Jul
5
PCOS: Acupuncture and Sympathetic Nerve Activity in Polycystic Ovary Syndrome
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Acupuncture PCOS
Elisabet Stener-Victorin1*, Elizabeth Jedel2, Per Olof Janson, and Yrsa Bergmann Sverrisdottir3
1 Institution of Neuroscience and Physiology
2 Osher Center for Integrative Medicine
3 inst. neuroscience and physiology
* To whom correspondence should be addressed. E-mail: elisabet.stener-victorin@neuro.gu.se.
Context: We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity. Animal studies support the concept that low-frequency electro-acupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. Objective: The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS. Design: Randomized controlled trial. Setting: Sahlgrenska University Hospital, Gothenburg, Sweden. Outcome Measures and Subjects: Twenty women with PCOS were randomly allocated to one of three groups; low-frequency EA (n=9), physical exercise (n=5) or to an untreated control (n=6) group during 16 weeks. Direct recordings of multiunit efferent postganglionic muscle sympathetic nerve activity (MSNA) in a muscle fascicle of the peroneal nerve before and following 16 weeks of treatment. Biometric, hemodynamic, endocrine and metabolic parameters were measured. Results: Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared to the untreated control group. Low-frequency EA group reduced sagittal diameter (P = 0.001), while physical exercise group reduced body weight (P = 0.004) and body mass index (BMI) (P = 0.004) as compared to the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for BMI and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine and metabolic variables. Conclusions: For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for women with PCOS.
Am J Physiol Regul Integr Comp Physiol (June 3, 2009). doi:10.1152/ajpregu.00197.2009
Feb
8
Acupuncture improves ovarian morphology in PCOS by regulating overactive sympathetic nervous system
Posted by admin in acupuncture, polycystic ovaries
Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS
Louise Mannerås,1 Stefan Cajander,2 Malin Lönn,3 and Elisabet Stener-Victorin1
1Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2 Department of Pathology and Cytology, Sunderby County Hospital, Luleå, Sweden; and 3 Institute of Medicine, Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Submitted 22 November 2008 ; accepted in final form 15 January 2009
Altered activity of the sympathetic nervous system, which innervates adipose and ovarian tissue, may play a role in polycystic ovary syndrome (PCOS). We hypothesize that electro-acupuncture (EA) and physical exercise reduce sympathetic activity by stimulating ergoreceptors and somatic afferent pathways in muscles. Here we investigated the effects of low-frequency EA and physical exercise on mRNA expression of sympathetic markers in adipose tissue and on ovarian morphology in female rats that received dihydrotestosterone (DHT) continuously, starting before puberty, to induce PCOS. At age 11 wk, rats with DHT-induced PCOS were randomly divided into three groups: PCOS, PCOS plus EA, and PCOS plus exercise. The latter two groups received 2-Hz EA (evoking muscle twitches) three times/week or had free access to a running wheel for 4–5 wk. In mesenteric adipose tissue, expression of ?3-adrenergic receptor (ADRB3), nerve growth factor (NGF), and neuropeptide Y (NPY) mRNA was higher in untreated PCOS rats than in controls. Low-frequency EA and exercise downregulated mRNA expression of NGF and NPY, and EA also downregulated expression of ADRB3, compared with untreated rats with DHT-induced PCOS. 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 untreated PCOS rats. 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.
sympathetic activity; ?3-adrenergic receptor; androgen receptor; nerve growth factor; neuropeptide Y
Sep
24
Acupuncture for male and female infertility – systematic review
Posted by admin in ART, IVF, acupuncture, female infertility, infertility, male infertility, polycystic ovaries
The Role of Acupuncture in the Management of Subfertility
Ng E H et al Fertil Steril. 2008 Jul;90(1):1-13.
Fertility and Sterility
Abstract
OBJECTIVE: To review systematically the use of acupuncture in the management of subfertility.
DESIGN: A computer search was performed via several English and Chinese databases to identify journals relevant to the subject.
RESULT(S): The positive effect of acupuncture in the treatment of subfertility may be related to the central sympathetic inhibition by the endorphin system, the change in uterine blood flow and motility, and stress reduction. Acupuncture may help restore ovulation in patients with polycystic ovary syndrome, although there are not enough randomized studies to validate this.
There is also no sufficient evidence supporting the role of acupuncture in male subfertility, as most of the studies are uncontrolled case reports or case series in which the sample sizes were small. Despite these deficiencies, acupuncture can be considered as an effective alternative for pain relief during oocyte retrieval in patients who cannot tolerate side effects of conscious sedation.
The pregnancy rate of IVF treatment is significantly increased, especially when acupuncture is administered on the day of embryo transfer.
CONCLUSION(S): Although acupuncture has gained increasing popularity in the management of subfertility, its effectiveness has remained controversial.
Mar
21
Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence.
Posted by admin in acupuncture, polycystic ovaries
pcos acupuncture
Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence.
Stener-Victorin E, Jedel E, Mannerås L.
Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. elisabet.stener-victorin@neuro.gu.se
Abstract
This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity. PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life. Despite extensive research, little is known about the aetiology of PCOS. The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation.
Feb
10
Systematic review: Acupuncture and IVF: Acupuncture improves rates of pregnancy and live birth
Posted by admin in ART, Chinese herbs, Chinese medicine, IVF, acupuncture, female infertility, infertility, male infertility, polycystic ovaries, stress/anxiety
Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis
Eric Manheimer, research associate1, Grant Zhang, assistant professor1, Laurence Udoff, assistant professor2, Aviad Haramati, professor3, Patricia Langenberg, professor and vice-chair4, Brian M Berman, professor1, Lex M Bouter, professor and vice chancellor (rector magnificus)5
1 Center for Integrative Medicine, University of Maryland School of Medicine, 2200 Kernan Drive, Kernan Hospital Mansion, Baltimore, MD 21207, USA, 2 Department of Obstetrics, Gynecology and Reproductive Services, University of Maryland School of Medicine, 3 Department of Physiology and Biophysics and Medicine, Georgetown University School of Medicine, Washington, DC, 4 Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 5 VU University Amsterdam De Boelelaan 1105, 1081 HV Amsterdam, the Netherlands
Correspondence to: E Manheimer emanheimer@compmed.umm.edu
Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation.
