March 16, 2007 — Long-term treatment with French maritime pine bark extract (Pycnogenol) was effective in reducing symptoms of endometriosis, such as pelvic pain and dysmenorrhea, according to the results of a study reported in the March issue of the Journal of Reproductive Medicine.

"The cause of endometriosis is unknown and treatment to fully cure endometriosis has yet to be developed," lead author Takafumi Kohama, MD, from Keiju Medical Center in Nanao City and Kanazawa University School of Medicine in Ishokawa, Japan, said in a news release. "Common hormone treatments such as gonadotropin-releasing hormone agents (Gn-RHa) may likely restrict women from becoming pregnant during treatment. Danazol, another hormone treatment, produces side effects such as ovarian deficiency, osteoporosis and obesity."

From 1999 to 2004, 58 women who had persistent symptoms after endometriosis surgery performed within 6 months before study enrollment were randomized to receive the antioxidant pine bark extract or Gn-RHa. Mean age was 33.2 ± 4.0 years (range, 21 - 38 years). Women in the pine bark extract group received 30 mg capsules by mouth twice daily, immediately after morning and evening meals, for 48 weeks. Women in the Gn-RHa group received injected leuprorelin acetate depot, 3.75 mg intracutaneously, 6 times every 4 weeks.

Regular menstruation and ovulation were confirmed for 3 months before treatment, and women were examined before and at 4, 12, 24, and 48 weeks after treatment to evaluate control of symptoms, including pain, urinary and bowel symptoms, and breakthrough bleeding. An investigator performed an interview and gynecologic examination, and pain was evaluated by patients' self-assessment.

"As expected, Gn-RHa suppressed menstruation during treatment, whereas no influence on menstrual cycles was observed in the Pycnogenol group," Dr. Kohama says. "Gn-RHa lowered estrogen levels drastically and in contrast, the estrogen levels of the Pycnogenol group showed no systematic changes over the observation period. In addition, five women in the trial taking Pycnogenol actually got pregnant."

At the start of treatment, both groups were similar in the proportion with severe pain, pelvic tenderness, and pelvic indurations. After 4 weeks, symptom scores in the Pycnogenol group were slowly but steadily reduced from severe to moderate. Overall, this group experienced a significant reduction in symptoms of endometriosis by 33%. Although the Gn-RHa had a more efficient reduction in symptom scores, relapse of symptoms occurred after 24 weeks posttreatment.

"Our results convey Pycnogenol as an extremely effective natural treatment without dangerous side effects," Dr. Kohama concludes.

J Reprod Med. 2007;52:000-000.

Clinical Context

Endometriosis, one of the most common causes of infertility and pelvic pain in women, is often treated with hormonal agents such as Gn-RHa. However, Gn-RHa suppresses estrogen levels within 2 weeks of treatment, and it typically prevents pregnancy during treatment, with variable return of ovulation and menstruation. Because the Gn-RHa leuprorelin completely blocks estrogen, adverse effects necessitate discontinuation after 24 weeks. The hormonal agent danazol is also associated with adverse events such as ovarian deficiency, osteoporosis, and obesity.

Pine bark extract is a natural plant extract of maritime pine bark containing many beneficial procyanidins, bioflavonoids, and organic acids, and evidence to date suggests that it is safe and effective in reducing dysmenorrhea and discomfort associated with menstruation and premenstrual syndrome. An earlier study showed that abdominal pain from endometriosis was reduced in 80%, and cramps disappeared in 77% of the women taking pine bark extract.

Pearls for Practice

• Pine bark extract was associated with reduced symptoms of endometriosis by about 33% overall, as well as improved specific outcomes of menstrual pain, pelvic pain, pelvic tenderness, and pelvic induration on ultrasound and magnetic resonance imaging. The Gn-RHa group had a greater reduction in symptom scores during treatment than did the pine bark extract group, but relapse of symptoms occurred after 24 weeks posttreatment, with return of symptom scores toward baseline levels.
• Women in the Gn-RHa group did not menstruate during treatment and had dramatic reduction in estrogen levels, but those in the pine bark extract group had no change in their menstrual cycles or estrogen levels.

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