Flaxseed oil stimulates gynecomastia

Abstract

Flaxseed oil contains lignans, which exhibit anti-inflammatory and antiatherogenic activities. A 70-year-old male patient presented to our office due to hyperlipidaemia and started to take a tablespoon of flaxseed oil daily. Three months later, he reported left breast swelling and pain. Although the echogram revealed a tumour in the left mammary gland, the breast biopsy was compatible with gynecomastia, showing ductal hyperplasia without evidence of malignancy. His breast epithelia were oestrogen receptor-positive. Potential role of phytoestrogens was discussed.

Background

Flaxseed oil contains lignans, which exhibit anti-inflammatory and antiatherogenic activities.¹ Thus, though flaxseed oil seems effective for antiaging, it may lead to unfavourable reactions in children and women, especially during pregnancy. Previous studies cautioned the consumption of flaxseed during pregnancy and lactation.² Here, we report an adverse reaction of flaxseed oil in men. In our knowledge, this is the first report that flaxseed oil could induce breast tissue growth.

Case presentation

A 70-year-old male patient presented to our office due to hyperlipidaemia and chronic kidney disease 9 years ago. High-density and low-density cholesterol (LDL-C) were 51 and 185 mg/dL, respectively. He had acute glomerulonephritis during childhood. His father had hyperlipidaemia and died following myocardial infarction. His urinalysis and blood pressure were unremarkable. His estimated glomerular filtration rate was slightly reduced (47 mL/min/1·72 m²). Although a dietician advised him of dietary modifications, his LDL-C remained high (181 mg/dL) after 6 months. We prescribed atorvastatin 10 mg/day,³ which lowered LDL-C to 98 mg/dL without any side effects, and we continued the medication.

Outcome and follow-up

Almost 9 months ago, he started to take a tablespoon of flaxseed oil daily. He reported left breast swelling and pain 6 months ago. Physical examination revealed a mass in his left breast. He was referred to a surgeon, and the echogram revealed a tumour in the left mammary gland (figure 1A). To rule out malignancy, a breast biopsy was performed. Biopsy specimen was compatible with gynecomastia, showing ductal hyperplasia without evidence of malignancy (figure 1B). Although Ki67 prevailed in epithelial cells, CK5/6-positive and p63-positive cells were distributed normally (figure 1C, E, H). Normal alignment of the smooth muscle actin at the ductal base indicated no invasion of the tumour into the surrounding tissue (figure 1I). We recommended him to stop atorvastatin,⁴ which he deferred; however, he agreed to stop taking flaxseed oil. Three months later, he was free of breast pain and swelling, with no palpable mass. He continued to take atorvastatin and denied restarting flaxseed oil.

Figure 1.

Summary of breast mass images. (A) Echography shows a space-occupying lesion (1·6×1·8 cm) beneath the nipple. (B) Microscopic image of biopsy specimen exhibiting ductal hyperplasia with papillary formation (HE,×400). (C) Immunohistochemistry revealed that CK5/6-positive cells were normally distributed, located in the epithelial base and papillary tip (peroxidase). (D) Most epithelial cells are positive for oestrogen receptors. (E) p63-positive cells are normally located at the epithelial base. (F) Progesterone receptors are present in most epithelial cells. (G) This epithelium is negative for human epidermal growth factor receptor 2. (H) Approximately 20% of cells are Ki67-positive. (I) Normal alignment of smooth muscle actin at ductal base suggests no invasion of the tumour into the surrounding tissue.

Discussion

Lignans include phytoestrogens, such as pinoresinol, secoisolariciresinol, matairesinol and lariciresinol.¹ Intestinal bacteria convert them to enterolignans, enterodiol and enterolactone. Daily consumption of 5–10 g flaxseed increases urinary excretion of enterodiol and enterolactone 3–285 times. Enterolignans behave like selective oestrogen receptor (OR) modulators. A significant inverse relationship was found between serum enterolactone and breast cancer risk, which was stronger for OR-negative, progesterone receptor (PR)-negative than for OR-positive PR-positive tumours; however, there was no difference based on the expression of human epidermal growth factor receptor (HER)2, in postmenopausal women.⁵ His breast epithelia were OR-positive, PR-positive and HER2-negative (figure 1D, F, G). Lignans reduce Ki67 expression in benign breast tissue in women, decreasing breast cancer risk in premenopausal women.^{6 7} However, Ki67 expression was high in our case, suggesting proliferative changes. Thus, phytoestrogens may play a role in growing breast tissue rather than suppressing it in this case. Statins reduce testosterone levels,⁴ presumably leading to a synergistic effect in inducing gynecomastia. Of note, the recent report suggested that lignans did not reduce the risk of endometrial cancer.⁸ This case is alarming because although flaxseed oil can be used for health promotion, it may lead to unfavourable reactions in men as well as children and women.

Patient’s perspective.

I gave a consent for publishing my data because I would not like the other people to experience unpleasant adverse reactions.

Learning points.

• Ligans can induce gynecomastia, with tumourous lesion.

• Flaxseed oil does not reduce Ki67 expression in male normal breast tissue.

• Statin may not mediate gynecomastia in all cases of patients with hyperlipidaemia.