Migraine Headaches Associated with the Menstrual Cycle

Up to 25% of women experience migraine headaches during their reproductive years; often migraine headaches may be triggered or exacerbated by hormonal changes.  It has been estimated that 7-14% of women experience migraines only during the premenstrual or menstrual phase of their cycles.  Another 52-70% experience headaches throughout the month but note increased headache activity before or during menses. 

Interestingly, before puberty, the prevalence of migraine appears to be similar for boys and girls.  Peak migraine incidence in girls occurs at menarche, and in adulthood females outnumber male migraine sufferers by about 3 to 1. 

The reported effects of pregnancy, oral contraceptives and menopause on migraine headache patterns have been variable.  It is believed that declining estrogen levels may be an important trigger, and it is thought that progesterone may also play a role.  Migraine often, but not always, improves during pregnancy; however, postpartum migraine flares are common.  The effects of oral contraceptive use are quite variable: migraines may improve, worsen, or remain the same.  Low estrogen dose oral contraceptives usually have no effect or may improve migraine. Estrogen replacement therapy for menopausal women often exacerbates migraines. 

Treatment options include aspirin, ibuprofen, or acetaminophen, often combined with caffeine, for mild attacks.  Triptans (including sumatriptan) or DHE (dihydroergotamine) may be used for moderate to severe attacks.  Migraine prophylactic agents include beta-blockers, calcium channel blockers, tricyclic antidepressants, anti-epileptic agents, and serotonin receptor antagonists.  For menstrual migraines, estradiol-containing compounds medications (oral, transdermal or percutaneous gel) may be used to prevent migraines.  Progesterone alone appears to have little therapeutic value. 

In general, it is helpful for a woman experiencing new onset or exacerbation of migraine to seek consultation from a neurologist. 

Kimberly H. Pearson, MD

Read more:

Women’s Mental Health.  Kornstein SG, Clayton AH.  The Guilford Press:  New York.  2002.

Brandes JL. The influence of estrogen on migraine: a systematic review. JAMA. 2006 Apr 19;295(15):1824-30.

Loder EW. Menstrual migraine: pathophysiology, diagnosis, and impact. Headache. 2006 Oct;46 Suppl 2:S55-60.

Obesity Linked to Postpartum Depression Risk

Previous studies have linked postpartum depression (PPD) to numerous risk factors, including depression during pregnancy, a history of depression prior to pregnancy, as well as marital problems, recent stressful events, and inadequate social supports.

Research conducted at the University of Utah in Salt Lake City now suggests that obesity may place women at increased risk of postpartum depression, as presented in a poster at the annual meeting for the Society of Maternal-Fetal Medicine. In their study of 1282 women who gave birth to singleton infants, the risk of screening positive on the Edinburgh Postnatal Depression Screen 8 weeks after delivery increased dramatically for women with a pregnancy body mass index (BMI) greater than 35. They also noted that women at the extremes of body mass index and those with greater weight gain during pregnancy were at increased risk for postpartum depression.

	BMI	Positive for PPD
Underweight	Under 18.5	18.7%
Normal Weight	18.5-24.9	12.7%
Overweight	15-19.9	15.9%
Class I Obesity	30-34.9	17.6%
Class II Obesity	35-39.9	28%
Class III Obesity	40 or greater	29.4%

Increased BMI was a risk factor even after controlling for maternal age, race, number of children, education, and other stressors such as financial stressors and partner-related stressors. It is important to note that there were far fewer women in the class II obesity and class III obesity groups than in the other groups.

This is first study to use a validated screening tool to look at the relationship between maternal BMI and postpartum depression. As more research in this field develops, it is our hope that we will be better able to identify patients at risk for postpartum depression in the future.

Betty Wang, MD

Learn more:

Beck CT. Predictors of Postpartum Depression: an update. Nurs Res 50(5): 275-85, 2001

LaCoursiere DY, Baksh L, Bloebaum L, Barner MW. Maternal body mass index and self-reported postpartum depressive symptoms. Matern Child Health J 2006; 10(4): 385-90.

