Effect of progesterone therapy on arginine vasopressin and atrial natriuretic factor in premenstrual syndrome.

OBJECTIVES

To explore the possible role of natriuretic peptides and vasopressin in luteal phase fluid retention in premenstrual syndrome (PMS) and to determine the effect of progesterone therapy on these hormones.

DESIGN

Self-controlled prospective study.

SETTING

University-based medical research centre.

PATIENTS

Six patients with PMS were studied 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 administered on an early follicular and a late luteal phase day in 2 menstrual cycles. Progesterone was administered orally during the second luteal phase.

OUTCOME MEASURES

Osmolality, arginine vasopressin (AVP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP) levels in plasma, osmolality, sodium, potassium, cyclic adenosine monophosphate (cAMP) and cyclic guanosine 5'-phosphate (cGMP) concentrations in urine, and thirst sensation.

RESULTS

Mean basal plasma ANF and osmolality levels and the threshold for AVP release and thirst were lower, and mean urinary cyclic nucleotide levels and AVP sensitivity (amount 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 urinary sodium and cyclic nucleotide levels. Plasma ANF and osmolality levels remained lower in the luteal phase compared with the follicular phase, but AVP levels at the end of the saline infusion were higher in the luteal phase than in the follicular phase. Progesterone therapy caused an increase in plasma ANF and osmolality levels and the AVP threshold and a decrease in AVP levels and sensitivity and urinary cyclic nucleotide levels. BNP levels did not change with phase or treatment. The differences in AVP threshold with phase and treatment were statistically significant (p < 0.001). There was a significant phase effect for plasma ANF (p = 0.02) and a significant or near-significant interaction effect of phase and treatment for plasma ANF (p = 0.06) and urinary cAMP (p = 0.047) and cGMP (p = 0.066). The effect of phase and treatment 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 inhibition of AVP release or synthesis.