Design Systematic review and meta-analysis.
Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists.
Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients.
Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77).
Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.
Nov
16
Electro acupunture increases ovarian blod flow (PCOS)
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Effect of electro-acupuncture stimulation of different frequencies and intensities on ovarian blood flow in anaesthetized rats with steroid-induced polycystic ovaries
Elisabet Stener-Victorin1 ,2 , Rie Kobayashi3 , Orie Watanabe3 , Thomas Lundeberg4 and Mieko Kurosawa3
1Department of Physiology, Sahlgrenska Academy, Göteborg University, Box 432, SE-405 30 Göteborg, Sweden
2Department of Obstetrics and Gynecology, Sahlgrenska Academy, Göteborg University, Sahlgrenska University Hospital, Sahlgrenska, SE-413 45 Göteborg, Sweden
3Basic Medical Research Centre, International University of Health and Welfare, 2600-1 Kitakanemaru, Otawara, Tochigi 324-8501, Japan
4Department of Rehabilitation Medicine, Karolinska Hospital, SE-171 77 Stockholm, Sweden
Abstract
Background
Maintenance of ovarian blood flow (OBF) is suggested to be important for regular ovulation in women with polycystic ovaries (PCO). The purpose of the present study was to investigate whether electro-acupuncture (EA) of different frequencies and intensities can improve the OBF of anaesthetized rat in the animal model of PCO.
Methods
PCO was experimentally induced by a single intramuscular (i.m.) injection of estradiol valerate (EV) in rats. Control rats were given i.m. injection of oil. The involvement of the two ovarian sympathetic nerves; superior ovarian nerve (SON) and plexus ovarian nerve (OPN), in OBF responses was elucidated by severance of SON and OPN in both control and PCO rats. How systemic circulatory changes affect OBF was evaluated by continuous recording of the blood pressure. OBF was measured on the surface of the ovary-using laser Doppler flowmetry. Acupuncture needles were inserted bilaterally into the abdominal and hind limb muscles and connected to an electrical stimulator. Two frequencies – 2 Hz (low) and 80 Hz (high) – with three different intensities – 1.5, 3, and 6 mA – were applied for 35 s.
Results
Low-frequency EA at intensities of 3 and 6 mA elicited significant increases in OBF in the Control group compared to baseline. In the PCO group the increases in OBF were significant only when stimulating with low-frequency EA at 6 mA. After severance of the ovarian sympathetic nerves, the increased response of OBF that had been induced by low-frequency EA in both the Control and PCO group was abolished, indicating that the OBF response is mediated via the ovarian sympathetic nerves. High-frequency EA at 6 mA significantly decreased OBF and mean arterial blood pressure (MAP) in the Control group compared to baseline. In the PCO group, the same stimulation produced similar decreases in MAP, but not in OBF.
Conclusion
Low-frequency EA stimulation with a strong intensity (6 mA) increases OBF in rats with steroid-induced PCO whereas less strong intensity (3 mA) induces similar changes in control rats. Severance of the ovarian sympathetic nerves, abolish this OBF increase in both study groups, which suggests that the responses of OBF to EA are mediated via the ovarian sympathetic nerves.
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Sep
3
How acupuncture stimulates ovulation (the mechanism)
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Clinical studies on the mechanism for acupuncture stimulation of ovulation
Mo X; Li D; Pu Y; Xi G; Le X; Fu Z Zhejiang College of Traditional Chinese Medicine, Hangzhou.
Ovulatory dysfunction is commonly seen in gynecology clinic. It may cause infertility, amenia, functional uterine bleeding and a variety of complications. This research according to TCM theory records treating with acupuncture 34 patients suffering from ovulatory dysfunction. Changes in clinical symptoms and some relative targets are reported, plus findings in animal experiments. The theory concerning the generative and physiologic axis of women, this research involved the following points; Ganshu (UB 18), Shenshu (UB 23), Guanyuan (Ren 4), Zhongji (Ren 3), and Sanyinjiao (Sp 6). The reinforcement and reduction of acupuncture enables it to strengthen liver and kidney. Through the Chong and Ren channels it nourishes uterus to adjust the patient’s axis function and recover ovulation. Treated on an average of 30 times, the patients’ symptoms improved to varying degrees. The marked effective rate was 35.29%, the total effective rate being 82.35%. BBT, VS, CMS, and B ultrasonic picture all improved to some degree. The results also showed that acupuncture may adjust FSH, LH, and E2 in two directions and raise the progesterone level, bringing them to normal. The animal experiments confirmed this result. Results showed that acupuncture may adjust endocrine function of the generative and physiologic axis of women, thus stimulating ovulation. The results of this research will provide some scientific basis for treating and further studying this disorder.
