CHAPTER 66 Polycystic Ovary Syndrome
Western medical perspective
Description
Originally described by Stein and Leventhal, polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. According to the initial description by Stein and Leventhal in 1935, the diagnosis of PCOS was based on the presentation of histologically verified polycystic ovaries together with the four clinical symptoms of:
In particular, the triad of amenorrhoea, hirsutism and obesity in the presence of polycystic ovaries was considered to be the essential feature of this disease.1
Nowadays it is widely recognized that PCOS is more than the classic Stein–Leventhal syndrome, as women with polycystic ovaries exhibit a wide spectrum of clinical presentations. Moreover, it is now apparent that the above triad of manifestations (amenorrhoea, hirsutism and obesity) together with bilateral polycystic ovaries is associated with a number of other endocrine disorders of diverse aetiology.2 These may include Cushing’s syndrome, congenital adrenal hyperplasia, ovarian hyperthecosis, hypothyroidism and chronic anovulation in association with hyperprolactinaemia.3
Alternatively, another expert conference held in Rotterdam in May 2003 defined PCOS, after the exclusion of related disorders, by two of the following three features:
In essence, the Rotterdam 2003 conference expanded the NIH 1990 definition, creating two new phenotypes:
PCOS often comes to light during puberty due to menstrual problems, which affect around 75% of those with the disease. Infrequent, irregular or absent periods are all common variations, many finding their periods particularly heavy when they do arrive. Indeed, a study of 100 women with PCOS found that case histories suggest endocrine aberrations occurring before puberty, prior to the final establishment of the hypothalamic–pituitary–ovarian system.5
The American Association of Clinical Endocrinologists lists the following facts about PCOS:
Endocrinology
Endocrinologically, PCOS is also heterogeneous; classically it is characterized by hyperandrogenism, inappropriate pituitary gonadotropin secretion (which causes an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio) and hyperinsulinism (see Fig. 66.1).
The degree of hirsutism associated with PCOS does not always correlate closely with the magnitude of androgen excess. Severe hirsutism may be associated with a slight elevation of androgens, while a substantial elevation of androgens may not always result in hirsutism.7
A major feature of PCOS is chronic anovulation with elevated levels of LH with low levels of FSH (Fig. 66.2). This abnormality in the LH and FSH is the result of a disruption in the feedback mechanism of the hypothalamic–pituitary–ovarian axis. The cyclical changes in ovarian oestrogen normally responsible for appropriate feedback regulation of cyclical gonadotropin release are overruled by a constant outpouring of oestrogen from extra-glandular sources. Thus, the secretion of excessive amounts of androgens and their subsequent conversion to oestrogen constitute the basis for the development of chronic anovulation in PCOS (Fig. 66.3).8
Yen summarizes the endocrinology of PCOS as follows:
The pathophysiology of chronic anovulation is not related to an inherent defect of the hypothalamic–pituitary–ovarian axis. Inappropriate gonadotrophin secretion with a high LH/FSH ratio is causally related to an elevated and relatively constant oestrogen feedback on the hypothalamic–pituitary–ovarian system. The LH-dependent hyperplasia of the theca cells and the associated hypersecretion of ovarian androgens are responsible for the high oestrogen levels through conversion of androgen to oestrogen by extra-ovarian tissues and inhibit sex-hormone binding globulin (SHBG) production. The low SHBG levels facilitate the rapid tissue uptake of free androgens for peripheral formation of oestrogen, and the increased adipose tissue provides excessive sites for androgen to oestrogen conversion. The high levels of oestrogen, in turn, augment pituitary sensitivity to luteinizing hormone-releasing hormone (LHRH) with the secretion favouring LH over FSH and results in self-perpetuating acyclicity with chronic anovulation.9
Patients with a history of anovulatory infertility and/or oligomenorrhoea or amenorrhoea and no evidence of recent corpora lutea were designated ‘anovulatory PCO’, and those ovaries from women reporting regular cycles which met the above morphological criteria, but in which a dominant follicle and/or a recent corpus luteum was observed, were designated ‘ovulatory PCO’. Normal morphology was assigned when the ovary was of normal size with soft, pliable stroma and contained not more than five follicles greater than 2 mm in diameter in a woman with regular menstrual cycles.10
Aetiology and pathology
The pathogenesis of PCOS is difficult to ascertain in view of the many subsets and different phenotypes of the syndrome. However, at least two major pathogenetic mechanisms are involved. First, there is an inherent defect in the regulation of gonadotropin secretion. Second, there is an altered regulation of folliculogenesis and/or ovarian steroid genesis. The latter may be related to hyperinsulinaemia, or auto/paracrine abnormalities of the ovaries which amplify the effects of LH in inducing ovarian hyperandrogenism: this further results in the formation of follicular atresia. Hyperandrogenaemia, in turn, perpetuates the inappropriate gonadotropin secretion, which promote a vicious cycle. The synergistic effect of obesity aggravating these mechanisms is important but obviously not primary.
