European Journal of Obstetrics & Gynecology and Reproductive Biology 183 (2014) 44–47
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Increased incidence of pelvic organ prolapse in women with acromegaly Ozlem Celik a, Suleyman Engin Akhan b, Esra Hatipoglu a, Pinar Kadioglu a,* a b
Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey Department of Gynecology and Obstetrics, Istanbul Medical School, University of Istanbul, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 July 2014 Received in revised form 22 September 2014 Accepted 4 October 2014
Objective: To evaluate gynecological problems of female patients with acromegaly and the relationship of these problems with the activity of the disease. Study design: Thirty-four women with acromegaly and 27 age- and body mass index-matched female healthy controls (HC) were included in the study. Demographic features, medical history, hormonal status and disease activity were obtained. A detailed gynecological examination was performed. Results: The incidence of pelvic organ prolapse (POP) was higher in patients with acromegaly (53%, n = 18) compared to the HC (15%, n = 4) (p = 0.003). Limiting the analysis to only cases with previous pregnancy, POP was seen in 18 (60%) of 30 cases with acromegaly and in 4 (20%) of 20 of the HC (p = 0.005). Additionally, in cases with prior vaginal delivery, POP was present in 18 (60%) of 30 cases with acromegaly and in 4 (24%) of 17 of the HC (p = 0.02). The frequency of POP was similar in patients with controlled and uncontrolled acromegaly (p = 0.3). Conclusion: Acromegaly may facilitate occurrence of pelvic organ prolapse and may cause additional health issues in female cases. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Acromegaly Fertility Gynecological problems Pregnancy Pelvic organ prolapse
Introduction Acromegaly is a state of excessive GH secretion, usually caused by a benign pituitary adenoma. In addition to its endocrine and metabolic consequences, it also has effects on various organs and tissues [1–4]. Previous reports have concluded that GH and IGF-1 receptors are widely expressed in many cells, including the gonads and genitalia [5–8]. It is therefore plausible that excessive GH or IGF-1 may also affect pelvic organs and may cause gynecologic problems in female patients with acromegaly. Because acromegaly is a rare disease with an insidious onset and usually diagnosed at midlife, few data are available on the frequency and causes of gynecological problems. The aim of this study was to evaluate gynecological problems of female patients with acromegaly and the relationship of these problems with disease activity. Methods A total of 34 women with acromegaly (controlled/uncontrolled:14/20), who were followed up and treated at the
* Corresponding author. Tel.: +90 5324041040; fax: +90 212 2333806. E-mail address: [email protected] (P. Kadioglu). http://dx.doi.org/10.1016/j.ejogrb.2014.10.009 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Cerrahpasa Medical School Endocrinology and Metabolism Outpatient Clinic between 1990 and 2013, were included in the study. A total of 27 age- and body mass index (BMI)-matched healthy female subjects without a chronic or endocrine disease comprised the healthy controls (HC). Demographic characteristics and medical history were obtained from all subjects. Cases who had had radiotherapy (RT) for control of acromegaly were asked about the order in which RT and pregnancy occurred. Fourteen cases with acromegaly (controlled: 8, uncontrolled: 6) and 10 of the HC had entered the menopause. A detailed gynecological examination was performed by the same gynecologist (S.E.A). Controlled disease activity was determined by the presence of clinical findings and failure to suppress the nadir GH level to less than 1 ng/mL during an oral glucose tolerance test (OGTT) and as well as high levels of IGF-1 adjusted for age and gender [9]. All the parameters were evaluated according to disease activity and compared to HC. Blood samples were taken to determine the levels of hormones before 10am in the early follicular phase in premenopausal and on any day in postmenopausal cases. A chemiluminescence immunoassay was done to assess PRL (normal: 3–23.3 ng/mL), LH (normal: 2.4–12.6 mIU/mL), FSH (normal: 3.6–12.5 mIU/mL), estradiol (normal: 12.5–166 pg/mL), DHEA-SO4 (normal: 96–340 mg/dL), total testosterone (normal: 0.05–0.82 ng/mL), cortisol (normal:
