Article PCOS in lesbian and heterosexual women treated with artificial donor insemination

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1 RBMOnline - Vol 17. No Reproductive BioMedicine Online; on web 22 July 2008 Article PCOS in lesbian and heterosexual women treated with artificial donor insemination Petra De Sutter is currently Head of the Infertility Clinic, and of the IVF and Research Laboratories of the Centre of Reproductive Medicine at the University Hospital in Gent, Belgium. She is also Professor in Reproductive Medicine at Gent University. Her fields of interest are clinical reproductive endocrinology and human embryology. Dr Petra De Sutter P De Sutter 1,3, T Dutré 1, F Vanden Meerschaut 1, I Stuyver 1, G Van Maele 2, M Dhont 1 1 Infertility Centre, University Hospital Ghent; 2 Department of Medical Informatics and Statistics, University Hospital Ghent 3 Correspondence: Tel: ; Fax: ; petra.desutter@ugent.be Abstract It has been claimed that the prevalence of polycystic ovary syndrome (PCOS) is significantly higher in lesbian compared with heterosexual women. The present study tried to corroborate this finding in a population of lesbian and heterosexual women consulting for artificial insemination with donor spermatozoa (AID) in the authors infertility centre. Separate Rotterdam criteria were compared, as well as the outcome of AID. Data were collected from patient files and 174 lesbian and 200 heterosexual women were included in this study. The diagnosis of PCOS was made following the Rotterdam PCOS consensus workshop group. A total of 8.0% of the lesbian women had PCOS compared with 8.7% of the heterosexual women. Concerning the presence of polycystic ovaries and cycle length and regularity, no significant differences were found. Conclusions about hirsutism and chemical hyperandrogenism were not made. Statistical analysis did not show any difference for the type and outcome of treatment. This study does not confirm a link between sexual orientation and the diagnosis of PCOS. The absence of a significant difference in therapy type and outcome emphasizes that there is no difference in (in)fertility rates between the study groups. Keywords: androgens, donor insemination, lesbian, PCOS, prevalence, sexual orientation Introduction 398 Polycystic ovary syndrome (PCOS) is an important pathology that occurs in 5 10% of the female population (Stankiewicz and Norman, 2006; Setji and Brown, 2007). This makes it the most common endocrinopathy in women and the most common cause of anovulation. The consequences of PCOS may be hirsutism, seborrhoea, acne, and androgenic alopecia, caused by high androgen levels (Carmina, 2006; Yildiz, 2006). It can be associated with oligo- or anovulation, which causes fertility problems (Gorry et al., 2006). The psychological consequences of having the syndrome should not be underestimated. The phenotype is visible for some patients and infertility can be hard for the patient to accept (Himelein and Thatcher, 2006; Barnard et al., 2007). All patients do not present with all symptoms, making the diagnosis of PCOS difficult. The Rotterdam ESHRE/ASRMsponsored PCOS Consensus Workshop Group (2004) selected the most important and consistent diagnostic criteria and accordingly PCOS is diagnosed when two of the following three criteria are present: typical transvaginal ultrasound picture of the ovaries; chemical and/or clinical hyperandrogenism; and oligo- or anovulation. However, these criteria have been criticized (Azziz et al., 2006; Franks, 2006; Geisthövel and Rabe, 2007). In 2004, Agrawal et al. described a higher prevalence of PCOS in lesbian than in heterosexual women. This study supports the old hypothesis that a lesbian sexual orientation may be associated with hyperandrogenism (Meyer-Bahlburg, 1979). Similarly, some authors have observed that girls born with congenital adrenal hyperplasia, who were subjected to increased androgen levels during fetal life, show more tomboy behaviour 2008 Published by Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB3 8DB, UK

2 in childhood and more often identify as homosexual women than controls (Money and Lewis, 1987; Hines et al., 2004), but others did not confirm this finding (Zucker et al., 1996). The finding of Agrawal et al. (2004) is important in view of the ongoing discussion of a possible association between sexual orientation and biological determinants (Bancroft, 1994; Gooren, 2006). The authors therefore decided to study the prevalence of PCOS in a large sample of lesbian and heterosexual women, treated with artificial insemination with donor semen in their centre. Because of the controversy about the Rotterdam criteria, they also compared separate diagnostic criteria. They also compared treatment types and outcomes as a marker for (in)fertility status in these women. Materials and methods Subjects Approval from the Ethics Committee of the University Hospital Ghent was obtained for this study. All subjects were subsequently recruited at the