The late consequences of PCOS, such as risk of endometrial cancer, cardiovascular disease and infertility, warrant an early and effective diagnosis of the syndrome.
The long-term risks of PCOS are related to both the insulin problem and the high androgen levels. High levels of insulin are associated with an increased risk of developing type 2 diabetes. Twenty-five to 35% of overweight PCOS women show signs of disruption of the insulin metabolism by their 30s and it probably becomes more common in the 40s and beyond.
The hormone changes described increase the chance of developing high blood pressure and high cholesterol levels, both of which can lead to a greater risk of heart disease.
Irregular or infrequent periods over a long period of time lead to an increased risk of endometrial cancer. This is in part due to high levels of oestrogen, which overstimulates the lining of the uterus. Absence of ovulation, and the resulting progesterone deficiency, also contributes to this risk.
Diagnosis
Ultrasound scan
This is usually done as an internal scan, i.e. a small ultrasound probe is placed just inside the vagina, giving the best view of the ovaries and pelvic organs. In PCOS, the ovaries are found to have multiple, small cysts around the edge of the ovary. These cysts are only a few millimetres in size, do not in themselves cause problems and are partially developed eggs that were not released (Plate 66.1). The cysts are usually lined with a few layers of granulosa cells and there is marked hyperplasia of the theca interna surrounding the many cystic follicles. It has been assumed that the hyperplastic theca cells are the result of chronic LH stimulation and the associated excessive androgen production.11
The marked hyperplasia of the theca interna surrounding the many cystic follicles in the ovaries of women with PCOS is a sign of Phlegm from the point of view of Chinese medicine.
The follicular cysts in the ovaries of women with PCOS do not mature fully and the absence of mature follicles results in low oestradiol production.
Blood tests
Two main blood tests will assist in making the diagnosis: one to check the level of androgens, such as testosterone, and another to measure the hormones involved in egg development. In PCOS there is a characteristic rise in LH. A progesterone blood test 7 days before the expected menstrual period can check if one is ovulating.
Although 60 years have passed since the first description of the syndrome, its definition and diagnostic criteria are still controversial. Several hormonal assays have been widely used to support the diagnosis, and are essential for exclusion of specific disorders which can cause polycystic ovaries. Accurate endocrine characterization of patients enables the recognition of biochemically more homogeneous subgroups of PCOS, which further provides facilities to better evaluate the pathogenesis of each of these subsets, and provides data necessary for formulating specific therapy.
Clinical manifestations
The main clinical manifestations of PCOS are as follows:
With regard to infertility, as PCOS is due to irregular or absent ovulation, it is a common cause of infertility. Not every woman with PCOS will be infertile as some will ovulate normally while some will ovulate less frequently (leading to a delay of pregnancy).