Aug
1
In anovulatory infertility cases the hyperactive sympathetic system can be depressed by electro acupuncture and the function of the hypothalamus-pituitary-ovarian axis can be regulated by electro acupuncture via central sympathetic system
Posted by admin in acupuncture, female infertility, polycystic ovaries
Relationship Between Blood Radioimmunoreactive Beta-Endorphin and Hand Skin Temperature During The Electro-Acupuncture Induction of Ovulation
By Chen Bo Ying M.D. Lecturer of Neurobiology
Institute of Acupuncture Research, and Yu Jin, MD., Prof of Gynecology Obstetricus and Gynecology Hospital Shanghai Medical University Shanghai, People’s Republic of China
Abstract:
Thirteen cycles of anovulation menstruation in 11 cases were treated with Electro-Acupuncture (EA) ovulation induction. In 6 of these cycles which showed ovulation, the hand skin temperature (HST) of these patients was increased after EA treatment. In the other 7 cycles ovulation was not induced. There were no regular changes in HST of 5 normal subjects. The level of radioimmunoreactive beta-endorphin (rß-E) fluctuated, and returned to the preacupunctural level in 30 min. after withdrawal of needles in normal subjects. After EA, the level of blood rß-E in cycles with ovulation declined or maintained the range of normal subjects. But the level of blood rß-E and increase of HST after EA (r=-0.677, P <0.01). EA is able to regulate the function of the hypothalamic pituitary-ovarian axis. Since a good response is usually accompanied with the increase of HST, monitoring HST may provide a rough but simple method for prediciting the curative effect of EA. The role of rß-E in the mechanism of EA ovulation induction was discussed.
KEYWORDS: Electro-Acupuncture (EA), Hand Skin Temperature (HST), radioimmunoreactive beta-endorphin (rß-E), ovulation, radioimmunoassay (RIA).
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May
15
PCOS and Acupuncture: Electro-acupuncture normalises EV-induced changes in ovarian ARs
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Effect of electro-acupuncture on ovarian expression of alpha (1)- and beta (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries.
Manni L, Lundeberg T, Holmang A, Aloe L, Stener-Victorin E.
Cardiovascular Institute and Wallenberg Laboratory, Sahlgrenska Academy, Goteborg University, SE-413 45 Goteborg, Sweden. l.manni@in.rm.cnr.it
BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO. METHODS: In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of alpha1a-, alpha1b-, alpha1d-, and beta2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR). RESULTS: It was found that EV injection results in significantly higher mRNA expression of ovarian alpha1b- and alpha1d-AR in PCO rats compared to control rats. The p75NTR and beta2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of beta2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of alpha1a-, alpha1b- and alpha1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for alpha1b-AR. CONCLUSION: The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.
May
15
PCOS (polycystic ovaries): Acupuncture reverses PCOS NFG abdundance
Posted by admin in acupuncture, female infertility, polycystic ovaries
Electro-acupuncture reverses nerve growth factor abundance in experimental polycystic ovaries in the rat.
Bai YH, Lim SC, Song CH, Bae CS, Jin CS, Choi BC, Jang CH, Lee SH, Pak SC.
Research Division of Biological Science, Chosun University Medical School, Gwangju, Korea.
Polycystic ovary syndrome (PCOS) remains one of the most common causes of anovulation in women of reproductive age. There is some evidence that nerve growth factor (NGF) is involved in the pathogenesis of PCOS. Therefore, seeking the pathogenesis of PCOS is important for controlling fertility. In traditional Oriental Medicine, acupuncture has been used for the function of ovaries. The present study was designed to determine whether electro-acupuncture (EA) could affect experimentally induced polycystic ovary (PCO) in the rat. The two acupoints Sp-6 and E-128 were stimulated to test for efficacy in the protein expression of NGF. Polycystic ovaries were induced by a single injection of estradiol valerate (4 mg i.m.). During the experimental period of 8 weeks, some of the rats were treated with EA twice weekly; this group was compared with a vehicle-treated control group and an estradiol-injected group not subjected to EA. At day 60, the protein expression of NGF was examined by immunohistochemistry in the ovaries, the adrenal glands and some parts of the brain. The estradiol treatment induced a clear PCO appearance, and was associated with a robust increase in NGF expression in the ovaries, the adrenal glands and the brain. EA treatment partly reversed the NGF abundance, particularly in the ovaries, but not in the brain. Our data show that EA affects the NGF involvement in ovarian dysfunction. Copyright 2004 S. Karger AG, Basel
May
14
Acupuncture and PCOS anovulation: Electro-Acupuncture induces regular ovulations
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome.
Stener-Victorin E, Waldenstrom U, Tagnfors U, Lundeberg T, Lindstedt G, Janson PO.
Department of Obstetrics and Gynecology, Goteborg University, Sweden.
BACKGROUND: The present study was designed to evaluate if electro-acupuncture (EA) could affect oligo-/anovulation and related endocrine and neuroendocrine parameters in women with polycystic ovary syndrome (PCOS). METHODS: Twenty-four women (between the ages of 24 and 40 years) with PCOS and oligo-/amenorrhea were included in this non-randomized, longitudinal, prospective study. The study period was defined as the period extending from 3 months before the first EA treatment, to 3 months after the last EA treatment (10-14 treatments), in total 8-9 months. The menstrual and ovulation patterns were confirmed by recording of vaginal bleedings and by daily registrations of the basal body temperature (BBT). Blood samples were collected within a week before the first EA, within a week after the last EA and 3 months after EA. RESULTS: Nine women (38%) experienced a good effect. They displayed a mean of 0.66 ovulations/woman and month in the period during and after the EA period compared to a mean of 0.15 before the EA period (p=0.004). Before EA, women with a good effect had a significantly lower body-mass index (BMI) (p<0.001), waist-to-hip circumference ratio (WHR) (p=0.0058), serum testosterone concentration (p=0.0098), serum testosterone/sex hormone binding globulin (SHBG) ratio (p=0.011) and serum basal insulin concentration (p=0.0054), and a significantly higher concentration of serum SHBG (p=0.040) than did those women with no effect. CONCLUSION: Repeated EA treatments induce regular ovulations in more than one third of the women with PCOS. The group of women with good effect had a less androgenic hormonal profile before treatment and a less pronounced metabolic disturbance compared with the group with no effect. For this selected group EA offers an alternative to pharmacological ovulation induction.
May
12
Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis.
Chen BY.
Institute of Acupuncture, Shanghai Medical University, P.R. China.