Poster session by Dr. Yvette LaCoursiere and colleagues at the University of Utah, Salt Lake City at the annual meeting of the Society for Maternal Fetal Medicine, as reported in: Wendling, Patrice: Obesity Linked to Postpartum Depression Risk. Clinical Psychiatry News 36 (3): 18-19, 2008.

Acupuncture for the Treatment of Menopausal Hot Flushes

Many women report vasomotor symptoms, including hot flushes and night sweats, during the menopausal transition. While estrogen is clearly one of the most effective treatments for vasomotor symptoms, recent concerns regarding the use of hormone replacement therapy (HRT) have made treaters much more reluctant to recommend HRT, even for short-term management of vasomotor symptoms. A recent study has demonstrated that acupuncture may be an effective non-hormonal treatment for vasomotor symptoms.

In this prospective study conducted in Sweden, 102 postmenopausal women were recruited for two studies performed in parallel. In the first study, women were randomized to receive either transdermal estrogen or placebo. In the second study, women were randomized to three groups and received oral estrogen, acupuncture or applied relaxation for 12 weeks. Menopausal symptoms were measured with daily logs.

The number of hot flushes in a 24 hour period decreased significantly after 4 and 12 weeks in all treatment groups. Both at 4 and 12 weeks, acupuncture decreased the number of flushes more than placebo. Scores on the Kupperman menopausal index decreased in all groups except the placebo group.

While the results of this study are encouraging, other studies have yielded mixed results. A study conducted at Stanford University demonstrated that acupuncture was more effective than placebo in reducing both the severity and frequency of hot flushes in a group of postmenopausal women.

Another study of hot flushes in breast cancer patients did not show acupuncture to be effective. A third study in menopausal women was also negative, although this study was much shorter in duration (with only 5 weeks of active treatment).

Ruta Nonacs, MD PhD

Zaborowska E, Brynhildsen J, Damberg, S et al. Effects of Acupuncture, Applied Relaxation, Estrogens and Placebo on Hot Flushes in Postmenopausal Women: an Analysis of Two Prospective, Parallel, Randomized Studies. Climacteric 2007 ;10(1):38-45. (Click here for full text)

 

 

Untreated Maternal Depression: What is the Impact on the Unborn Child?

Depression during pregnancy is common. While concerns have been raised regarding the potential teratogenic and long-term neurobehavioral effects of psychotropic drug use during pregnancy, what is often overlooked is the fact that untreated maternal depression may also put the unborn baby at risk. 

Maternal depressive symptoms during pregnancy have been shown to be associated with a variety of adverse pregnancy outcomes.  Several studies have described low birth weight and fetal growth retardation in children born to depressed mothers.  In one study, this effect was seen only in women from lower income households and was greatest if the woman experienced depression in the late second trimester or early third trimester (Hoffman and Hatch, 2000).  

Preterm delivery is another potential pregnancy complication among women experiencing distress during pregnancy (Rondo et al. 2003).  In one study of African-American women, those who had higher depression scores also had a higher incidence of spontaneous preterm delivery (Orr et al. 2002).  In another study, spontaneous preterm labor was significantly associated with high depression scores in a sample of underweight women (body mass index below 19) (Dayan et al. 2002).  A more recent report by the same authors showed an association between depressive symptoms and preterm birth in a population of European women (Dayan et al. 2006).

Pregnancy complications related to maternal depression in late pregnancy have also been described, including an increased risk for having epidural analgesia, operative delivery, and infant admission to a special care nursery for a variety of conditions including respiratory distress, hypoglycemia, prematurity, and maternal diseases (Chung et al, 2001).  Another study showed that the risk for preeclampsia was greater in women who experienced depression in early pregnancy, from 10 to 17 weeks gestation (Kurki et al, 2000).

These data underscore the need to perform a thorough risk/benefit analysis of pregnant women with depression, including evaluating the impact of untreated depression on the baby and the mother, as well as the risks of using medication during pregnancy.

Laura Petrillo, MD

Read more:

Review in Canadian Family Physician (Bonari et al, 2004)

Top Ten Posts on the Women’s Mental Health Blog

Since the launch of our blog we’ve addressed many issues and questions in the field of Women’s Mental Health. Compiled below is a list of our most popular blog posts, on topics ranging from the safety of psychotropic drug use during pregnancy to postpartum depression.