Difference between polycystic ovary and PCOS
The term ‘polycystic ovaries’ describes the ovaries, as seen on the ultrasound scan. Many women have ovaries that are polycystic, but do not have any of the other symptoms or hormone findings as described previously. Overall, around 20% of women of the general population have ovaries with this appearance, and what is not yet known from current research is whether this is one end of a long scale including the full polycystic ovary syndrome or a sign that symptoms are more likely to develop in the future.
Diabetes, insulin and PCOS
In recent years, it has become clear that PCOS is closely related to a problem with insulin metabolism. Insulin is a hormone released from the pancreas after a meal and it allows the organs of the body to take up energy in the form of glucose. In PCOS, there is a ‘resistance’ of cells in the body to insulin, so the pancreas makes more insulin to try and compensate. The excessively high levels of insulin have an effect on the ovary, preventing ovulation and causing a rise in androgen (testosterone) levels.
One study found that 30% of slim women with PCOS have insulin resistance, however it affects as many as 75% of those who are overweight. This explains why overweight women with PCOS are more likely to suffer with excessive hairiness and infertility related to not ovulating.
Risks associated with PCOS
Endometrial hyperplasia and endometrial cancer are risks associated with PCOS, due to over-accumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by oestrogen. It is however unclear if this risk is directly due to the syndrome or from the associated obesity, hyperinsulinaemia and hyperandrogenism.
Other risks associated with PCOS include:
Treatment
Periods may be controlled by the use of the contraceptive pill, which is most suitable for women under the age of 35 who also require contraception. The other type of drug used is a progesterone-like hormone. Progestagens are taken as tablets in a cyclical way, for example between days 12 and 26, the exact type and timing depending upon the woman’s individual cycle problem.
Some women have no periods at all, and either the contraceptive pill or cyclical progestagens are given to avoid the risk of endometrial cancer. From the Western perspective, around six periods per year are adequate to protect against the risk of endometrial cancer.
Infertility treatment
Polycystic ovary syndrome is found in around 70% of women who have ovulation difficulties leading to infertility. This is more common in women who are overweight, and as a first-line treatment, weight reduction can be very successful in restarting spontaneous ovulation. The amount that needs to be lost is small – around 5% of loss from the current weight is associated with an increased number of ovulatory cycles.
Ovarian stimulation
Clomifene citrate is the most commonly used drug to stimulate ovulation. It is taken in the early days of the cycle (usually days 2–6) and results in ovulation in around 80% of women overall, and a 6-month successful pregnancy rate of 45–50%.
When clomifene is unsuccessful, there are two main approaches. The first is to use injectable hormones to stimulate the ovary to produce eggs. This is known as ovarian stimulation and, where there is an additional sperm problem, is combined with insemination of sperm through the cervix around the time of ovulation (intra-uterine insemination, or IUI). The hormone treatment must be monitored by blood tests and ultrasound scans to avoid overstimulation. Live birth rates after ovarian stimulation following failed clomifene treatment reach 54% after 6 months and 62% after 12 cycles.
Multiple pregnancy is always a risk with this type of treatment, but especially so for women with PCOS whose ovaries are particularly sensitive to the hormones. If ovarian stimulation is unsuccessful, many women resort to in vitro fertilization (IVF), success rates of which depend very much upon individual characteristics such as age, length of infertility and weight.
Neither IVF nor ovarian stimulation is likely to be successful if a woman is overweight (body mass index greater than 30 kg/m2). This is why most hospitals restrict these treatments until a woman’s weight is within the normal range.
It should be noted that assisted-reproduction technology based on the use of ovarian stimulation is associated with an increased risk of multiple pregnancies, pregnancy complications, low birth weight, major birth defects and long-term disability among surviving infants.12
Laparoscopic ovarian diathermy
The alternative to ovarian stimulation is an operation called laparoscopic ovarian diathermy (LOD), also known as ‘ovarian drilling’. This involves a day case operation, a short general anaesthetic and a laparoscopy. The ovaries are identified and several small holes made in each ovary, either with a fine hot diathermy probe or via laser. It is not actually known how this works, but it can restore regular ovulation, or make the ovary more sensitive to clomifene.