This article summarizes the studies of the mechanism of electroacupuncture (EA) in the regulation of the abnormal function of hypothalamic-pituitary-ovarian axis (HPOA) in our laboratory. Clinical observation showed that EA with the effective acupoints could cure some anovulatory patients in a highly effective rate and the experimental results suggested that EA might regulate the dysfunction of HPOA in several ways, which means EA could influence some gene expression of brain, thereby, normalizing secretion of some hormones, such as GnRH, LH and E2. The effects of EA might possess a relative specificity on acupoints.
Acupunct Electrother Res. 1997;22(2):97-108.
May
11
Chinese medicine/herbs and PCOS
Posted by admin in Chinese medicine, female infertility, polycystic ovaries
Clinical observation on treatment of 43 women with polycystic ovary syndrome based on syndrome differentiation
[Article in Chinese]
Jia LN, Wang XJ.
Department of Gynecology of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
OBJECTIVE: To investigate the therapeutic effect of treatment based on syndrome differentiation and its influence on the serum levels of testosterone and insulin in women with polycystic ovary syndrome (PCOS). METHODS: Forty-three women, diagnosed with PCOS as well as syndrome of kidney yin deficiency or syndrome of spleen qi deficiency, were enrolled in the study. Twenty-five PCOS women with syndrome of kidney yin deficiency were treated with traditional Chinese herbs for nourishing yin to reduce fire (nourishing yin group), and 18 PCOS women with syndrome of spleen qi deficiency were treated with herbs for invigorating spleen and replenishing qi (replenishing qi group). Body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and the serum levels of insulin and testosterone before and after treatment were detected. RESULTS: Among the 43 cases, 20 cases had high serum testosterone level, in which 13 cases with syndrome of kidney yin deficiency, 7 cases with syndrome of spleen qi deficiency, but the difference had no statistic significance; 17 cases had high serum insulin level, in which 11 cases with syndrome of spleen qi deficiency, 6 cases with syndrome of kidney yin deficiency, the difference had statistic significance (P<0.05). In nourishing yin group, the serum levels of insulin and testosterone declined after treatment (P<0.05), and BMI, WHR and WC showed no significant changes. In replenishing qi group, the serum level of insulin declined after treatment (P<0.01), and BMI, WHR, WC and the serum level of testosterone showed no significant changes. CONCLUSION: Traditional Chinese herbs for nourishing yin to reduce fire can significantly reduce the serum levels of testosterone and insulin in PCOS women with syndrome of kidney yin deficiency, and herbs for invigorating spleen and replenishing qi can significantly reduce the serum level of insulin in PCOS women with syndrome of spleen qi deficiency.
Zhong Xi Yi Jie He Xue Bao. 2006 Nov;4(6):585-8.
Feb
26
Acupuncture and IVF embryo transfer, ART and PCOS
Posted by admin in ART, IVF, acupuncture, polycystic ovaries
Acupunct Med. 2006 Dec;24(4):157-63.
Use of acupuncture in female infertility and a summary of recent acupuncture studies related to embryo transfer.
Stener-Victorin E, Humaidan P.
Institute of Neuroscience and Physiolopgy, Sahlgrenska Academy, Goteborg University, Sweden. elisabet.stener-victorin@neuro.gu.se
During the last five years the use of acupuncture in female infertility as an adjuvant to conventional treatment in assisted reproductive technology (ART) has increased in popularity. The present paper briefly discusses clinical and experimental data on the effect of acupuncture on uterine and ovarian blood flow, as an analgesic method during ART, and on endocrine and metabolic disturbances such as polycystic ovary syndrome (PCOS). Further it gives a summary of recent studies evaluating the effect of acupuncture before and after embryo transfer on pregnancy outcome. Of the four published RCTs, three reveal significantly higher pregnancy rates in the acupuncture groups compared with the control groups. But the use of different study protocols makes it difficult to draw definitive conclusions. It seems, however, that acupuncture has a positive effect and no adverse effects on pregnancy outcome.
Jan
2
Effects of Electro-Acupuncture on Nerve Growth Factor and Ovarian Morphology in Rats with Experimentally Induced Polycystic Ovaries
Posted by admin in acupuncture, female infertility, infertility, polycystic ovaries
Effects of Electro-Acupuncture on Nerve Growth Factor and Ovarian Morphology in Rats with Experimentally Induced Polycystic Ovaries
1
Elisabet Stener-Victorin
2,a, Thomas Lundebergb, Urban Waldenströma, Luigi Mannic, Luigi Aloec, Stefan Gunnarssond, and Per Olof Jansona
a Department of Obstetrics and Gynecology, Göteborg University, SE-413 45 Göteborg, Sweden b Department of Physiology and Pharmacology, Karolinska Institutet, SE-164 01 Stockholm, Sweden c Institute of Neurobiology (CNR), Rome, Italy d Department of Evolutionary Biology, SE-752 36 Uppsala, Sweden
ABSTRACT
Despite extensive research on the pathogenesis of polycystic ovary syndrome (PCOS), there is still disagreement on the underlying mechanisms. The rat model for experimentally induced polycystic ovaries (PCO)—produced by a single injection of estradiol valerate—has similarities with human PCOS, and both are associated with hyperactivity in the sympathetic nervous system. Nerve growth factor (NGF) is known to serve as a neurotrophin for both the sympathetic and the sensory nervous systems and to enhance the activity of catecholaminergic and possibly other neuron types. Electro-acupuncture (EA) is known to reduce hyperactivity in the sympathetic nervous system. For these reasons, the model was used in the present study to investigate the effects of EA (12 treatments, approximately 25 min each, over 30 days) by analyzing NGF in the central nervous system and the endocrine organs, including the ovaries. The main findings in the present study were first, that significantly higher concentrations of NGF were found in the ovaries and the adrenal glands in the rats in the PCO model than in the control rats that were only injected with the vehicle (oil or NaCl). Second, that repeated EA treatments in PCO rats resulted in concentrations of NGF in the ovaries that were significantly lower than those in non-EA-treated PCO rats but were within a normal range that did not differ from those in the untreated oil and NaCl control groups. The results in the present study provide support for the theory that EA inhibits hyperactivity in the sympathetic nervous system.
adrenal, central nervous system, follicular development, hypothalamus, ovary, ovulation, pituitary, stress
INTRODUCTION
Polycystic ovary syndrome (PCOS), one of the most common causes of anovulation in women of reproductive age, is a complex endocrine and metabolic disorder [1]. Despite extensive research seeking the pathogenesis of PCOS, there is still disagreement on the underlying mechanisms. Different hypotheses of its pathophysiology have emerged, which indicates that the etiology is multifactorial and poorly understood.
