Hormones Complicate Women’s Treatment

Once children become adults, risk factors change. Margaret Altemus, M.D., an associate professor of psychiatry at Weill Medical College of Cornell University in New York, has studied the hormonal and sex-related issues of anxiety in women.

As women move through their life cycle, there is much hormonal variation during their menstrual cycles and childbearing years, said Altemus.

Anxiety may present only in the luteal phase or more generally as an exacerbation of preexisting illness, she said. Several treatments can be used for luteal-phase symptoms like tension, hypersensitivity to stimuli, or irritability.

Both SSRI antidepressants and placebos lower premenstrual symptoms within three hours of administration, said Altemus, but only SSRI treatment maintains that reduction beyond three hours.

Benzodiazepines or oral contraceptives with drosperinone taken during the luteal phase may help. Calcium (600 mg bid) across the cycle appears to help. There are no published trials of vitamin D for reducing anxiety, although there is a drop in levels of the vitamin during the premenstrual week, and there is some indication that 2,000 IU/day of vitamin D reduces symptoms of premenstrual syndrome. Continuous-hormone contraceptives may help eliminate hormonal shifts. Exercise may be effective at reducing premenstrual syndrome symptoms, too.

Physicians treating anxiety in premenopausal women must always assume the possibility of pregnancy, especially since 50 percent of pregnancies are unplanned, said Altemus.

In cases in which preexisting anxiety is exacerbated during the premenstrual period, Altemus recommend using full-cycle treatments, increasing the SSRI or dose, or using psychotherapy.

Generally, many women want to minimize medication use during pregnancy, but they and their physicians should carefully weigh the potential effects of anxiety as well as medication on the fetus or baby. Nontreatment of anxiety may lead, in some cases, to less adherence to prenatal care, poor nutrition, and even prematurity.

If the decision is to stop medication, it is best to taper patients off gradually and substitute psychotherapy to compensate.

The bulk of the evidence supports use of sertraline or paroxetine during pregnancy; teratogenic risk of antidepressants and benzodiazepines is very low, she said. However, about 50 percent of newborns exposed in utero to SSRIs exhibit transient irritability and increased startle. Higher maternal doses of benzodiazepines may leave the newborn with irritability or respiratory difficulties, and any cognitive effects are unknown.

During lactation, drug levels in breast milk are about equal to those in the blood and so are ingested by the baby at lower levels (after metabolism) than in pregnancy. Medications with a short half-life may be preferred. If desired, women may forgo or reduce breastfeeding to lessen the baby’s exposure.

If the decision is made to wean the baby, the weaning should be done gradually, according to Altemus. Animal studies and some research in humans suggest that rapid weaning may worsen anxiety.

Risks of anxiety may increase after age 45 or following ob/gyn treatments like surgically or drug-induced menopause, use of beta-agonists to stop premature labor, or use of metaclopramide to stimulate milk production.

Short-term hormonal replacement can relieve depression during perimenopause, but not after menopause, she said.