Polycystic Ovary Syndrome Endocrine Disorder Biology Essay

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women pre-menopausal. (Speca, Napolitano and Tagliaferri, 2007; Balen, 1999). Various studies have been carried out to try and assess the prevalence of PCOS in the population and figures range from 17-22%, with 22% being the most common. (Hart, Hickey and Franks, 2004). There is no known cause of the syndrome and its pathogenesis varies from literature to literature, hence the lack of international definition. (Speca et al., 2007). Until 2004, the most recognised definition of PCOS came from the National Institutes of Health (NIH) 1990 criteria for PCOS, and this described that patients who had PCOS had to have: hyperandrogenism and/or hyperandrogenemia, oligoovulation, and the exclusion of any other related disorders. (Azziz, 2006). As these criteria did not include the diagnosis of polycystic ovaries using ultrasonography, it was thought to be controversial, therefore in 2003, a meeting between the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine produced new criteria for the definition of PCOS, which was called the Rotterdam 2003 Criteria. It had been clear for some time that PCOS had a wide range of symptoms and the new criteria is thought to encompass more variations of the syndrome. Patients diagnosed with the old NIH criteria would also meet the new Rotterdam 2003 criteria. (Azziz, 2006). Symptoms in PCOS can include oligoovulation, anovulation, signs of hyperandrogenism which can be hirsutism, acne, seborrhoea, alopecia and obesity, and polycystic ovaries. (Speca, 2007). The new definition would first exclude any other disorders that may present in a similar way to PCOS and then the patient would expect to have two out of three of the following features: oligoovulation or anovulation; clinical and/or biochemical signs of hyperandrogenism; or polycystic ovaries. (Rotterdam ESHRE/ASRM Sponsored PCOS Consensus Workshop Group, 2004).

Transvaginal (TVS) ultrasonography has long been the modality of choice to image the ovaries and uterus and allows a non invasive assessment of the area. In scanning for PCOS, the sonographer according to the Rotterdam 2003 Criteria should abide by the strict guidelines before making a diagnosis. The polycystic ovary should have 12 or more follicles present measuring 2-9mm in diameter or for at least one of the ovaries to have a volume of 10cm3. (Balen, Laven, Tan and Dewailly, 2003). The use of three dimensional (3D) ultrasound in this area has grown mainly due to the desire to boost success rates in IVF procedures. (Timor-Tritsch and Monteagudo, 2007). The interest in studying PCO and PCOS solely has increased over the last few years and various studies have been carried out describing the features of PCO on three dimensional ultrasound. Ovarian volume is more accurately measured in 3D ultrasonography as it is more reproducible. (Raine-Fenning, Campbell, Clewes, Kendall and Johnson, 2003). Figure 1, illustrates the difference in size of a normal ovary compared to one which is polycystic. The formula for measuring the ovarian volume is that of a prolate ellipsoid -

where: D1 = maximum longitudinal diameter

D2 = maximum anteroposterior diameter

D3 = maximum transverse diameter (Pascual et al., 2008)

(a) (b)

Figure 1 - (a) Three dimensional (3D) power Doppler ultrasonography histogram analysis in a polycystic ovary syndrome (PCOS) patient. (b) 3D power Doppler ultrasonography histogram in a normal patient (Pan, Wu, Cheng, Li and Chang, 2002).

The introduction of 3D power Doppler has enabled the total flow of blood to the ovaries to be measured rather than just individual blood vessels. The volumes are then analysed using Virtual Organ Computer-Aided Analysis (VOCAL) software which produces blood flow indices. (Pan et al., 2002). These indices are vascularisation index (VI) which is the degree of vascularity; volume flow rate (FI) the signal intensity; vascularisation flow index (VFI) an amalgamation of VI and FI; and mean greyness (MG) which measures the echogenicity of the tissue. (Lam, Johnson and Raine-Fenning, 2007). These measurements have shown the most differences in patients with PCOS and are a valid tool in the diagnosis of PCOS.

Kyei-Mensah, Tan, Zaide and Jacobs (1998) were among the first to use 3D ultrasonography in assessing patients with PCOS. In their study they measured stromal volume (total ovarian volume minus follicular volumes), ovarian and follicular volumes. Measurements were taken in the early follicular phase as many patients were due for treatment in the later follicular phase. The patients that showed PCO on ultrasound were divided into two groups - group 1 with PCO and group 2 with PCOS. Both the ovarian and stromal volumes were significantly higher than the control group (P<0.05) in both the PCO and PCOS groups - 15.8mls and 14.5mls (mean of PCO and PCOS groups) versus 9.6mls and 8.6mls respectively. The degree of hyperandrogenism was not assessed which in later studies have proved to be important. All the women in the study had complained of infertility previously and therefore were self-selected for the study. This takes away the credibility of the study as the results were predictable.