Women with PCOS have an increased risk of endometrial cancer, hypertension, and type II diabetes, and they need some kind of long-standing treatment [2]. Traditional pharmacological treatment for ovulation induction is effective, but side effects such as superovulation are quite common. A previous clinical study on anovulatory women with PCOS showed that sensory stimulation (i.e., electro-acupuncture [EA]) affects endocrinological and neuroendocrinological parameters [3]. In addition, regular ovulations were induced in more than one-third of the women without negative side effects. These findings accord with previous reports [4–6] but do not enlighten underlying mechanisms. The mechanisms behind the beneficial effect of EA on PCOS in the human are difficult to study because tissue samples from the ovaries and the central nervous system (CNS) are for obvious reasons unobtainable. Studies on, for instance, neuropeptides in the gonads and the CNS would be possible to conduct in an animal model, provided that such a model exists.
Experiments on normal cycling rats have shown that exogenous estradiol valerate (EV), a long-acting estrogen, causes acyclicity and the formation of polycystic ovaries (PCO) [7, 8]. The changes include atretic antral follicles, follicular cysts with a well-developed theca cell layer, a diminished granulosa cell compartment, and luteinized cysts [7, 8]. Furthermore, the rats exhibited alterations in basal and pulsatile LH and FSH concentrations, changes in the pituitary response to GnRH, degenerative changes in the hypothalamus, altered opioid inhibitory tone on GnRH release, and high estradiol levels with a persistent pattern of constant estrus as assessed by vaginal smear [9, 10]. In addition, EV-induced PCO is associated with an increase in peripheral sympathetic outflow, evidenced by an increase in the release of norepinephrine (NE), an increase in ovarian NE content, and a decrease in the number of ß-adrenergic receptors in the ovarian compartments receiving catecholaminergic innervation [9–11]. Even if it is not possible to reproduce human PCOS using a rat model, it may provide important leads because a single injection of EV induces an anovulatory state that shares many endocrinological and morphological characteristics of human PCOS [7–13]. Thus, comparisons between the rat PCO model and human PCOS must be interpreted with caution because rat PCO ovaries contain multiple follicular cysts, the structure of which does not replicate the follicular growth arrest found in human PCOS. Contrary to previously held notions, the granulosa cells in the follicles accumulating in the human ovary are not atretic. However, both human PCOS and EV-induced PCO in rats may be associated with hyperactivity in the sympathetic nervous system.
According to one theory, elevated concentrations of neurotransmitters found in women with PCOS and anovulation may be associated with psychological stress and with hyperactivity in the sympathetic nervous system [3, 12, 13]. That superior ovarian nerve transection restores estrus cyclicity and ovulatory capacity in rats with EV-induced PCO further supports the theories of sympathetic hyperactivity [9]. Other evidence of neuronal involvement is that ovarian sympathetic innervation is under trophic control by nerve growth factor (NGF) [14]. This is also supported by the fact that the expression of the genes that encode NGF and one of its receptors, the low-affinity NGF-receptor, was dramatically increased in the ovary 30 days after EV injection [11]. Ovarian NGF is principally synthesized in the cells of the follicular wall [15], which is the site where the sympathetic neurons project to the ovaries [14]. The increase in the synthesis of NGF and its receptor that precedes the formation of cysts suggests that after PCO has been induced by EV injection, the neurons innervating the ovary are subjected to an enhanced neurotrophic influence that contributes to their hyperactivation and to the maintenance of an abnormally elevated catecholaminergic tone in ovarian steroid secretions [9–11].
Aim of the Study
Because NGF is known to serve as a neurotrophin for both the sympathetic and the sensory nervous systems and to enhance the activity of catecholaminergic and possibly other neuron types [9, 11, 14, 16–22], and because EA is known to reduce hyperactivity in the sympathetic nervous system [23–25], the experimentally induced PCO model was used to study the effects of EA by analyzing NGF in the CNS and the endocrine organs, including the ovaries.
The first part of the present study investigated dose-response—the discovery of the exact dose of EV needed to produce fully developed polycystic ovaries. The second part of this study investigated treatment with EA—what contribution NGF made to the etiology and maintenance of EV-induced PCO in rats and if and to what extent EA has an effect on NGF and ovarian morphology in experimentally induced PCO.
MATERIALS AND METHODS
Fifty-nine virgin adult cycling Sprague-Dawley rats (Möllegaard, Denmark) weighing 190–210 g and with regular 4-day estrous cycles were used. The rats were housed at 22°C, four to a cage, with free access to pelleted food and tap water and with a 12L:12D cycle for at least 1 wk before and throughout the experimental period. All rats received a single i.m. injection of either EV (Riedeldehaen, Germany), oil, or 0.15 M NaCl (Kabi Pharmacia AB, Sweden) and were anesthetized with enfluran (EFRANE, Abbott Scandinavia, Kista, Sweden) and killed by decapitation. The local Animal Ethics Committee at Göteborg University, Sweden approved the study.