Infertility Centre from January 2002 until June A total of 374 women were included, of whom 174 were lesbian and 200 heterosexual. Patients were considered for inclusion when they consulted for artificial insemination with donor spermatozoa (AID). All patients presented with either a male or a female partner and their sexual orientation was assessed and confirmed following extensive psychological counselling, prior to acceptance for treatment. Single women were excluded, because sexual orientation was not only derived from what patients told, but mostly from the presence of a partner of the same or different gender. Patients in a transsexual relationship were excluded because of the sometimes ambiguous sexual orientation in these women, as well as patients whose files were not complete enough to enable the diagnosis according to the Rotterdam criteria. Data All data were collected retrospectively from patient files. The following parameters were evaluated: cycle pattern and length; basal LH, FSH, oestradiol and progesterone levels; clinical and/ or biochemical signs of hyperandrogenism; and basal ultrasound. Assessment of clinical acne and hirsutism was made on a +/++/+++ scale and in case of menstrual irregularity (cycles of >35 days), additional assessments were made for thyroxine-stimulating hormone, prolactin, cortisol, total and free testosterone, 17- OH-progesterone, androstenedione, dehydroepiandrosterone sulphate, and sex hormone binding globulin. Ultrasound was performed with a 5-MHz transvaginal transducer (Medison Sonoace 128 B and W, Benetec, Belgium) and images were obtained on day 2 or 3 of the menstrual cycle. All patients were seen by two experienced clinicians (PDS and MD), and all ultrasound images had been accurately described at the time of the consultation and were reviewed by one observer for the current study (PDS). For women who started AID treatment, cycle data were analysed until a first positive pregnancy test was reached or until drop-out. Every patient was entered only once in the study. Diagnosis of PCOS The diagnosis of PCOS was made by following the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) criteria strictly, including detailed ultrasound assessment as described in the consensus paper. Since not all three criteria could be scored for all women, analysis included separate diagnostic criteria as well. Because other diagnostic criteria are also used in the literature, the authors performed a secondary calculation using these criteria [National Institutes of Health (NIH), 1990 (see Zawadski and Dunaif, 1992) and Androgen Excess Society (AES), 2006 (see Azziz et al., 2006)]. The NIH 1990 criteria state that PCOS may be diagnosed if hyperandrogenism and/or hyperandrogenaemia is combined with oligo-ovulation (and other known disorders are excluded) (Zawadski and Dunaif, 1992). Following the AES 2006 criteria, PCOS may be diagnosed if clinical and/or biochemical hyperandrogenism is combined with ovulation dysfunction and/or polycystic ovaries (and exclusion of related disorders), also emphasizing the need for hyperandrogenism in order to diagnose PCOS (Azziz et al., 2006). Statistical analysis All data were put in a Statistics Package for Social Sciences (SPSS) 12 file (SPSS Inc., USA). For the comparison of means the Mann Whitney U-test was used. For the comparison of proportions the chi-squared test was used. A P value < 0.05 was seen as significant. Results The sexual orientation of the patients was deduced from their requesting fertility treatment either with a male or a female partner. All were Caucasian and had passed psychological screening consultations in order to be admitted to treatment with donor spermatozoa. The mean age for lesbian women was 30.6 years (range, years) and for heterosexual women 31.9 years (range, years). Lesbian women had a BMI of 24.6 ± 4.5 kg/m² and heterosexual women 25.1 ± 5.4 kg/m² (NS). Diagnosis of PCOS Table 1 shows the numbers of lesbian and heterosexual patients for whom the three Rotterdam criteria were fulfilled, not fulfilled or unavailable. Only if a diagnosis of PCOS could be made or ruled out with certainty were the patients included in the prevalence calculation. By using these criteria strictly, the authors found that 8.0% (12/150) of the lesbian women, compared with 8.7% (14/161) of the heterosexual women, had PCOS. This difference is not statistically significant. Analysis of the separate Rotterdam criteria Based on the analysis of available ultrasound images of the ovaries, 10.5% (17/162) of lesbian women, compared with 10.4% (18/173) of heterosexual women, had polycystic ovaries on pelvic ultrasound examination. This difference is not 399