O. Celik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 183 (2014) 44–47
6.2–19.4 mg/dL), TSH (normal: 0.4–4.0 mIU/mL), and free thyroxine (normal: 0.8–1.9 ng/dL). A radioimmunoassay was done to assess free testosterone (normal: 0.45–3.17 pg/mL), 17-OH progesterone (normal: 0.15–1.3 ng/mL) and androstenedione (normal: 0.1–2.9 ng/mL). IGF-1 levels were evaluated after ethanol extraction with IRMA (Diagnostic System Laboratories Inc. Webster, Texas U.S.A.; normal values: 100–494 ng/mL for ages of 30–40 years, 101–303 ng/mL for ages of 40–50 years, and 78–258 ng/mL for ages of 50–70 years). Plasma GH levels were also studied with IRMA (GH; Immunotech, Marseille, France; normal value 2.5 were considered to have insulin resistance [10]. The study protocol was approved by the Ethics Committee of Cerrahpasa Medical School, Istanbul University. All the subjects read and signed the informed consent forms before enrolling in the study. The data were statistically analyzed using the SPSS 15.0 package program. The chi-square test was used for categorical variables. The Mann–Whitney U test was used to compare independent variables. Spearman’s correlation coefficient was used for the calculation of associations between variables. p < 0.05 was considered statistically significant. Results The mean age of the patients with acromegaly was 46.2 10.8 years and of the control group was 43.3 12.7 years (p = 0.3). The mean BMIs of patients with acromegaly and of the HC were 31.9 6.8 and 30.6 6.5 kg/m2, respectively (p = 0.5). There was no difference between the patients and the HC in terms of income level, smoking habits, menopausal status, and the time elapsed since entering menopause (p = 0.1, p = 0.7, p = 0.7 and p = 0.7, respectively). The acromegalic patients had lower levels of education, were more likely to be of rural origin, and had greater prevalence of Table 1 Demographic data of the female patients with acromegaly and healthy controls. Acromegaly (n, %)
Healthy controls (n, %)
0.01*
Origin Rural Urban
26 (76.5) 8 (23.5)
12 (44) 15 (56)
Educational level Low education (?8 years) High education (>8 years)
29 (85) 5 (15)
10 (37) 17 (63)
Income level ($/month)
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Increased incidence of pelvic organ prolapse in women with acromegaly Ozlem Celik a, Suleyman Engin Akhan b, Esra Hatipoglu a, Pinar Kadioglu a,* a b
Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical School, University of Istanbul, Istanbul, Turkey Department of Gynecology and Obstetrics, Istanbul Medical School, University of Istanbul, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 July 2014 Received in revised form 22 September 2014 Accepted 4 October 2014
Objective: To evaluate gynecological problems of female patients with acromegaly and the relationship of these problems with the activity of the disease. Study design: Thirty-four women with acromegaly and 27 age- and body mass index-matched female healthy controls (HC) were included in the study. Demographic features, medical history, hormonal status and disease activity were obtained. A detailed gynecological examination was performed. Results: The incidence of pelvic organ prolapse (POP) was higher in patients with acromegaly (53%, n = 18) compared to the HC (15%, n = 4) (p = 0.003). Limiting the analysis to only cases with previous pregnancy, POP was seen in 18 (60%) of 30 cases with acromegaly and in 4 (20%) of 20 of the HC (p = 0.005). Additionally, in cases with prior vaginal delivery, POP was present in 18 (60%) of 30 cases with acromegaly and in 4 (24%) of 17 of the HC (p = 0.02). The frequency of POP was similar in patients with controlled and uncontrolled acromegaly (p = 0.3). Conclusion: Acromegaly may facilitate occurrence of pelvic organ prolapse and may cause additional health issues in female cases. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Acromegaly Fertility Gynecological problems Pregnancy Pelvic organ prolapse