Dose-Response
Twenty-seven rats were injected with one of two different doses of EV in an oil solution or with oil alone to ascertain the optimal dose for induction of PCO [8]. They were decapitated on three different occasions (15, 30, or 60 days after i.m. injection) to elucidate precisely when the ovaries display characteristic features of well-defined PCO [7, 8]. Nine rats received 2 mg EV in 0.2 ml oil/rat, nine rats 4 mg EV in 0.2 ml oil/rat, and nine rats 0.2 ml oil alone. Three rats per dose were killed on Day 15, three on Day 30, and three on Day 60.
Treatment with EA
The optimal dose (4 mg EV in 0.2 ml oil/rat) and timing (30 days after injection) were chosen for the experiments. In total, 32 rats took part. Eight rats in the EV control group and eight in the EA-treated EV group were injected i.m. with 4 mg EV in 0.2 ml oil/rat, eight rats in the oil control group with 0.2 ml oil, and eight rats in the NaCl control group with 0.2 ml 0.15 M NaCl. All 32 were decapitated on Day 30 after injection, that is, 1–2 days after the last EA treatment. All groups were anesthetized 12 times for about 25 min each time. Anesthesia was induced by inhalation of enfluran at 5.5–6.5 ml/h with an O2 and air flow of 0.25 L/min. The EA-treated EV group was subjected to 12 EA treatments every second or third day, beginning 2 days after the i.m. injection of EV. The stimulation points were bilateral in the quadriceps and erector spinae muscles at the level of thoracic (Th) 12 in the somatic segments according to the innervation of the ovaries (Th 12–lumbar [L]2, sacral [S]2–S4) (Fig. 1). The needles (Hegu; Hegu AB, Landsbro, Sweden) were inserted to depths of 0.5–0.8 cm and then bilaterally attached to an electrical stimulator (CEFAR ACU II, Cefar, Lund, Sweden) with a low burst frequency of 2 Hz. Individual pulses within the frequency were square wave pulses with alternating polarities and with a pulse duration of 0.2 msec, 80 pulses/sec. The intensity was adjusted so that local muscle contractions were seen to reflect the activation of muscle-nerve afferents (A-delta fibers and possibly C fibers) [26, 27]. The location and type of stimulation were the same in all rats.
Nerve Growth Factor Measurements by Enzyme Immunoassay
In the second part of the study, after the rats were decapitated, the pituitary gland, the hypothalamus, the hippocampus, one ovary, and the adrenal glands were quickly removed and dissected on dry ice, weighed, and stored at -80°C until extraction. The samples were sonicated in extraction buffer (0.1% Triton X-100, 100 mM Tris-HCl, pH 7.2, 400 mM NaCl, 4 mM EDTA, 0.2 mM PMSF, 0.2 mM benzethonium chloride, 2 mM benzamidine, 40 U/ml aprotinin, 0.05% sodium azide, 2% BSA, and 0.5% gelatin; 1 ml/100 mg of tissue), followed by centrifugation at 10 000 x g for 30 min. The supernatants were used for the assay. The bioactive form of 2.5S NGF purified from mouse submaxillary glands and prepared in the laboratory at the Institute of Neurobiology (CNR) in Rome, Italy, according to the method of Bocchini and Angeletti [28] was used as a standard. The NGF was dissolved in extraction buffer and the standard curve was in a range of 31.25 pg ml (-1) and 1 ng ml (-1). An ELISA was performed as described by Weskamp and Otten [29] with a minor modification [30]. Specific NGF binding was assessed by use of monoclonal mouse anti-ß-2.5S NGF (Boehringer Mannheim GmbH, Mannheim, Germany) that reacts with both the 2.5S and the 7S biologically active forms of NGF. The absorbency of samples and standards was corrected for nonspecific binding (i.e., the absorbency in a well coated with purified mouse IgG). The NGF content in the samples was determined in relation to the NGF standard curve. Data were not corrected for recovery of NGF from samples, which was routinely 70–90%, and was accepted only when the values were >2 SD above the blank. With these criteria, the limit of sensitivity of NGF ELISA averaged 0.5 pg per assay.
Morphology
One ovary per rat was removed, cleaned of adherent connective fat tissue, and fixed in 4% formaldehyde buffer; sections were stained with hematoxylin-eosin, and a trained pathologist performed a quantitative analysis of the follicle population. If ovum degeneration or at least one pyknotic granulosa cell was seen, the follicle populations were classified as atretic, otherwise they were classified as healthy. Morphological characteristics of follicular atresia were, for instance, scattered pyknotic nuclei in the granulosa cell layer [31], detachment of the granulosa cell layer from the basement membrane [32], fragmentation of the basal lamina [33], and the presence of cell debris in the antrum of the follicle [34].
Statistical Analyses
Statistical analyses were carried out using the SPSS 8.0 software. The NGF concentrations in the pituitary gland, the hypothalamus, the hippocampus, the ovary, and the adrenal glands were analyzed and the groups compared using ANOVA followed by multiple comparison procedures (Bonferroni test). All results are presented as mean ± SEM. A P value less than 0.05 was considered significant. The 95% confidence interval (CI) was given when P < 0.05.
RESULTS
Ovarian Morphology—Dose-Response
In the first part of the present study, dose-response, injection of 0.2 ml oil alone (control) was associated with a normal appearance of the ovaries and no differences were seen between rats sacrificed on Day 15, 30, or 60 (Fig. 2, a and b). No changes were seen in the ovaries of rats injected with 2 mg EV in 0.2 ml oil/rat and killed on Day 15. The ovaries of rats injected with the same dose of EV in oil exhibited small morphological changes resembling PCO when killed on Day 30 and 60 (Fig. 3, a and b). The ovaries of rats injected with a higher dose of EV (4 mg EV in 0.2 ml oil/rat) exhibited only small morphological changes on Day 15. Rats injected with the same dose of EV in oil and killed on Day 30 (Fig. 4, a–c) showed a progressive decrease in the number of primary and secondary follicles, but it was on Day 60 (Fig. 5, a and b) that the true cystic follicles appeared and the well-defined PCO was fully developed in accordance with previous reports by Brawer et al. [8].
