart rate variability parameters: Standard deviation of RR-intervals (SDNN)	Differences between responders and non-responders and within subjects will be assessed: differences SDNN by two 10-minute 3 lead ECG measurements before and after stimulation	10 minutes
Differences in subjects heart rate variability parameters: frequency domain parameters	Differences between responders and non-responders and within subjects will be assessed: differences in low (LF) and high (HF) frequency power by two 10-minute 3 lead ECG measurements before and after stimulation	10 minutes
Differences in subjects heart rate variability parameters: Low to high frequency power ratio	Differences between responders and non-responders and within subjects will be assessed: differences in LF/HF - Ratio by two 10-minute 3 lead ECG measurements before and after stimulation	20 minutes
Differences in subjects physical activity level	Differences between responders and non-responders will be assessed: differences physical activity level by questionnaire including the baecke index	10 minutes
Differences in subjects stress reaction	Differences between responders and non-responders will be assessed: differences in stress, measured by cortisol levels in blood	Sample collection will be from 0 to 90 minutes
Changes in feelings of hunger through stimulation	Register change of feeling of hunger before and after stimulation by 15 questions on a five-point Likert scale survey about food cravings (FCQ-S)	10 minutes
Changes in resting energy expenditure through stimulation	Register change of resting energy expenditure before and after stimulation by indirect calorimetry	30 minutes (each 15 minutes)
Changes in blood pressure through stimulation	Register changes in blood pressure before and after stimulation using an automatic instrument with a digital readout	4 minutes
Changes in heart rate through stimulation	Register changes in heart rate before and after stimulation using an automatic instrument with a digital readout	4 minutes
Changes in body temperature through stimulation	Register changes of body temperature before and after stimulation by an ear thermometer	1 minute
Changes of Hypothalamic-Pituitary-Adrenal axis activity	Changes in Corticotropin levels are assessed by measurement in blood	90 minutes
Changes of Hypothalamic-Pituitary-Somatotropic axis activity	Changes in Somatotropin and insulin-like growth factor 1 levels are assessed by measurement in blood	90 minutes
Changes of Hypothalamic-Pituitary-Prolactin axis activity	Changes in Prolactin levels are assessed by measurement in blood	90 minutes
Changes of Hypothalamic-Pituitary-Thyroid axis activity	Changes in levels of Thyroid-stimulating hormone, Triiodthyronine and Thyroxine are assessed by measurement in blood	90 minutes
Changes of Hypothalamic-Pituitary-Gonadal axis activity	Changes in levels of Follicle stimulating hormone, Luteinizing hormone, estradiol and progesterone are assessed by measurement in blood	90 minutes

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PRL Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

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