Introduction Acromegaly is a state of excessive GH secretion, usually caused by a benign pituitary adenoma. In addition to its endocrine and metabolic consequences, it also has effects on various organs and tissues [1–4]. Previous reports have concluded that GH and IGF-1 receptors are widely expressed in many cells, including the gonads and genitalia [5–8]. It is therefore plausible that excessive GH or IGF-1 may also affect pelvic organs and may cause gynecologic problems in female patients with acromegaly. Because acromegaly is a rare disease with an insidious onset and usually diagnosed at midlife, few data are available on the frequency and causes of gynecological problems. The aim of this study was to evaluate gynecological problems of female patients with acromegaly and the relationship of these problems with disease activity. Methods A total of 34 women with acromegaly (controlled/uncontrolled:14/20), who were followed up and treated at the
* Corresponding author. Tel.: +90 5324041040; fax: +90 212 2333806. E-mail address: [email protected] (P. Kadioglu). http://dx.doi.org/10.1016/j.ejogrb.2014.10.009 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Cerrahpasa Medical School Endocrinology and Metabolism Outpatient Clinic between 1990 and 2013, were included in the study. A total of 27 age- and body mass index (BMI)-matched healthy female subjects without a chronic or endocrine disease comprised the healthy controls (HC). Demographic characteristics and medical history were obtained from all subjects. Cases who had had radiotherapy (RT) for control of acromegaly were asked about the order in which RT and pregnancy occurred. Fourteen cases with acromegaly (controlled: 8, uncontrolled: 6) and 10 of the HC had entered the menopause. A detailed gynecological examination was performed by the same gynecologist (S.E.A). Controlled disease activity was determined by the presence of clinical findings and failure to suppress the nadir GH level to less than 1 ng/mL during an oral glucose tolerance test (OGTT) and as well as high levels of IGF-1 adjusted for age and gender [9]. All the parameters were evaluated according to disease activity and compared to HC. Blood samples were taken to determine the levels of hormones before 10am in the early follicular phase in premenopausal and on any day in postmenopausal cases. A chemiluminescence immunoassay was done to assess PRL (normal: 3–23.3 ng/mL), LH (normal: 2.4–12.6 mIU/mL), FSH (normal: 3.6–12.5 mIU/mL), estradiol (normal: 12.5–166 pg/mL), DHEA-SO4 (normal: 96–340 mg/dL), total testosterone (normal: 0.05–0.82 ng/mL), cortisol (normal:
O. Celik et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 183 (2014) 44–47
6.2–19.4 mg/dL), TSH (normal: 0.4–4.0 mIU/mL), and free thyroxine (normal: 0.8–1.9 ng/dL). A radioimmunoassay was done to assess free testosterone (normal: 0.45–3.17 pg/mL), 17-OH progesterone (normal: 0.15–1.3 ng/mL) and androstenedione (normal: 0.1–2.9 ng/mL). IGF-1 levels were evaluated after ethanol extraction with IRMA (Diagnostic System Laboratories Inc. Webster, Texas U.S.A.; normal values: 100–494 ng/mL for ages of 30–40 years, 101–303 ng/mL for ages of 40–50 years, and 78–258 ng/mL for ages of 50–70 years). Plasma GH levels were also studied with IRMA (GH; Immunotech, Marseille, France; normal value 2.5 were considered to have insulin resistance [10]. The study protocol was approved by the Ethics Committee of Cerrahpasa Medical School, Istanbul University. All the subjects read and signed the informed consent forms before enrolling in the study. The data were statistically analyzed using the SPSS 15.0 package program. The chi-square test was used for categorical variables. The Mann–Whitney U test was used to compare independent variables. Spearman’s correlation coefficient was used for the calculation of associations between variables. p < 0.05 was considered statistically significant. Results The mean age of the patients with acromegaly was 46.2 10.8 years and of the control group was 43.3 12.7 years (p = 0.3). The mean BMIs of patients with acromegaly and of the HC were 31.9 6.8 and 30.6 6.5 kg/m2, respectively (p = 0.5). There was no difference between the patients and the HC in terms of income level, smoking habits, menopausal status, and the time elapsed since entering menopause (p = 0.1, p = 0.7, p = 0.7 and p = 0.7, respectively). The acromegalic patients had lower levels of education, were more likely to be of rural origin, and had greater prevalence of Table 1 Demographic data of the female patients with acromegaly and healthy controls. Acromegaly (n, %)
Healthy controls (n, %)
0.01*
Origin Rural Urban
26 (76.5) 8 (23.5)
12 (44) 15 (56)
Educational level Low education (?8 years) High education (>8 years)
29 (85) 5 (15)
10 (37) 17 (63)
Income level ($/month)