By 12 months after LOD, the average pregnancy rate is around 60–80%, the greatest success rates being in women with a shorter length of infertility (less than 3 years) and a higher level of the hormone LH (>10 iu/l). Advantages of LOD include the fact that it may improve other symptoms of PCOS, such as menstrual disturbance, as well as avoiding the need for stimulatory drugs and their increased risk of overstimulation and multiple pregnancy.
Treatment of hirsutism
Hirsutism is usually due to above-average levels of androgens which are normally present in women at low levels. Initial treatments include bleaching and electrolysis. If these do not produce an acceptable result, drugs may be used to reduce the high androgen levels, if that is the cause.
The contraceptive pill contains oestrogen, which reduces androgen levels and will improve hirsutism. A formulation is available which includes a specific drug to reduce these further, known as Dianette®. Dianette® contains ethinyloestradiol and cyproterone acetate which is specific to treat the hirsutism. Cyproterone acetate is also used on its own at a higher dose than that contained in the Dianette® pill, but must be combined with adequate contraception, as it can cause fetal abnormality if taken during early pregnancy.
Spironolactone is another alternative, but this frequently causes erratic periods, so is often given with a low-dose contraceptive pill. A newer drug is called flutamide, an anti-androgen drug, but its safety profile has not been fully established. Side effects of the anti-androgens include tiredness, mood changes and reduced sex drive. Both flutamide and higher dose cyproterone acetate have the rare but serious side effect of causing problems with liver function, and so regular blood tests are advised.
All hirsutism treatments must be continued for 8–18 months before a response can be expected, due to the slow rate of hair growth.
Chinese medical perspective
In Chinese medicine, PCOS may correspond to several different gynecological diseases (Fig. 66.5):
This means that the pattern differentiation within each of the above Chinese disease-entities may be applied to the treatment of PCOS. In particular, the Chinese disease-entity that most closely corresponds to PCOS is ‘Infertility’. However, we cannot blindly apply the pattern differentiation of ‘Infertility’ (or other Chinese diseases) to PCOS without an understanding of the pathology of this disease from the Chinese perspective. The purpose of this chapter is precisely to discuss and interpret the Western pathology in terms of Chinese medicine. In other words, there is a huge difference between treating a woman suffering from unexplained infertility with a completely normal menstrual function and ovulation, and treating a woman with infertility deriving from PCOS.
Clinical manifestations
From a purely Chinese medicine perspective, i.e. ignoring hormonal changes and histological changes in the ovaries, the clinical manifestations are:
Amenorrhoea or scanty periods
Amenorrhoea or oligomenorrhoea indicate a deficiency of Blood of the Penetrating Vessel (Chong Mai) and a Kidney deficiency as they are the origin of Tian Gui. In some cases, amenorrhoea or scanty periods may also be due to Blood stasis within the Penetrating Vessel.
Hirsutism
Hirsutism is due to a dysfunction of the Penetrating Vessel with imbalance between Qi and Blood. A deficiency of Blood in the Uterus leads to amenorrhoea, but this would mean that there is more Blood available in the Penetrating Vessel at the skin level in the chin to promote the growth of hair. According to Chapter 65 of the Spiritual Axis, the Penetrating Vessel brings Qi and Blood to the chin area and, in women, losing some blood with menstruation, the Penetrating Vessel has relatively less Blood than Qi in this area compared to men. The lack of Blood in this area is the reason why women do not have a beard; as men have relatively more Blood in the head branch of the Penetrating Vessel, this Blood promotes the growth of hair on the face.13
Obesity
Obesity always indicates Damp-Phlegm. In the case of PCOS, it affects both the Penetrating Vessel and the Directing Vessel (Ren Mai). Zhu Dan Xi (1281–1358) mentions obesity as a sign of Phlegm and a factor in infertility in women in his book The Heart of Dan Xi’s Treatment Methods (Dan Xi Zhi Fa Xin Yao): “Inability to conceive in obese women is caused by the fat blocking the Uterus and leading to amenorrhoea: one must use herbs that resolve Phlegm”.14 This passage clearly equates obesity with Phlegm.
