The Progression From Dysmenorrhoea to Chronic Pelvic Pain

The Progression From Dysmenorrhoea to Chronic Pelvic Pain: Investigation of the Role of Chronic Inflammatory Pain Phenotype in Peripheral Blood as a Potential Biomarker.

This is a cross-sectional observational study.

For participants resident in Adelaide, South Australia.

The study consists of 3 visits to the Pain and Anaesthesia Research Clinic (PARC), within the Royal Adelaide Hospital (RAH).

A total of 56 participants will be recruited for this study.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Pelvic Pain; Dysmenorrhoea
• Intervention / Treatment: Drug: OCPs

Detailed Description

The study will involve a screening visit followed by two visits to PARC for blood sampling and questionnaires.

At the baseline visit, blood samples to assess biomarkers and confirm hormonal status will be taken.

From screening until the final study visit a total of approximately 120 mL in blood samples will be taken from each participant.

The study aims to further knowledge in the presence of severe pelvic pain in young women which is an area that has been under-researched with regard to it's impact on society.

The study proposes to enroll 7 groups of 8 healthy nulliparous women aged 18-35 with the following characteristics:

Mild or absent dysmenorrhoea (pain scale 0-3) and no other pelvic pain symptoms. (3 groups)

• Group 1, without contraceptive pill use
• Group 2A , contraceptive pill user and with a history of mild or absent dysmenorrhoea prior to pill use
• Group 2B, contraceptive pill user and with a history of severe dysmenorrhoea (pain scale 7-10) prior to pill use

Severe dysmenorrhoea (pain scale 7-10), but without chronic pelvic pain. (2 groups)

• Group 3, without contraceptive pill use
• Group 4, contraceptive pill user

Chronic pelvic pain and severe dysmenorrhoea (2 groups)

• Group 5, without contraceptive pill use
• Group 6,contraceptive pill user

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • PARC, Royal Adelaide Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Nulliparous women in good general health (can experience dysmenorrhoea (abscent, mild or severe), with or without pelvic pain and with or without contraceptive pill use)

Description

Inclusion Criteria:

• Age between 16 to 35 years old

Exclusion Criteria:

• Irregular menstrual cycles
• Use of any reproductive hormonal preparations (other than the combined oral contraceptive pill), thyroxine, insulin or corticosteroids
• Presence of an inflammatory process, or clinically significant infection in the 4 weeks
• Clinically significant renal, hepatic, cardiac, auto-immune disease
• Current use of immunosuppressant medication such as hydroxychloroquine, methotrexate or azathioprine
• Inability to read or comprehend the written information provided
• Current use of medications known to affect TLR responsiveness including amitriptyline or minocycline
• Current use of any analgesics, including non-steroidal anti-inflammatory medications and opioids for 5 drug half-lives prior to the day of testing
• Current or previous pregnancy
• Body Mass index less than 18 or more than 30

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Mild or absent dysmenorrhoea and no other pelvic pain symptoms without contraceptive pill use.
Group 2A; History of mild or absent dysmenorrhoea prior to pill use and no other pelvic pain symptoms with contraceptive pill use (Participants already using contraceptive pills).	Drug: OCPs; Participants in the contraceptive pill groups can use any one of the following contraceptive pills: Oestradiol valerate and dienogest, drospirenone and ethinyl estradiol , ethinyloestradiol and levonorgestrel, cyproterone and ethinyl estradiol, ethinylestradiol and norethisterone, Nomegestrol Acetate and Oestradiol and Ethinyl Estra
Group 2B; History of severe dysmenorrhoea prior to pill use and no other pelvic pain symptoms with contraceptive pill use (Participants already using contraceptive pills).	Drug: OCPs; Participants in the contraceptive pill groups can use any one of the following contraceptive pills: Oestradiol valerate and dienogest, drospirenone and ethinyl estradiol , ethinyloestradiol and levonorgestrel, cyproterone and ethinyl estradiol, ethinylestradiol and norethisterone, Nomegestrol Acetate and Oestradiol and Ethinyl Estra
Group 3; Severe dysmenorrhoea but without chronic pelvic pain and without contraceptive pill use.
Group 4; Severe dysmenorrhoea but without chronic pelvic pain and with contraceptive pill use (Participants already using contraceptive pills).	Drug: OCPs; Participants in the contraceptive pill groups can use any one of the following contraceptive pills: Oestradiol valerate and dienogest, drospirenone and ethinyl estradiol , ethinyloestradiol and levonorgestrel, cyproterone and ethinyl estradiol, ethinylestradiol and norethisterone, Nomegestrol Acetate and Oestradiol and Ethinyl Estra
Group 5; Chronic pelvic pain and severe dysmenorrhoea without contraceptive pill use
Group 6; Chronic pelvic pain and severe dysmenorrhoea with contraceptive pill use (Participants already using contraceptive pills).	Drug: OCPs; Participants in the contraceptive pill groups can use any one of the following contraceptive pills: Oestradiol valerate and dienogest, drospirenone and ethinyl estradiol , ethinyloestradiol and levonorgestrel, cyproterone and ethinyl estradiol, ethinylestradiol and norethisterone, Nomegestrol Acetate and Oestradiol and Ethinyl Estra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactivity of stimulated isolated peripheral blood immune cells	To determine if there are different inflammatory pain phenotypes between young women with either severe dysmenorrhoea alone, chronic pelvic pain from controls with mild or no dysmenorrhoea from the collected peripheral blood immune cells (assessed by cytokine output).	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of pelvic pain on everyday activities using the Pelvic Pain Questionnaire	Secondary efficacy end point	2 weeks
Levels of anxiety and depression using the DAS21	Secondary efficacy end point	2 weeks

Collaborators and Investigators

• Sponsor: University of Adelaide
• Investigators: Principal Investigator: Susan Evans, MBBS, PARC Research Clinic

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: December 6, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimated): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Biomarker; TLR2; TLR4; Inflammatory pain; TLR responsiveness; Peripheral blood responsiveness
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathologic Processes; Menstruation Disturbances; Chronic Pain; Pelvic Pain; Dysmenorrhea
• Other Study ID Numbers: PPAI-001

Plan for Individual participant data (IPD)

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