3 Table 1. Cross table of presence (+), absence ( ) or unavailability (0) of individual diagnostic Rotterdam criteria for polycystic ovarian syndrome (PCOS) in lesbian (n = 174) and heterosexual women (n = 200). Lesbian women Heterosexual women First criterion: PCO ovaries Second criterion: menstrual cycle Third criterion: hyperandrogenism Criterion fulfilled; criterion not fulfilled; 0 criterion not available. Values in bold indicate certain diagnosis of PCOS; those in italic indicate certain diagnosis of no PCOS; those underlined indicate diagnosis not made. 400 statistically significant. Because data concerning clinical hyperandrogenism were lacking in many patient files and androgen levels were missing for all patients with regular menstrual cycles, this specific criterion was not analysed. The prevalence of oligo-amenorrhoea was not significantly different between the groups (20/174 or 11.5% for the lesbian women and 24/199 or 12.1% for the heterosexual women). Analysis using other diagnostic criteria (NIH 1990, AES 2006) If the NIH 1990 criteria (hyperandrogenism combined with cycle disorders, irrespective of ultrasound aspect of ovaries) are used, Table 1 shows that, from available data, the incidence of PCOS in lesbian women is 4/16 (25%) whereas in heterosexual women it is 8/27 (30%). From the patients in Table 1 for whom all necessary data were available to use the AES 2006 diagnostic criteria, it was calculated that in the group of lesbian women 4 of 16 were diagnosed with PCOS (25%) compared with 9 of 27 (33%) heterosexual women. AID treatment and outcome Of all the studied women consulting, 120 lesbians and 131 heterosexual women started AID. In both groups more than 60% of the women received no hormonal stimulation and were inseminated in a monitored normal menstrual cycle. About 25% of the women received clomiphene citrate and a minority received gonadotrophins (Figure 1). There was no statistical difference in the type of AID treatment between lesbian and heterosexual women, but the total number of AID cycles with hormonal stimulation was higher among the heterosexual women. The outcome of the AID treatment was also comparable between both groups. No statistically significant difference was found. More than half of the women had an ongoing pregnancy. On average both lesbian and heterosexual women became pregnant after three cycles of AID. Both groups of women stopped treatment on average after 6 7 cycles of AID. The prevalence of miscarriage and extrauterine pregnancy was similar to that in the general population (Figure 2). Discussion Although both groups in this study differed in age, this difference cannot be considered clinically significant; moreover, PCOS is not linked to a specific age group. A possible explanation for the fact that lesbian women in this study were slightly younger than heterosexual women, is that the former know from the start that they cannot conceive in a natural way. The age difference therefore reflects the waiting time of about 1 year for heterosexual couples before consulting a fertility centre. Furthermore, it is not thought that this age difference influenced the results. Body mass index (BMI) is an important factor in the aetiology of PCOS and could therefore be a confounder. However, there was no significant difference in BMI between both groups. This study suggests that there is no difference in the prevalence of PCOS in lesbian compared with heterosexual women consulting for AID. A possible association between sexual orientation and the prevalence of PCOS cannot be retained. This result is contradictory to the result of Agrawal et al. (2004), who reported that the prevalence of PCOS was significantly higher in a group of lesbian compared with heterosexual women. Moreover, they found much higher prevalences of PCOS than expected in the general population. In their study, 38% of lesbian women, compared with 14% of heterosexual women, had PCOS. It is generally accepted that the prevalence of PCOS in the general female population is 5 10%. The results obtained in the present study were 8.0% for lesbian women and 8.7% for the heterosexual group, corresponding perfectly to the commonly accepted prevalence figures. The fact that the

4 Figure 1. Type of treatment used for artificial insemination with donor spermatozoa Outcome of AID (%) Lesbian Unknown outcome Miscarriage Drop-out Biochemical pregnancy Hetrosexual woman Ongoing pregnancy Extra uterine pregnancy Figure 2. Outcome of treatment with artificial insemination with donor spermatozoa (AID) in lesbian and heterosexual women. prevalences in the Agrawal et al. (2004) study are much higher than expected, could be the result of the fact that these authors performed their study in a tertiary centre, well known for its clinical research on PCOS. Also, when the present authors recalculated the incidences in both groups using the NIH 1990 or AES 2006 criteria, they also obtain higher incidences (about 25 30%), indicating that incidence figures may vary significantly depending on the diagnostic criteria used. Even then, the present authors did not find a significant difference between both groups. In the present study, it was not possible to make a definite diagnosis according to the Rotterdam criteria for every woman. If only one criterion or two discordant