Ovarian cysts
Ovarian cysts are a typical form of ‘Abdominal Masses’ (Zheng Jia) from Phlegm. In the case of PCOS, they indicate Damp-Phlegm in the Penetrating and Directing Vessels.
Hormonal imbalance, raised testosterone
The deep hormonal imbalance of PCOS reflects from the Chinese point of view a dysfunction of the Governing Vessel (Du Mai), the Yang aspect of the menstrual cycle, and of the Penetrating and Directing Vessels.
Patterns
The main patterns appearing in PCOS are as follows:
The two most important patterns in PCOS are Damp-Phlegm in the Uterus and a Kidney deficiency. There is nearly always Damp-Phlegm in the Uterus which causes the ovarian cysts and the obesity and which contributes to the infertility by obstructing the Uterus and by interfering with hormone production by the ovaries.
Damp-Phlegm is the Manifestation (Biao). The main clinical manifestations of Damp-Phlegm in the Uterus are:
The second important pattern is Kidney deficiency, which may be of Yin or Yang but more often the latter. From the perspective of Chinese medicine, the deep hormonal imbalance points to a Kidney deficiency and an imbalance of the Governing, Directing and Penetrating Vessels (Du, Ren and Chong Mai). We could see the hyperandrogenism and the disruption of oestrogen metabolism of PCOS as a reflection of the imbalance between the Governing Vessel (controlling androgens in women) and the Directing Vessel (controlling oestrogen). If there is Blood stasis and/or Blood deficiency, then the Penetrating Vessel is also involved. The Kidney deficiency is therefore the Root (Ben) in PCOS.
Apart from the two fundamental patterns of Damp-Phlegm in the Uterus and Kidney deficiency, other possible patterns are:
Thus, the main patterns in PCOS are:
Comparison between PCOS and endometriosis
PCOS is a deeper, more difficult condition than endometriosis from the Chinese point of view. This is for various reasons:
Treatment of the extraordinary vessels and of phlegm
The following are examples of point combinations to open and regulate the Extraordinary Vessels in PCOS. Treatment of the Extraordinary Vessels is absolutely essential in the treatment of PCOS both to resolve Damp-Phlegm from the Uterus and to tonify the Kidneys (and therefore regulate hormones).
Directing Vessel (Ren Mai)
LU-7 Lieque (on the right) and KI-6 Zhaohai (left), Ren-4 Guanyuan, ST-28 Shuidao, Zigong. This treatment regulates the Directing Vessel, it tonifies the Kidneys and resolves Phlegm from the Uterus.
Penetrating Vessel (Chong Mai)
SP-4 Gongsun (right) and P-6 Neiguan (left), KI-14 Siman, SP-10 Xuehai, ST-28 Shuidao, LIV-3 Taichong. This treatment regulates the Penetrating Vessel, invigorates Blood and resolves Phlegm from the Uterus. I use the Penetrating Vessel more to invigorate Blood than to tonify the Kidneys (for which I use more the Directing Vessel).
Governing Vessel (Du Mai)
SI-3 Houxi (right) and BL-62 Shenmai (left), Ren-4 Guanyuan, Du-3 Yaoyangguan. This treatment regulates the Governing Vessel and tonifies Kidney-Yang.
Governing and Directing Vessel in combination
SI-3 Houxi (right), BL-62 Shenmai (left), LU-7 Lieque (left), KI-6 Zhaohai (right), Ren-4 Guanyuan, Du-20 Baihui, Du-3 Yaoyangguan. This treatment regulates the Governing and Directing Vessels and tonifies both Kidney-Yang and Kidney-Yin.
Besides treating the Extraordinary Vessels, in PCOS it is essential to resolve Damp-Phlegm from the Uterus. Herbal medicine resolves Dampness with herbs that are actual diuretics (Fu Ling Poria, Zhu Ling Polyporus, Yi Yi Ren Semen Coicis, etc.) and it resolves Phlegm with herbs that are drying (and therefore dry up Phlegm).
