Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder – “the female metabolic syndrome” – associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. The precise aetiology of the disease is unknown. A potential contribution of the sympathetic nervous system as a primary factor in the development and maintenance of PCOS has been suggested.

The present lecture will discuss the sympathetic innervation of the ovaries in normal and polycystic ovaries (PCO). Sympatheic nervous system involvement is supported by the greater density of catecholaminergic nerve fibres in PCO ^[1,2]. Increased ovarian sympathetic nerve activity might contribute to PCOS by stimulating androgen secretion ^[3]. This would explain why ovarian wedge resection or laparoscopic laser cauterization ^[4], which likely disrupt ovarian sympathetic innervation, increase ovulatory responses in women with PCOS.

Acupuncture, a treatment that dates back 3000-5000 years, has become more established in Western medicine as a complement or alternative to conventional therapies. Intra muscular needle insertion causes a particular pattern of afferent activity in peripheral nerves similar to what happens during physical exercise. Depending on the intensity, stimulation of the acupuncture needles activates muscle afferents to the spinal cord and the central nervous system ^[5]. The possible mechanisms of action in PCOS will be presented. Clearly, acupuncture affects PCOS symptoms via modulation of endogenous refulatory systems, including the sympathetic nervous system, the endocrine system and the neuroendocrine system ^[6,7].

We have conducted a study on women with well defined and diagnosed PCOS and anovulation to elucidate the effect of repeated electro-acupuncture (EA) treatments on endocrinological and neuroendocrinological parameters as well as on anovulation ^[8]. This study showed that repeated low frequency (2Hz) EA treatments exert long-lasting effects on both endocrinological parameters as well as anovulation. These results are in accordance with previous studies ^[9,10], but it is obvious that randomized, comparative studies are needed to verify the results. However, these studies do not enlighten possible underlying mechanisms of EA, but it can be hypothesized that these EA effects are mediated through inhibition of the activity in the ovarian sympathetic nerves.

In recent studies on an estradiol valerate (EV)-induced rat PCO model, we have showed that repeated low frequency EA treatments results in a reduction of high ovarian NGF ^[11], Corticotrophin releasing factor ^[12] and enothelin-1 concentrations ^[13], all markers for sympathetic activity, as well as increase low hypothalamic beta-endorphin concentrations and immune function ^[14]. Furthermore, low frequency EA increased ovarian blood flow indicating decreased ovarian sympathetic activity ^[13,15,16]. We have further tested the hypothesis that repeated low frequency EA treatments as well as physical exercise modulates sympathetic nerve activity in rats with steroid induced PCO by studying the expression of mRNA and protein of alpha_1a–alpha_1b–alpha_1d– and beta₂-adrenoceptors and the NGF receptor p75 ^NTR and immunohistochemical expression of TH ^[17,18]. Physical exercise almost normalized ovarian morphology and both EA and physical exercise normalize the expression of NGF and NGF-receptors, as well as alpha₁– and alpha₂-AR, suggesting that these interventions may have a therapeutical effect.
Recently, in female rats with PCOS induced by continuous prepubertal administration of dihydrotestosterone (DHT) ^[19], we found that both repeated low-frequency EA treatment and 4-5 weeks of voluntary exercise reduced insulin resistance ^[20]. This effect may involve regulation of adipose tissue metabolism and production since EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.
Further, we have shown that low-frequency EA and exercise downregulated mRNA expression of sympathetic markers compared with untreated PCOS rats. EA and exercise improved ovarian morphology, as reflected in a higher proportion of healthy antral follicles and a thinner theca interna cell layer than in controls. These findings support the theory that increased sympathetic activity contributes to the development and maintenance of PCOS and that the effects of EA and exercise may be mediated by modulation of sympathetic outflow to the adipose tissue and ovaries.

In conclusion, it appears that acupuncture may have beneficial effect on women with PCOS supported by both clinical and experimental evidence. However, there is a need for more RCTs on women wth PCOS well-defined diagnoses. The results indicate that low frequency EA modulates sympathetic activity.

(The work was supported in part by the Swedish Research Council (Project No. 2004-6399, and 2004-6827), LUA/ALF (Project No. 7092), Diabetic Foundation, Novo Nordisk, Ake Wiberg Research foundation, Ekhagastiftelsen, Wilhelm and Martina Lundgren’s Science Fund, Tore Nilssons Foundation, Hjalmar Svensson Foundation, and Magnus Bergwalls Stiftelse.)

References:

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