FIG. 2.
a) Section of an ovary from a rat injected with 0.2 ml in oil and sacrificed on Day 30. In total, 11 corpora lutea (CL) marked with CL and three secondary follicles (SF) marked with SF are seen. One secondary follicle is framed (b). Magnification x2.5. Section stained with hematoxylin-eosin.
b) Normal secondary follicle. Magnification x20
FIG. 3. a) Section of an ovary from a rat injected with 2 mg EV in 0.2 ml oil and killed on Day 30. In total, six corpora lutea marked with CL and three atretic secondary follicles (ASF) marked with ASF are seen. The atretic secondary follicle is framed (b). Magnification x2.5: Section stained with hematoxylin-eosin. b) An atretic secondary follicle with granulosa cells showing signs of atresia and intact theca cells. Magnification x20
FIG. 4. a) Section of an ovary from a rat injected with 4 mg EV in 0.2 ml oil and sacrificed on Day 30. In total, seven corpora lutea marked with CL, three cystic follicles (CF) marked with CF, and two atretic secondary follicles marked with ASF are seen. One cystic follicle (b) and one atretic secondary follicle are framed (c). Magnification x2.5: Section stained with hematoxylin-eosin. b) Cystic degenerating follicle showing a thin granulosa layer and debris in follicular fluid. Magnification x20. c) An atretic secondary follicle with detachment of the oocyte from the cumulus mass of pyknotic granulosa cells. Magnification x20
FIG. 5. a) Section of an ovary from a rat injected with 4 mg EV in 0.2 ml oil and sacrificed on Day 60. In total, two corpora lutea marked with CL, five cystic follicles marked with CF and one secondary follicle marked with SF are seen. One cystic follicle is framed (b). Magnification x2.5. Section stained with hematoxylin-eosin. b) A cystic degenerating follicle showing a thin granulosa layer and debris in follicular fluid. Magnification x20
Ovarian Morphology—Treatment with EA
In the second part of the present study, treatment with EA, all rats were killed at Day 30 after EV injection, i.e., before the appearance of cystic follicles. The ovaries in the EV control group (4 mg EV in 0.2 ml oil/rat) displayed the same morphological changes as previously shown in the dose-response section (see Fig. 4, a–c). The ovaries in the oil control group and the NaCl control group exhibited a typically normal appearance (see Fig. 2, a and b). No substantial morphological differences were found between the EA-treated, EV group, and the EV control group.
Nerve Growth Factor—Treatment with EA
In the second part of the present study, treatment with EA, NGF measurements were made at Day 30 after EV injection. Means ± SEM for NGF (pg/g wet weight) in the hypothalamus, the pituitary gland, the hippocampus, the ovary, and the adrenal gland in all groups are presented in Table 1. Ovarian NGF concentrations were significantly higher in the EV control group compared to the oil control group (P < 0.001, CI = 178.7, 821.6) and the NaCl control group (P < 0.01, CI = 144.6, 787.5). The NGF concentrations in the ovary were significantly lower in the EA-treated, EV group compared to the EV control group (P < 0.05, CI = 6.2, 614.9) and did not differ from the oil and the NaCl control groups. The NGF concentrations in the adrenal glands were significantly higher in the EV control group and the EA-treated, EV group compared to both the oil control group (P < 0.001, CI = 45.7, 169.3 and P < 0.01, CI = 38.5, 166.5) and the NaCl control group (P < 0.001, CI = 21.9, 162.9 and P < 0.01, CI = 15.0, 159.8).
Weights of Ovaries and Adrenal Glands—Treatment with EA
Means ± SEM for weights (mg) of the ovaries and the adrenal glands in all groups are presented in Table 2. Ovarian weights in the control EV group and in the EA-treated, EV group were significantly lower compared to the oil control group (both P < 0.001) and the NaCl control group (both P < 0.001).
DISCUSSION
The main findings in the present study are as follows: First, PCO induced in rats by a single injection of EV results in significantly higher concentrations of NGF in the ovaries and the adrenal glands without any changes in the brain tissue when measured 30 days after EV injection. Second, repeated EA treatments with low frequency (2 Hz) significantly decrease the elevated NGF concentrations in the ovaries, to within a normal range, without affecting NGF concentrations in the adrenal glands or brain tissue when measured 30 days after EV injection.
The histological examination of the ovaries in the first part of the present study, dose-response, revealed that the optimal dose of EV that caused typical PCO-like morphological changes was 4 mg and that PCO was fully developed at Day 60. This dose was twice that used by Brawer and coworkers [7, 8] to achieve full development of a well-defined PCO in rats. The reason might be differences in the strain of rat and/or the estrogen preparation that was used. In addition, the ovarian weight in the two EV-injected groups was significantly lower compared to that in the vehicle-injected (oil and NaCl) control rats. The reduction in ovarian weight and size, as well, are in accordance with the findings of Brawer et al. [8]. The reduction in weight and size of the ovaries might be explained by a reduction in the number of corpora lutea. In the second part, treatment with EA, no substantial influence in ovarian morphology was seen at Day 30, after EV injection with the number and duration of the EA treatments used in this study. However, the main reason for beginning EA treatment as early as 2–3 days after EV injection and to decapitate at Day 30 after EV injection was to estimate whether EA could influence the increased ovarian NGF concentrations that have been shown to precede the development of morphological changes in rats with PCO [11]. It remains to be shown whether EA influences the ovarian morphology 60 days after EV injection. It would therefore be of interest to study the effects of EA after extended treatment periods. Such a study would provide a unique opportunity to collect experimental evidence of the effectiveness of EA in humans. In fact, we have observed that the multifollicular pattern characteristic of the ovarian morphology of women with PCOS and anovulation, as assessed by ultrasonography, began to disappear after they had received repeated EA treatments [3].