1. Can Women Suffer from Postpartum Depression after Miscarriage? - Oct. 19, 2006

2. Cognitive Therapy vs Medication in the Treatment of Depression – Nov. 26, 2007

3. Use of Wellbutrin (Bupropion) During Pregnancy – Feb. 20, 2007

4. How to Treat Anxiety Symptoms During Pregancy – Dec. 11, 2007

5. Antidepressant-Induced Sexual Side Effects – Oct. 1, 2007

6. Treatment of Insomnia During Pregnancy – Nov. 19, 2007

7. Lamotrigine and Breastfeeding – Nov. 18, 2005

8. Evaluating the Long-Term Effects of Prenatal Antidepressant Exposure – Feb. 20, 2007

9. Interaction Between Birth-Control Preparations and Anti-Epileptic Medications – Dec. 6, 2007

10. Evaluating the Safety of First-Trimester Exposure to Lamotrigine (Lamictal) – July 11, 2006

Hormone Replacement Therapy Revisited

As a result of dramatically increased life expectancies in industrialized countries, healthy women today expect to spend nearly 40% of their lives after menopause. For these postmenopausal women, lack of estrogen may contribute to long-term adverse effects, including cardiovascular disease and osteoporosis.  Many postmenopausal women might benefit from hormone replacement therapy (HRT) with estrogens and progestins; however, a number of recent studies in the USA and Europe suggest that the potential risks of hormonal replacement therapy may sometime exceed the expected benefits. Thus, many treaters now avoid the use of hormone replacement therapy in peri- and postmenopausal women.

Conjugated equine estrogen (found in Premarin and Prempro) has been the estrogen preparation most widely used in hormone replacement therapy in postmenopausal women.  More recently, synthetic estradiols have been available in Europe and the U.S. and have been used both in both oral and transdermal (patch) preparations. Orally administered estrogen preparations, in contrast to estradiol administered transdermally, are subject to hepatic metabolism and typically result in 4 to 5 times greater estradiol concentrations.

Progestogens (progesterone or a synthetic form of progesterone) are typically used in combination with estrogens to protect the uterus and to prevent the risk of the endometrial and ovarian cancer.  Progesterone analogues, known as progestins, are now widely used in HRT.  These are synthetic compounds with progesterone-like effects on the uterus, but their chemical structures differ from natural progesterone. The oral route of administration is preferred for all compounds. Progesterone, but not the synthetic progestins, have been found to have protective cardiovascular effects, while also down-regulating the breast tissue estradiol receptors in normal and cancerous cells.

All estrogen formulations and modes of administration have similar beneficial effects on vasomotor and urogenital menopause symptoms and on bone structure. However, experimental studies and clinical trials indicate that the adverse effects of hormone replacement therapy may depend on the estrogen/progesterone formulation, dosage, mode of the administration, and the duration of the treatment.  A woman’s age and comorbid medical illnesses may also be important factors. 

Moreover, estrogens may exert different effects on certain tissues, depending on the type of estrogen and its mode of administration. For example, oral estrogens influence carbohydrate metabolism and may lead to insulin resistance, an effect not observed with transdermal estradiol.  Interestingly, when compared with the transdermal formulation, oral estrogens induce greater lipid oxidation, and may increase body mass index (BMI). Oral and transdermal estrogens both increase HDL (“good”) cholesterol, while decreasing the LDL (“bad”) cholesterol. Oral, but not transdermal, estrogens, raise circulating levels of the coagulation factors and increase C-reactive protein, a marker of cardiovascular morbidity. Both oral and transdermal estrogen preparations are shown to elevate the risk of uterine and ovarian cancer. Cardiovascular, thromboembolic and invasive breast cancer risks appear to be higher in women taking oral estrogen than in those using transdermal estradiol.  Risks are also higher in those women taking estrogen in combination with progestin compounds (as opposed to those using oral micronized progesterone).