Dolz et al. (1999) conducted a study of 65 women with PCOS showing signs of oligoovulation, clinical evidence of acne, alopecia or hirsutism and elevated hormone levels. Patients had to present with one abnormal clinical feature and one abnormal hormone level to be included in the study. The control group had 25 women with a normal menstrual cycle, a BMI <25kg/m2 and no medical, gynaecological or hormonal abnormalities. Ovarian area, follicle count and size, stromal echogenicity and thickness and vascular flow by impedance indices were recorded between days 8-10 of the menstrual cycle. Increased ovarian area, stromal thickness and vascular impedance indices (P<0.001) were observed. Similar to Jarvela et al. (2002) scans were carried out in the late follicular phase which has been shown to alter results. (Balen et al., 2003). The methodology that Dolz et al. (1999) used was different to all the other studies and doesn't allow for comparison.

Jarvela et al. (2002) carried out a study involving 14 patients with PCO rather than PCOS who were commencing IVF treatment. Patients didn't meet either the NIH consensus 1990 or the Rotterdam Criteria 2003. Measurements were taken from days 8-16 of the menstrual cycle which prevents the results from being compared to other studies. Most other literature in this area, scans patients in the early follicular phase (between days 2-5). Scans were carried out later so that they could rule out any other pathology that would afterwards prevent the patients from having successful IVF treatment. Balen et al. (2003) states that if follicles are >10mm then the scan should be repeated when ovarian quiescence is occurring, which is likely to be during the early follicular phase. Larger follicles are more common later in the follicular phase and can give a false diagnosis of PCO. Jarvela et al. (2002) demonstrated no difference between normal and PCO in VI, FI, VFI and MG but a significant difference (P<0.001) was seen in ovarian volume between the two groups. The mean ovarian volume was 13.2cm3 for PCO and 8.5cm3 for the control group. Unfortunately due to a questionable methodology this study is limited and has weakened any arguments for successful diagnosis of PCOS with 3D ultrasound.

Pan et al. (2002) used 25 women to demonstrated PCO sonographically, who also had a history of oligoovulation or amenorrhea and showed evidence of hirsutism, acne alopecia or obesity. The patients for this study would have all been included in the more recent definition of PCOS in the Rotterdam Criteria 2003. 54 women were recruited as the control group who all had normal ovaries, regular menstrual cycles and were undertaking IVF for male or tubal factors. Both groups had a transvaginal scan carried out between days 2-3 of the menstrual cycle. The ovarian volume and vascular indices (measured using 3D power Doppler and VOCAL software) were calculated. The results showed an increased ovarian volume, VI, VFI and FI were found in the PCOS patients (P<0.05). The age and BMI between the 2 groups also showed a significant difference (P<0.05) demonstrating that these parameters for both groups weren't the same. All the women were starting IVF treatment and doubts may come within the control group as the patients may have other ovarian pathologies that skew the results. Even though results were encouraging they have to be regarded with caution as the groups were not controlled sufficiently.

Ng, Chan, Yeung and Ho (2005) saw the importance of BMI in PCOS patients and divided its 32 PCOS patients into 2 groups - one with normal weight and the other with overweight (BMI ≥25kg/m2) patients. PCOS patients met the Rotterdam Criteria 2003 but all seemed to have oligoovulation and polycystic ovaries - no mention of hyperandrogenism within this group of patients. This may have been because the study involved a Chinese population where the prevalence of hyperandrogenism is much lower than Caucasian women. (Lam, Raine-Fenning, Cheung and Haines, 2009). 107 fertile women were used in the control group who had regular menstrual cycles and evidence of spontaneous conception. A transvaginal scan was carried out between days 2 and 4 of the menstrual cycle. Ovarian and stromal volume, antral follicle counts (AFC) and vascular indices were measured. Increased ovarian volume and AFC were seen in the PCOS group (P<0.001). Normal weight PCOS women had much higher vascular indices (VI, FI and VFI) then the overweight PCOS women. This demonstrates that within PCOS there are a variety of subcategories were ovarian vascularity may differ. (Aleem and Predonic, 1996). These subcategories have to be considered when interpreting results and the future consideration of these subcategories may aid in the diagnosis of PCOS.

