Combining Ancient Chinese Treatments with Modern Physiotherapy

Institute of Neuroscience and Physiology, Department of Physiology / Endocrinology, Box 434, SE-405 30 Goteborg, Sweden

BY ELISABET STENER-VICTORIN

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 alpha1a–alpha1b–alpha1d– 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:

  1. Semenova, I. Adrenergic innervation of the ovaries in Stein-Leventhal syndrome. Vestn Akad Med Nauk SSSR (Abstract in English)24, 58-62 (1969).
  2. Heider, U., Pedal, I. & Spanel-Borowski, K. Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries. Fertil Steril75, 1141-1147. (2001).
  3. Greiner, M., Paredes, A., Araya, V. & Lara, H.E. Role of stress and sympathetic innervation in the development of polycystic ovary syndrome. Endocrine28, 319-324 (2005).
  4. Balen, A. Surgical treatment of polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab20, 271-280 (2006).
  5. Kagitani, F., Uchida, S., Hotta, H. & Aikawa, Y. Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II, III and IV single afferent nerve fibers in the dorsal spinal roots. Jpn J Physiol 55, 149-155 (2005).
  6. Andersson, S. & Lundeberg, T. Acupuncture – from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses45, 271-281 (1995).
  7. Stener-Victorin, E., Wikland, M., Waldenstrom, U. & Lundeberg, T. Alternative treatments in reproductive medicine: much ado about nothing: Acupuncture – a method of treatment in reproductive medicine: lack of evidence of an effect does not equal evidence of the lack of an effect.  Reprod.17, 1942-1946 (2002).
  8. Stener-Victorin, E., et alEffects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 79, 180-188 (2000).
  9. Chen, B.Y. Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis. Acupunct Electother Res 22, 97-108 (1997).
  10. Gerhard, I. & Postneek, F. Auricular acupuncture in the treatment of female infertility. Gynecol Endocrinol6, 171-181 (1992).
  11. Stener-Victorin, E., et al.Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol Reprod63, 1497-1503 (2000).
  12. Stener-Victorin, E., Lundeberg, T., Waldenstrom, U., Bileviciute-Ljungar, I. & Janson, P.O. Effects of electro-acupuncture on corticotropin-releasing factor in rats with experimentally-induced polycystic ovaries. Neuropeptides35, 227-231 (2001).
  13. Stener-Victorin, E., et al.Steriod-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system. Reprod Biol Endocrinol 1, 33 (2003).
  14. Stener-Victorin, E. & Lindholm, C. Immunity and beta-endorphin concentrationsin hypothalamus and plasma in rats with steroid-induced polycystic ovaries: effect of low-frequency electroacupuncture. Biol Reprod70, 329-333 (2004).
  15. Stener-Victorin, E., Fujisawa, S. & Kurosawa, M. Ovarian blood flow responses to electroacupuncture stimulation depend on estrous cycle and on site and frequency of stimulation in anesthetized rats. J Appl Physiol101, 84-91 (2006).
  16. Stener-Victorin, E., Kobayashi, R. & Kurosawa, M. Ovarian blood flow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats. Autonomic Neuroscience: Basic and Clinical108, 50-56 (2003).
  17. Manni, L., et al.Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries. J Neuroendocrinol 17, 846-858 (2005).
  18. Manni, L., Lundeberg, T., Holmang, A., Aloe, L. & Stener-Victorin, E. Effect of electo-acupuncture on ovarian expression of alpha(1)- and beta(2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries. Reprod Biol Endocrinol3, 21 (2005).
  19. Manneras, L., et al.A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology 148, 3781-3791 (2007).
  20. Manneras, L., Jonsdottir, I.H., Holmang, A., Lonn, M. & Stener-Victorin, E. Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome. Endocrinology149, 3559-3568 (2008).

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