Transgenerational PCOS

Stimulated by Risal et al 2019.[1]

Yes, I am late to this party! Well, in my defence, there is no mention of ‘acup’ anywhere in the text of this paper, so it did not pop up in my searches back in December 2019 when it was published. By the way, ‘acup’ is a really useful set of letters if you want to search for any word related to acupuncture or acupressure, and you don’t get any false positives… there do not seem to be any words with this combination of letters that are not associated with the subject.

Last Wednesday was the BMAS Women’s Health Day. We have held this day every year since 2007, and it is led by Elisabet (Lisa) Stener-Victorin… a unique surname to search for in the literature as well by the way. Lisa has been a full professor at the Karolinska Institute in Stockholm for the last few years, having moved her lab from the University in Göteborg (Gothenburg in English). She is certainly one of the most prolific researchers within the acupuncture field in the West, and in terms of quality, she has only few peers globally. Unfortunately for us in the world of acupuncture, Lisa has developed a primary interest in polycystic ovarian syndrome, and hence she publishes some papers that do not appear on my searches, such as this one.

This paper just popped up on one of her slides in the section on PCOS, and I sat up and took notice. This was new research that I was not expecting to see – I attend these days every year, and I usually know all her new papers. She said she was pleased to get this one published, and briefly summarised the findings. It was not until later that I searched out the paper in Nature Medicine and saw that her research was highlighted on the front cover of the issue.

…the front cover of Nature Medicine

The paper includes research on women from Sweden (register-based cohort) and Chile (clinical case-controlled) with laboratory research on a PCOS model in mice. For the first time Lisa’s extended team have demonstrated that the effects of prenatal androgen exposure can result in PCOS-like features for three subsequent generations. They also found 4 genes with altered expression in the model that were abnormally expressed in the daughters of women with PCOS as well as in unrelated women with PCOS.

In case any of you are going to try to read this paper and want to skip to the colourful graphical display of results, F1 refers to the first-generation female offspring of the mother that was exposed to androgens before pregnancy. F2 and F3 are the subsequent two generations. You can imagine that studying four generations is only really practical in a species that reproduces in a short timeframe, so Lisa had to move from rats to mice to achieve this.

Why study 4 generations?

Well, in the pregnant F0 sits both F1 in person as well as the germ cells forF2, so only going to F3 allows the study of a future generation that has not been directly exposed to the raised androgens.

This is an impressive piece of research, and Lisa is a good friend of the BMAS, but why am I highlighting this in a blog devoted to acupuncture research?

I’m coming directly to that now…

In the last 20 years Lisa and her colleagues have published at least 35 papers on acupuncture and PCOS. I will just mention a few of them here.

First came the effects of electroacupuncture (EA) on ovulation in PCOS.[2–5] Next we saw Lisa’s research veer towards the hormonal and metabolic profile, and how this might be mitigated with EA.[3,6–12] On the way, she even managed to demonstrate reduction in high muscle sympathetic nerve activity through both EA and exercise, and this was done via direct nerve recordings in women with PCOS.[13]

The bottom line here is that EA seems to ameliorate a number of the abnormal physiological, hormonal and metabolic parameters in PCOS, and or laboratory models, including alterations in genetic expression.[6,7,11,14–17]

It seems only a matter of time before we see the team investigate whether or not the effects of acupuncture in the prenatal period might mitigate these long-term transgenerational changes. If this proves to be the case there could be a lot of work for the acupuncturists of the future, unless the devices industry gets in first with an anti-PCOS bioelectric implant!

a word of caution…

But a word of caution before you all leap to treat pregnant women with PCOS! The team have already tried applying EA in pregnant rats exposed to excess testosterone, and the outcomes were worse rather than better. There were no adverse effects on the rats exposed to EA without testosterone, but the combination resulted in higher blood pressure and reduced placental function leading to decreased fetal growth.

So that was a small hiccup, but it is always good to have some negative or unexpected results. Afterall outside observers get a little suspicious if all your research is positive.

Let me finish on a positive note. I want to express my sincere thanks and appreciation for the pioneering work of Lisa and her extended team and colleagues and congratulate them for this ground-breaking research. They thoroughly deserve their front cover in Nature Medicine.


1         Risal S, Pei Y, Lu H, et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat Med 2019;25:1894–904. doi:10.1038/s41591-019-0666-1

2         Stener-Victorin E, Waldenstrom U, Tagnfors U, et al. Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2000;79:180–8. doi:10.1034/j.1600-0412.2000.079003180.x

3         Jedel E, Labrie F, Odén A, et al. Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Metab 2011;300:E37–45. doi:10.1152/ajpendo.00495.2010

4         Johansson J, Redman L, Veldhuis PP, et al. Acupuncture for ovulation induction in polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Metab 2013;304:E934–43. doi:10.1152/ajpendo.00039.2013

5         Wu X-K, Stener-Victorin E, Kuang H-Y, et al. Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial. JAMA 2017;317:2502–14. doi:10.1001/jama.2017.7217

6         Mannerås L, Jonsdottir IH, Holmäng A, et al. 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. Endocrinology 2008;149:3559–68. doi:10.1210/en.2008-0053

7         Mannerås L, Cajander S, Lönn M, et al. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS. Am J Physiol Integr Comp Physiol 2009;296:R1124–31. doi:10.1152/ajpregu.90947.2008

8         Feng Y, Johansson J, Shao R, et al. Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture. PLoS One 2009;4:e6638. doi:10.1371/journal.pone.0006638

9         Johansson J, Feng Y, Shao R, et al. Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome. Am J Physiol Metab 2010;299:E551–9. doi:10.1152/ajpendo.00323.2010

10       Stener-Victorin E, Baghaei F, Holm G, et al. Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial. Fertil Steril 2012;97:501–8. doi:10.1016/j.fertnstert.2011.11.010

11       Maliqueo M, Benrick A, Alvi A, et al. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome. Mol Cell Endocrinol 2015;412:159–69. doi:10.1016/j.mce.2015.04.026

12       Stener-Victorin E, Maliqueo M, Soligo M, et al. Changes in HbA1c and circulating and adipose tissue androgen levels in overweight-obese women with polycystic ovary syndrome in response to electroacupuncture. Obes Sci Pract 2016;2:426–35. doi:10.1002/osp4.78

13       Stener-Victorin E, Jedel E, Janson PO, et al. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Integr Comp Physiol 2009;297:R387–95. doi:10.1152/ajpregu.00197.2009

14       Manni L, Lundeberg T, Holmäng A, et al. 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. Reprod Biol Endocrinol 2005;3:21. doi:10.1186/1477-7827-3-21

15       Johansson J, Mannerås-Holm L, Shao R, et al. Electrical vs Manual Acupuncture Stimulation in a Rat Model of Polycystic Ovary Syndrome: Different Effects on Muscle and Fat Tissue Insulin Signaling. PLoS One 2013;8:e54357. doi:10.1371/journal.pone.0054357

16       Kokosar M, Benrick A, Perfilyev A, et al. A Single Bout of Electroacupuncture Remodels Epigenetic and Transcriptional Changes in Adipose Tissue in Polycystic Ovary Syndrome. Sci Rep 2018;8:1878. doi:10.1038/s41598-017-17919-5

17       Benrick A, Pillon NJ, Nilsson E, et al. Electroacupuncture Mimics Exercise-Induced Changes in Skeletal Muscle Gene Expression in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2020;105:1–15. doi:10.1210/clinem/dgaa165

Declaration of interests MC