To Establish Whether Individuals With Premenstrual Dysphoric Disorder (PMDD) Demonstrate a Different Luteal-phase Sex Hormone Profile and Ratio Compared With Asymptomatic Controls.

Premenstrual dysphoric disorder (PMDD) is a severe cyclical disorder characterised by affective, cognitive and physical symptoms occurring during the luteal phase of the menstrual cycle and resolving shortly after the onset of menstruation. Although circulating ovarian hormone concentrations are generally considered to be within physiological reference ranges, increasing evidence suggests that altered sensitivity to normal hormonal fluctuations, rather than absolute hormone concentrations alone, may contribute to symptom development.

The progesterone-to-oestradiol ratio has been proposed as a potential biological marker of luteal hormonal balance; however, this has not been systematically evaluated in individuals with PMDD compared with asymptomatic controls.

This observational case-control study will compare serum progesterone concentrations, serum oestradiol concentrations, and the progesterone-to-oestradiol ratio during the mid-luteal phase between participants with PMDD and healthy controls. Hormone measurements will be obtained following confirmation of ovulation using a urinary luteinising hormone (LH) surge, with blood sampling performed approximately seven days after the LH surge to standardise assessment within the mid-luteal phase.

The findings will provide preliminary evidence regarding whether alterations in the progesterone-to-oestradiol ratio are associated with PMDD and may inform future mechanistic studies investigating the endocrine basis of the disorder.

Inclusion criteria

• Aged 18-45 years old (adults but less than the typical perimenopausal age so there is not added bias/variable)
• Regular menstrual cycles (21-35 days for the last 3 months)
• Willing and able to complete a questionnaire (no new clinical diagnosis given)
• Use home urine LH test strips to detect ovulation
• Attend a single in person on site in Lancaster mid luteal blood test sample appointment (approx 7 days post LH surge)
• Provide written informed consent
• Have sufficient English language skills to understand the patient information
• Be either in Group 1 or group 2 Group 1 (PMDD group ie case group) - self reported prior diagnosis of PMDD made by a healthcare professional (GP, psychiatrist, gynaecologist) Group 2 (Control group ie comparison group) - no prior diagnosis of PMDD made by a healthcare professional and no history of clinically significant premenstrual mood symptoms on screening

Exclusion criteria

• Current use or use in the last 3 months of hormonal contraception such as the combined oral contraceptive pill, the progestogen only pill, the implant, the injection, hormonal coil (Mirena, Kyleena) or patch/ring.
• Current use or use in the last 3 months of any hormone replacement therapy (e.g. combined oestrogen and progesterone, oestrogen and Mirena coil combination, oestrogen alone if had a hysterectomy, or progesterone alone) or GnRH analogues use
• On a selective serotonin reuptake inhibitor (SSRI) with a recent initiation or dose change within the last 3 months
• Pregnant, breastfeeding or within 3 months post partum
• Irregular menstrual cycles (outside the 21-35 day window)
• Surgical menopause
• Premature ovarian insufficiency
• Other endocrine disorders e.g. uncontrolled thyroid disease, high prolactin, cushing's syndrome, polycystic ovarian syndrome)
• Regular systemic steroid use or use of other medications known to affect sex hormone within the last 3 months
• Severe mental health issues that impair consent or participation
• Needle phobic so that venepuncture is intolerable
• The use of the emergency contraceptive pill either 3 months prior to the study or during the study.