Acupuncture works in a different way and it can only resolve Dampness and Phlegm by regulating Qi in a way that it stimulates the movement, transformation and excretion of fluids. I feel that the Phlegm-resolving action of ST-40 Fenglong is overemphasized (and its many other functions underestimated).
One of the main functions of the Triple Burner is that of transforming, moving and excreting fluids. In order to affect the transformation, movement and excretion of fluids with acupuncture, it is necessary to mobilize all three Burners, albeit in differing proportions. For example, if the problem is in the Lower Burner, I would use quite a few points from the Lower Burner but also one or two from the Middle and Upper Burner.
The main points that regulate the fluid metabolism in each Burner are as follows:
Two sets of three points for each Burner stand out:
Interestingly, although the metabolism of fluids is a major function of the Triple Burner, the three Burners’ action on fluids has little to do with the Triple Burner channel: it is activated not so much by Triple Burner points (although T.B.-4 moves fluids) as by points of the Directing Vessel. The three main points have been indicated above but there are others such as Ren-6 Qihai, Ren-11 Jianli and Ren-3 Zhongji.
Thus, an example of point combination to resolve Damp-Phlegm in the Uterus in PCOS would be: ST-28 Shuidao, Ren-5 Shimen, BL-22 Sanjiaoshu, SP-6 Sanyinjiao, ST-40 Fenglong, KI-7 Fuliu (Lower Burner points), Ren-9 Shuifen (Middle Burner point) and LU-7 Lieque or Ren-17 Shanzhong (Upper Burner points). In addition to these points, in PCOS I would also regulate either the Directing or the Penetrating Vessel.
Identification of patterns and treatment
Damp-Phlegm in the Uterus
Clinical manifestations
Scanty periods, no periods, obesity, excessive hair, feeling of oppression of the chest, abdominal masses, excessive vaginal discharge. Tongue: Swollen with sticky coating. Pulse: Slippery.
Acupuncture
LU-7 Lieque on the right with KI-6 Zhaohai on the left, ST-28 Shuidao, Ren-9 Shuifen, Ren-3 Zhongji, SP-9 Yinlingquan, ST-40 Fenglong, BL-22 Sanjiaoshu. Reducing or even method on all points except LU-7 and KI-6 which should be needled with even method.
Herbal treatment
Women’s Treasure remedy
Clear the Palace is a variation of Qi Gong Wan Arousing the Uterus Pill to resolve Damp-Phlegm from the Uterus.
Damp-Phlegm in the Uterus
Clinical manifestations
Scanty periods, no periods, obesity, excessive hair, feeling of oppression of the chest, abdominal masses, excessive vaginal discharge. Tongue: Swollen with sticky coating. Pulse: Slippery.
Acupuncture
LU-7 Lieque (on the right) with KI-6 Zhaohai (on the left), ST-28 Shuidao, Ren-9 Shuifen, Ren-3 Zhongji, SP-9 Yinlingquan, ST-40 Fenglong, BL-22 Sanjiaoshu. Reducing or even method on all points except LU-7 and KI-6 which should be needled with even method.
Dampness or Damp-Heat
Clinical manifestations
Feeling of heaviness of the abdomen, mid-cycle pain and heaviness and/or bleeding, excessive vaginal discharge, acne, feeling of fullness of the abdomen, overweight. Tongue: sticky coating. Pulse: Slippery or Soggy.
Acupuncture
LU-7 Lieque (on the right) with KI-6 Zhaohai (on the left), SP-9 Yinlingquan, SP-6 Sanyinjiao, Ren-3 Zhongji, ST-28 Shuidao, Zigong, KI-14 Siman, BL-22 Sanjiaoshu, Ren-9 Shuifen, BL-32 Ciliao. Reducing or even method on all points except LU-7 and KI-6 which should be needled with even method.
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