Premenstrual
Syndrome/ Premenstrual Dysphoric Disorder
by
Robert L Reid, MD
Premenstrual Syndrome, the
recurrence of luteal phase physical, psychological, and/or behavioural
changes, of sufficient severity to disrupt interpersonal relationships
and work productivity, affects between 3-5% of women of reproductive
age. Many theories have been advanced to explain this condition however
no single hypothesis has been able to account for the diverse
manifestations. Clinical observations and therapeutic trials however
lend support to the notion that psychiatric symptoms, which are
generally considered the most distressing, result when normal
fluctuations in the gonadal hormones [estrogen and progesterone] trigger
fluctuations in central neurotransmitters such as serotonin and
norepinephrine.
Several lines of evidence
support such an interrelationship between estrogen or lack of estrogen
effect (perhaps mediated by progestin induced depletion of estrogen
receptors) and central serotonergic/ noradrenergic activity. The
midcycle appearance of PMS symptoms in 5-10% of PMS sufferers coincides
with the periovulatory fall in estradiol whereas the reappearance and
ever increasing severity of symptoms in the late luteal phase may result
from progesterone-induced depletion of central estrogen receptors
coincident with the decline of estradiol leading up to menstruation . In
double-blind trials estrogen has been shown to alleviate clinical
depression in hypoestrogenic perimenopausal women. The addition of
sequential progestin therapy to estrogen replacement triggers
characteristic PMS-like mood disturbance in some susceptible
postmenopausal women. Anti-estrogens given for ovulation induction may,
at times, provoke profound mood disruption. Women with premenstrual
syndrome show a surprisingly high frequency of premenstrual and
menstrual hot flashes (85% of PMS sufferers vs 15% of non- PMS controls)
that are typical of those experienced by menopausal women. Selective
serotonin reuptake inhibitors (SSRIs) have been shown to alleviate hot
flashes. In each of these circumstances a decrease in exposure to
estrogen has been linked to mood disturbance and in each case a decrease
in serotonin activity (inferred from the response to SSRIs) appears to
be the proximate cause.
The evidence for a link
between gonadal steroids and central neurotransmitters will be reviewed
and therapeutic strategies for PMS (PMDD) reviewed.