Does Dietary Fatty Acid, Decanoic Acid, Prevent Polycystic Ovary Syndrome?

The polycystic ovary syndrome (PCOS), which combines with multiple endocrine dysfunctions, affects 6% of women in worldwide and results in health complications throughout life including hirsutism, reproductive dysfunction, and metabolic syndromes (1, 2). Because of the heterogeneity of the POCS, treatments and managements have been controversial in medical disciplines. The major endocrine disturbance in PCOS is excessive androgen secretion or activity. In normal reproductive age, the ovarian theca cell synthesizes androgens in response to stimulation of LH, whereas the granulosa cell converts androgenic precursors into estrogens under the stimulation of FSH (3). The appropriate levels of LH and FSH are fine-tuned in the normal individual, whereas the concentration of LH is relatively higher than FSH in PCOS-affected women and their theca cells are more efficient at converting androgenic precursors to T than normal theca cell (Figure 1) (3). In clinics, antiandrogens have been successfully used to treat hirsutism and acne in PCOS patients. However, general concerns have been raised upon the side effects of antiandrogens including hair loss, hepatocellular toxicity, and feminization of male fetuses (4, 5). In addition to hyperandrogenism, a large number of PCOS-affected women were also affected by metabolic syndromes, especially hyperinsulinemia or insulin resistance (1, 3). Although the underlying mechanisms of how hyperinsulinemia or insulin resistance affects PCOS are not clear, it is greatly appreciated that insulin sensitizers improve symptoms in PCOS patients (3–5). For example, the insulin-sensitizing agent metformin increased the ovulatory response to the antiestrogen reagent clomiphene in obese PCOS women (2). Because there is reciprocal interaction between insulin and T (6, 7), metformin may directly or indirectly inhibit both insulin and androgen secretion. However, metformin treatment results in vicious side effects such as diarrhea, side pain, and sensory discomfort. Therefore, alternative approaches are needed for the treatment and management of PCOS. In this issue of Endocrinology, Lee et al (8) propose a promising approach to treat PCOS using a dietary decanoic acid (Figure 1). Decanoic acid is a nontoxic fatty acid that contains 10 carbon molecules and occurs naturally in coconut oil and palm oil (9). To mimic the activation of LH signaling, Lee et al treated human adrenocortical cells with cAMP, a downstream mediator of LH signaling. As expected, the treatment of cAMP increased productions of T and 3 -hydroxysteroid dehydrogenase (3 -HSD), a key enzyme of androgen synthesis. Both metformin and decanoic acid attenuated cAMP-stimulated androgen synthesis back to normal level in vitro, and this inhibition is dependent on the attenuation of Nur77 recruitment on the promoter of 3 -HSD. In a letozole-induced rat PCOS model, only decanoic acid but not metformin diminished extra levels of 3 -HSD and androgen and completely restored the estrous cycle. Furthermore, decanoic acid treatment also improved the glucose sensitivity without gaining the weight in a diabetic mouse model (10). These findings suggest a dietary decanoic acid could be beneficial for the managements of both hyperandrogenism and insulin resistance in PCOS patients. The advantages of decanoic acid treatment compared with antiandrogens and insulin sensitizers are evident: nontoxic, nonobese, and nonhormonal involvement. Yet to apply the decanoic acid in human PCOS patients, the following questions need to be addressed in the future