Based on these finding, it appears that for postmenopausal women who do need HRT, a combination of transdermal estradiol and micronized progesterone would be the best choice. Studies are under way, comparing the effects of transdermal versus oral estrogen in younger postmenopausal women (KEEPS: Kronos Early Estrogen Prevention Study, Dr. Michael Harman et al., Kronos Longevity Research Institute; ELITE: Early versus Late Intervention Trial with Estradiol, Dr. Howard Hodis et al., Keck School of Medicine, University of Southern California).

Snezana Milanovic, MD MSc

References:

Brody JA, Grant MD, Frateschi LJ, Miller SC, Zhang H. Reproductive longevity and increased life expectancy. Age Ageing. 2000 Jan; 29(1):75-8.

Caufriez A. Hormonal replacement therapy (HRT) in postmenopause: a reappraisal. Ann Endocrinol (Paris). 2007 Sep;68(4):241-50. Epub 2007 Jul 24. Review.

Ho KK, O’Sullivan AJ, Wolthers T, Leung KC. Metabolic effects of oestrogens: impact of the route of administration. Ann Endocrinol (Paris). 2003 Apr;64(2):170-7. Review.

Desvenlafaxine for the Treatment of Menopausal Hot Flushes

Last Friday, Wyeth received FDA approval for the antidepressant desvenlafaxine succinate (marketed under the name Pristiq), a metabolite of venlafaxine or Effexor. Although this drug was approved for the treatment of major depression, a recent study has demonstrated that desvenlafaxine could be an effective treatment for vasomotor symptoms in postmenopausal women.

Many women report vasomotor symptoms, including hot flushes and night sweats, during the menopausal transition. While estrogen is clearly one of the most effective treatments for vasomotor symptoms, recent concerns regarding the use of hormone replacement therapy (HRT) have made treaters much more reluctant to recommend HRT, even for short-term management of vasomotor symptoms.

Depression is More Common in Women with High Risk Pregnancies

Epidemiologic studies suggest that about 10% to 15% of women suffer from clinically significant depressive symptoms during pregnancy. Little is known, however, about the prevalence of depression among women with high risk pregnancies. A recent study published online in the Journal of Clinical Psychiatry suggests that this population may be at significant risk for antenatal depression.

129 women hospitalized for high risk pregnancies were assessed using a variety of instruments, including the Edinburgh Postnatal Depression Scale (EPDS) and the Dyadic Adjustment Scale (DAS). Obstetric complications were classified according to the Hobel Risk Assessment for Prematurity.

• 44.2% of the women (57/129) had clinically significant depressive symptoms, with a score of 11 or greater on the EPDS.

• 19.4% of the women (25/129) met the DSM-IV criteria for major depressive disorder.

• Mothers reporting strong attachment to the unborn child experienced less severe depressive symptoms.

• Women reporting relationship difficulties were more likely to experience more severe depressive symptoms.

• The severity of the obstetric complication did not appear to correlate with the severity of depressive symptoms; however, one type of complication – incompetent cervix – was more strongly associated with depressive symptoms.

Vote for The Center for Women’s Mental Health in the Blogger’s Choice Awards

Our blog has been nominated for Best Health Blog for the 2008 Blogger’s Choice Awards. We are very excited about this nomination and hope that being voted one of the top blogs in the health field will introduce more people to the important issues in perinatal and reproductive psychiatry.

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Thank you for your support.

The MGH Center for Women’s Mental Health

 

Medication Changes During Pregnancy

At our clinic we have the opportunity to see patients at various stages of pregnancy. When we evaluate a patient while she is still in the planning stages, we may recommend changing medications to those that have a better studied safety profile during pregnancy and see how she does on those medications prior to conception. If that same patient came into our clinic for an evaluation, but was already pregnant, we may make different recommendations than if she was in the planning stages.

Many clinicians are especially concerned about the first trimester, the time when congenital malformations may occur. Even during this critical period, it is often recommended that the patient continue the medication she has done well on, given the risk of relapse associated with discontinuation of medications and the risk of changing to a medication that she has never taken before. This means that if a patient is already pregnant and is doing well, we often recommend staying on the current medication regiment, even if there is little safety information available during pregnancy on a particular medication.