An involvement of the nervous system in the etiology and/or maintenance of PCOS is suggested by both clinical and experimental findings [9–13]. Clinical studies show that women with PCOS temporarily recover normal ovarian function after bilateral wedge resection or ovarian drilling that partially denervates the ovary [35, 36]. There is thus a possibility that the ovarian nerves are involved in the successful outcome of bilateral wedge resection and ovarian drilling.
Experimental observations in rats reveal that superior ovarian nerve transection in EV-induced PCO reduces the steroid response, increases ß-adrenoreceptor concentrations to more normal levels, and restores estrus cyclicity and ovulation [9]. These effects were linked to reduced activity in the ovarian sympathetic nerve fibers, indicating a peripheral neurogenic effect [9].
Sensory stimulation, i.e., EA, activates muscle-nerve afferents, mainly A-delta and possibly C fibers [23, 26, 27], that initiate a number of peripheral reactions at the spinal level and centrally in the brain. That EA may reduce hyperactivity in the ovarian peripheral sympathetic nerve fibers is in accordance with the theory that EA could modulate sensory, motor, and autonomic outflow at the segmental level [24]. In parallel, higher control systems are activated, resulting in the release of a number of neuropeptides, important in the modulation of central and segmental autonomic outflow, of the hypothalamic-pituitary-ovarian axis (HPO axis), and of the descending pain-inhibiting systems [23–25].
For obvious reasons it is not possible to subject control animals to true sham needle insertion. As soon as a needle penetrates the skin, it may be seen as a form of sensory stimulation that activates afferent nerve fibers. If a sham needle insertion without electrical stimulation is performed, then different acupuncture methods/stimulation techniques are being compared, and this does not provide proper information on the effect of EA versus no EA. We chose EA because the stimulation intensity is easy to standardize and it has been shown to be superior to manual needle stimulation [37]. In addition, to show a difference between two or more stimulation techniques would require a very large number of study subjects. In the present study, the control rats received the same enfluran anesthesia protocol as the rats treated with EA, which, in our opinion, is the best way to control completely environmental and/or emotional factors and the EA effect. The acupuncture needles in the present study were placed in the somatic segments that correspond to ovarian innervation. The needles were stimulated with low frequency EA for optimal activation of muscle-nerve afferents to inhibit the autonomic outflow at the segmental level and at the central level and to modulate the HPO axis. The choice of acupuncture points and the aim of stimulation has been the same as in our other EA studies on the female reproductive tract that dealt with blood flow in the uterine arteries prior to in vitro fertilization (IVF) [38], pain-relief during oocyte aspiration in connection with IVF treatment [39], and induction of ovulation in women with PCOS [3].
We have shown that repeated EA treatments restore regular ovulations in more than one-third of the anovulatory women with PCOS. In addition, EA-influenced neuroendocrine and endocrine parameters indicative of PCOS, such as LH/FSH ratios, mean testosterone concentrations, and ß-endorphin concentrations, decreased significantly [3]. The effects of repeated EA on anovulation were then attributed to an inhibition of hyperactivity in the sympathetic nervous system [3, 5, 6].
The findings of the present study support recent reports that ovarian NGF concentrations in rats with experimentally induced PCO [11] are elevated and that this increase can be related to a hyperactivity in the ovarian sympathetic nerves. Lara et al. [11] also suggests that activation of this neurotrophic-neurogenic regulatory loop is a component of the pathological process by which EV induces cyst formation and anovulation. They also stated that there is evidence that the alteration in neurotrophic input to the ovary contributes to the etiology and/or maintenance of human PCOS [11].
Furthermore, the present study shows that repeated EA treatments reduce peripheral sympathetic nerve hyperactivity, as revealed by the reduction in increased NGF concentrations in the ovaries into a normal range 30 days after EV injection, that did not differ from that of the untreated oil and NaCl control groups.
It remains to be shown whether EA directly affects sympathetic nerve activity. Measurements of the nervous output by analyses of the catecholamine release can resolve this. In addition, because receptors for NGF are expressed on the endocrine cells of the ovary, activities of ovarian NGF may mediate and/or be mediated by alterations in endocrine factors, for example, by corticotropin-releasing hormone, prolactin, oxytocin, and/or adrenal corticosteroid secretion. To resolve this, the same experimental protocol regarding EA and controls used here must be supplemented with measurements of serum levels of these hormones.
Whether this condition can be reversed with EA treatment at higher stimulation intensities, in higher numbers, and/or over longer periods remains to be shown.
The conclusion of this study is that repeated EA treatments reduce ovarian NGF concentrations to within normal ranges. This suggests that EA inhibits the hyperactivity in the ovarian sympathetic nerves, which may be of importance for the development and maintenance of experimentally induced PCO.
ACKNOWLEDGMENTS
The authors thank Professor Owe Lundgren and laboratory assistant Britt-Marie Fin, Department of Physiology, Göteborg University, for providing excellent working facilities and for invaluable laboratory help at their Department. We also thank Associate Professor Folke Knutsson for his invaluable assistance in the morphological analyses of the ovaries. Carl Löfman, M.D., Stockholm is acknowledged for skillful preparation of morphological specimens.
FOOTNOTES
First decision: 30 March 2000.
1 Supported by grants from the Hjalmar Svensson Foundation, Wilhelm och Martina Lundgrens Vetenskapsfond Wilhelm and Martina Lundgren’s Science Fund, and the Foundation for Acupuncture and Alternative Biological Treatment Methods.
2 Correspondence: Elisabet Stener-Victorin, Department of Obstetrics and Gynecology, Kvinnokliniken, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. FAX: 46 31829248;elisabet.stener-victorin@medstud.gu.se
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