criteria were available, a certain diagnosis was impossible and the patient was excluded from the analysis. This was the case for 24 lesbian and 39 heterosexual women. However, missing data were more likely to be found in the files of regularly menstruating women without clinical hyperandrogenism, and thus not having PCOS, than in women with cycle irregularities and/or clinical hyperandrogenism. In the latter patients, these data were always recorded. Women consulting for AID with or without ovulation induction were included. These women seek the help of an infertility centre because of a factor related to their partner (an infertile man or a female partner) and are not a priori subfertile themselves. Agrawal et al. (2004) included women who were all undergoing ovulation induction in combination with insemination. This may indicate that their population was primarily less fertile than the present one. However, it is not known if ovulation induction was done for medical indications or because it is a standard procedure in Agrawal et al. s centre. The prevalence of polycystic ovaries (PCO) was not significantly different between the groups in the present study. Lesbian women consulting for AID do not have a higher prevalence of PCO than heterosexual women consulting for AID. It is striking that the prevalence of PCO (10.5% of lesbian women compared with 10.4% of heterosexual women) is lower than the accepted general prevalence of PCO, which is 19% (Balen et al., 2005). This cannot be explained by a lack of data because in 90% of the cases good ultrasound images of both ovaries were available. However, in the present study imaging was not performed in real time but on pictures. Another possible explanation is that the ultrasound images were scored blindly, very strictly according to the Rotterdam criteria, and all by the same investigator. Moreover, there are no data in the literature concerning the prevalence of PCO for a Flemish population of women. In former studies, hypotheses were made about lesbianism being linked with raised concentrations of serum androgens (Gartrell et al., 1977). However, a consensus about this was never reached (Downey et al., 1987) and in contradiction with the Agrawal et al. (2004) findings, the present research supports 401

5 402 no theories that link lesbianism to PCO and/or PCOS. A limitation to the present study, however, is that only the lesbian women with the desire for a child and not their partners were studied. According to certain authors a lesbian couple may consist of two different types of women: butch-types (butches) and femme-types (femmes). The woman whom one defines as butch-type has more male characteristics and according to some authors also has raised androgen levels (Pearcey et al., 1996). However, recent studies have criticized this categorization as a binary construct (Luzzatto and Gvion, 2004). Moreover, Pearcey et al. (1996) found that within couples, individuals with higher butch ratings had significantly higher testosterone levels, but across all individuals as a whole (ignoring couple pairing) there was no correlation between testosterone and butch/femme ratings. Since in this binary construct the femme-type is expected to wish to carry the child, this type of woman in particular was represented in the present study. It may be that these women have lower androgen levels than their partners and therefore also less chance of being diagnosed with PCOS (Singh et al., 1999). Agrawal et al. (2004) included 10% of partners (possibly butch-type lesbian women) in their study, and it could be that this partly explains the higher prevalence figures for PCO and PCOS in their lesbian group. However, these authors observed no difference between both groups of lesbian women. The partners had no higher androgen levels and no higher prevalence of PCOS than the lesbian women who desired a child (possibly more feminine women). Study of the prevalence of PCOS in the partners of the present lesbian patients may shed more light on this question and is subject to ongoing research on this topic. In conclusion, this study has shown similar prevalences of PCOS and separate diagnostic criteria according to the Rotterdam consensus, between lesbian and heterosexual women treated with AID, as well as similar types of treatment and outcome. No association was found between the prevalence of PCOS and a lesbian sexual orientation. Acknowledgements PDS is holder of a fundamental clinical research mandate of the Flemish Foundation for Scientific Research (FWO-Vlaanderen). References Agrawal R, Sharma S, Bekir J et al Prevalence of polycystic ovaries and polycystic ovary syndrome in lesbian women compared with heterosexual women. Fertility and Sterility 82, Azziz R, Carmina E, Dewailly D et al Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. Journal of Clinical Endocrinology and Metabolism 91, Balen AH, Conway GS, Homburg R et al Polycystic Ovary Syndrome. 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