EFFECT OF PROGESTERONE THERAPY ON ARGININE-VASOPRESSIN AND ATRIAL-NATRIURETIC-FACTOR IN PREMENSTRUAL-SYNDROME

Objectives: To explore the possible role of natriuretic peptides and v asopressin in luteal phase fluid retention in premenstrual syndrome (P MS) and to determine the effect of progesterone therapy on these hormo nes. Design: Self-controlled prospective study. Setting: University-ba sed medical research centre. Patients: Six patients with PMS were stud ied during the symptomatic luteal and asymptomatic follicular phases. The follicular phase response was used as the control for each subject . Interventions: An intravenous infusion of 3% saline solution was adm inistered on an early follicular and a late luteal phase day in 2 mens trual cycles. Progesterone was administered orally during the second l uteal phase. Outcome measures: Osmolality, arginine vasopressin (AVP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) levels in plasma, osmolality, sodium, potassium, cyclic adenosine mono phosphate (cAMP) and cyclic guanosine 5'-phosphate (cGMP) concentratio ns in urine, and thirst sensation. Results: Mean basal plasma ANF and osmolality levels and the threshold for AVP release and thirst were lo wer, and mean urinary cyclic nucleotide levels and AVP sensitivity (am ount of AVP secreted per unit rise in plasma osmolality) were higher, in the luteal phase than in the follicular phase. With saline loading, there was an increase in plasma osmolality, AVP and ANF and in urinar y sodium and cyclic nucleotide levels. Plasma ANF and osmolality level s remained lower in the luteal phase compared with the follicular phas e, but AVP levels at the end of the saline infusion were higher in the luteal phase than in the follicular phase. Progesterone therapy cause d an increase in plasma ANF and osmolality levels and the AVP threshol d and a decrease in AVP levels and sensitivity and urinary cyclic nucl eotide levels. BNP levels did not change with phase or treatment. The differences in AVP threshold with phase and treatment were statistical ly significant (p < 0.001). There was a significant phase effect for p lasma ANF (p = 0.02) and a significant or near-significant interaction effect of phase and treatment for plasma ANF (p = 0.06) and urinary c AMP (p = 0.047) and cGMP (p = 0.066). The effect of phase and treatmen t was not significant for the other measurements. Conclusions: Luteal phase fluid retention may be due to a relative deficiency of ANF and a lower threshold for AVP release. The symptomatic improvement produced by progesterone treatment may be due to its stimulation of ANF and in hibition of AVP release or synthesis.