Clinical Briefs

With Comments from Russell H. Greenfield, MD. Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC; and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ.

Pycky, Pycky — French Maritime Bark and Menopause

Source: Yang HM, et al. A randomized, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in peri-menopausal women. Acta Obstet Gynecol. 2007;86:978-985.

Goal: To determine whether or not a standardized extract of French maritime bark (Pinus pinaster, Pycnogenol) is effective for the relief of climacteric symptoms.

Design: Randomized, double-blind, placebo-controlled clinical trial.

Subjects: Peri-menopausal Taiwanese women aged 45-55 years (n = 200, data evaluable for n = 155).

Methods: All participants underwent an initial history and physical examination, during which demographic and behavioral data were obtained, and mammography, Pap testing, and vaginal sonography were performed. Blood tests were also obtained, including total antioxidant status (TAS), and FSH and estrogen levels were taken on the third day of menstruation. Subjects received 100 mg Pycnogenol or placebo twice daily (total of 200 mg Pycnogenol). Follow-up evaluations occurred after 1, 3, and 6 months. Climacteric symptoms were evaluated using the Women's Health Questionnaire (WHQ), and blood tests were obtained to check routine chemistry profiles and antioxidant status.

Results: A total of 175 participants completed the 6-month protocol, but only 155 completed all assessments. Rapid improvement in all climacteric symptoms was noted after one month in the group receiving Pycnogenol, with frequency of symptoms decreasing continuously during treatment. TAS and LDL/HDL ratio also improved over the course of the trial. In the placebo group, there was improvement noted only for the question regarding memory. No side effects were reported with Pycnogenol use.

Conclusions: Pycnogenol may be an effective option for treating climacteric symptoms.

Study Strengths: Subjects were contacted weekly for the first 3 months, then once every 2 weeks, to help ensure compliance and check for side effects.

Study Weaknesses: No statistical analysis (reportedly the benefit was so great that none was necessary); attrition rate (22.5%); spelling errors (it happens, but still!).

Of Note: All subjects had a history of disappearance of menses for 3-11 months, with subsequent return of normal cycles; subjects reported their most bothersome symptoms were not vasomotor in origin but fatigue, headache, and anxiety; Pycnogenol reportedly contains low concentrations of procyanidins and phenolic acids; some data suggest Pycnogenol could benefit memory, as well as skin elasticity; there was no reported potential conflict of interest reported.

We Knew That: Desire for relief of vasomotor symptoms (hot flashes and sweating) is the most commonly reported reason women going through menopause seek medical attention; other symptoms commonly experienced during menopause include fatigue, mood alterations, decreased libido, cognitive issues, and urogenital symptoms; concerns about estrogen replacement therapy have caused many patients and physicians to seek out safe alternatives for the treatment of climacteric symptoms; extracts of Pycnogenol have been found to stimulate endothelial production of nitric oxide and to have potent antioxidant potential.

Clinical Import: The potential health benefits of extracts from French maritime bark have been studied and promoted for years, but this is one of the first to apply the agent to postmenopausal issues. The findings are very strong, even in light of the omission of important data. Stating that no statistical analysis was warranted because of the success of the intervention, however, creates an unacceptable level of doubt regarding the findings, and relegates them to the realm of "interesting, but requires further study." Practitioners cannot feel confident recommending Pycnogenol for symptoms of menopause on the basis of this paper alone.

What to do with this article: Keep a copy of the abstract on your computer.


Anxious Hearts — Anxiety and CVD

Source: Smoller JW, et al. Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study. Arch Gen Psychiatry. 2007;64:1153-1160.

Goal: To prospectively examine whether panic attacks are associated with risk of cardiovascular morbidity and mortality and all-cause mortality in postmenopausal women.

Design: Prospective cohort survey.

Subjects: Generally healthy, community-dwelling, postmenopausal women (ages 51-83 years of age, n = 3369) enrolled in the Myocardial Ischemia and Migraine Study (MIMS) who completed a questionnaire about occurrence of panic attacks in the prior 6 months.

Methods: Subjects completed a questionnaire at baseline, and again annually, as well as undergoing initial physical examination and blood test evaluation, that was then repeated every 3 years. MIMS participants completed a questionnaire about occurrence of panic attacks in the previous 6 months. A Medical History Update Questionnaire was mailed annually, and medical records reviewed as necessary. The mean period of follow-up was 5.3 years. Principle outcome measures were fatal and non-fatal myocardial infarction and stroke and all-cause mortality.

Results: Ten percent of the cohort had a history of full-blown panic attacks in the prior 6 months. Participants who experienced at least 1 panic attack in the previous 6 months were, at baseline, more likely to be smokers, have depressive symptoms, and have a higher body mass index, as well as a history of diabetes and hypertension. A total of 41 fatal or non-fatal MIs, 40 strokes, and 147 deaths from all causes were identified. Full-blown panic attacks were associated with both coronary heart disease (hazard ratio = 4.20) and the combined end point of coronary heart disease or stroke (hazard ratio = 3.08). Excluding those with a history of cardiovascular/ cerebrovascular disease, the hazard ratio for all-cause mortality among women with panic attacks was 1.75.

Conclusions: Among postmenopausal women, panic attacks are relatively common, and may be an independent risk factor for heart disease and stroke.

Study Strengths: Prospective nature; controlled for multiple potential confounders; proxy respondents contacted for subjects not responding to mailed questionnaires.

Study Weaknesses: Self-reporting; limited measures; cross-sectional nature.

Of Note: Phobic anxiety can be categorized as the unreasonable fear of situations, such as enclosed spaces, crowds, incurable illness, and being alone; panic attacks involve sudden episodes of fear or anxiety accompanied by 4 or more associated cognitive or autonomic symptoms; the WHI Observational Study is an ongoing prospective, multi-center study to assess risk factors for heart disease, cancer, fractures, and other causes of morbidity and mortality among postmenopausal women; the objective of the MIMS study was to investigate relationships between migraine, panic symptoms, and ischemia, as measured on 24-hour ambulatory ECG monitors; limited-symptom panic attacks were associated with non-significant increases in cardiovascular morbidity and mortality.

We Knew That: Recent studies suggest that panic attacks are common among postmenopausal women; research suggests a strong association between depression and/or phobic anxiety with cardiovascular morbidity and mortality; one study of > 30,000 male health professionals aged 42-77 years showed that those with high levels of phobic anxiety had a 6-fold increase in risk of sudden death; the Nurses' Health Study found that among relatively healthy women (mean age 54 years), a high level of phobic anxiety was associated with increased risk for fatal coronary heart disease.

Clinical Import: This is a beautifully designed paper whose conclusions underscore knowledge that cannot be ignored: the fact that numerous emotional and psychiatric states can contribute adversely to the risk for cardiovascular disease. The mechanisms by which emotional/spiritual states might impact cardiovascular health remain elusive, but the risk is real. The authors are thorough in their review of the topic, referencing studies that noted adverse cardiovascular consequences associated with such states as anger and chronic worry. What is striking and disappointing, however, is what is not mentioned. The authors close their paper by stating "... older women with a recent history of panic attacks represent a subgroup at elevated risk of MI and stroke in whom careful monitoring and cardiovascular risk reduction may be particularly important." Nowhere in this otherwise excellent paper is there any mention of stress management intervention, no mention of mind/body therapies, no mention of the potential benefit of preventive strategies. The authors have crafted an important paper, but leave us wanting in the end.

What to do with this article: Keep a hard copy in your file cabinet.