Lam et al. (2007) used 80 Caucasian women, 40 women had been diagnosed with PCOS using the Rotterdam Criteria 2003 and the other 40 were undergoing fertility treatment due to male factor or unexplained infertility and had no sonographic evidence of PCO. The degree of hirsutism and acne were measured on a 4 point scale - (0) no clinical evidence to (3) severe evidence on the PCOS patients. All patients had a transvaginal scan between days 3 and 5 of the menstrual cycle, to measure for ovarian and stromal volumes, AFC and vascular indices. A significant increase (P<0.001) is seen in AFC, ovarian and stromal volumes, VI, and VFI in the PCOS patients. Lam et al. (2007) considered different phenotypic manifestations of PCOS and divided the PCOS patients into subgroups. This showed differences (P<0.05) between the normal and obese PCOS patients and the normo-androgenic and hirsute PCOS patients demonstrating that MG, FI and VFI were higher in the normal weight patients which agrees with Ng et al. (2005). Hirsute PCOS patients also had increased stromal volume and FI compared to the normo-androgenic PCOS patients (P<0.05). Lam et al. (2007) complements this work with further study - Lam, Raine-Fenning, Cheung and Haines (2009) recruiting 80 Chinese women. A similar methodology was used in this study but only normal weight PCOS patients had an increased VI and VFI. This correlates with Ng et al. (2005) who also showed increased VI and VFI in normal weight PCOS women. Other results were similar within the two ethnic groups. In Lam et al. (2009) no significant differences were found within the non-hirsute and hirsute PCOS patients which contradicts Lam et al. (2007), this again demonstrates that the Chinese population have a lower prevalence of hyperandrogenism. (Lam et al., 2009). Both studies reveal the importance of the subgroups within the PCOS patient.

Pascual et al. (2008) scanned 83 women, 38 with PCOS as defined by the Rotterdam Criteria 2003 and 45 women with normal menstrual cycles and sonographic ovarian pattern. Within the PCOS group the Ferriman-Gallwey score was used for hirsutism. This scores hair growth, in nine different regions of the body, on a scale of 0 (no hair growth) to 4 (complete and heavy cover). Ultrasound examinations were carried out in the early follicular phase (days 3-5) with ovarian volume and the vascular indices measured. The PCOS group were significantly younger (P<0.001) than the control group revealing that the characteristics of the women were different and could skew the interpretation of the final results. Only ovarian volume showed an increase (P<0.001) in the PCOS women compared to the control group. These results correlate with Jarvela et al. (2002) although testing was done at different stages of the follicular phase. Even though BMI, ovulation and hirsutism measurements were taken, they were not taken into consideration when analysing the results making this study potentially incomplete. Mala, Ghosh and Tripathi (2009) used a similar methodology as Pascual et al. (2008) but used 25 PCOS patients and 25 fertile women for the control group. The same measurements were taken around the same time in the menstrual cycle (days 2-5). Results showed that there was an increased ovarian volume, VI and VFI (P<0.001) in PCOS patients. These results contradict Pascual et al. (2008) when no clear differences are demonstrated in their methodologies apart from Pascual et al. (2008) used a larger group of women. Mala et al. (2009) did not subgroup the PCOS patients either, which Lam et al. (2007) and Lam et al. (2009) had shown is of significant importance in interpreting results.

The results from Dolz et al. (1999) and Jarvela et al. (2002) show the need for scans to be performed early on in the follicular phase as stated by Balen et al. (2003). Jarvela et al. (2002) also used patients with PCO rather than PCOS which all the other patients in other studies had. Kyei-Mensah et al. (1998) did not measure vascular indices therefore excluding Kyei-Mensah et al. (1998), Dolz et al. (1999) and Jarvela et al. (2002) from the results, all other studies apart from Pascual et al. (2008) showed some form of increase in the vascular indices. Normal weight PCOS patients seem to increase VI and VFI, which accounts for obese patients having lower hormone levels and lack of hyperandrogenism (Dolz et al., 1999). This may explain why the studies involving Chinese patients all demonstrated significant differences in vascular indices, (Pan et al., 2002; Ng et al., 2005; Lam et al., 2009) due to Chinese women having a lower prevalence of hyperandrogenism. (Lam et al., 2009). Lam et al. (2007), Lam et al. (2009) and Ng et al. (2005) indicted a need for different phenotypic manifestations within PCOS. (A summary of the results from all the studies can be found in Appendix D).

All studies demonstrated an increase in ovarian volume in the PCOS patient which was to be expected. A polycystic ovary by definition is considered polycystic if <10cm3. (Balen et al., 2003). In conclusion these nine studies all provided interesting results but were difficult to compare due to dissimilar methodologies and different patient characteristics. Further larger scale studies need to be carried out to give definite parameters for vascular indices, which can include the assessment of BMI, ovulation and hirsutism on the PCOS patient in 3D ultrasound. This will "assist in defining the severity, progression or regression of the disease." (Mala et al., 2009, 38).