Original Article Pak J Med Res Vol. 50, No. 2, 2011

Demographic and Social Factors of Premature Ovarian Failure

Shaista Aziz Department of Gynaecology and Obstetrics, Baqai University Hospital, Karachi.

Abstract

Aims: To correlate the demographic and social factors associated with premature ovarian failure. Study type, settings and duration: Retrospective analysis of case records of patients attending the Gynaecology and Infertility Clinic of Baqai University Hospital, Nazimabad over 5 years. Patients and Methods: A total of 2500 patients were seen in the department over 5 years and out of these 45 had premature ovarian failure. Their age, parity, educational level, weight and information about sociodemographic characteristics, gynaecology and obstetrical data, general life style habits, history of other clinical conditions were recorded on a proforma report of results of hormones like Follicle Stimulating Hormone, Lutenising hormone, Estrogen, Progesterone, Thyroid hormones, Prolactin, Fasting serum Insulin and Antiphospholipid antibodies, Antiovarian antibodies and Thyroid microsomal antibodies measured by radioimmunoassay method were also recorded. The diagnosis of Premature Ovarian failure was made on serum follicle stimulating hormone level at 2 occasions few weeks. Results: Prevalence of Premature Ovarian Failure among infertility patients was 1.8%. Their mean age was 28 years at attaining amenorrhea. About 27(60%) had more than 12 years of education. Majority 40(88%) were nulliparous and 3(6.6%) had live births. Twenty seven (60%) patients gave the history of irregular cycles and secondary amenorrhea. Family history of premature ovarian failure was seen in 2(4.4%). Five (11%) patients showed fluctuating follicle stimulating hormone levels and 6(13%) had detected thyroid microsomal antibodies. Conclusions: Nulliparity, middle or high education level, life long irregular cycles and ovarian autoimmunity were associated with an increased risk of premature ovarian failure. Currently ovarian biopsy is the only way to diagnose it. Key words: Premature ovarian failure, risk factors, infertility, amenorrhea.

Introduction another study, statistically significant association between high education level and premature ovarian failure was remature ovarian failure is defined as elevated found but no association was found between premature 6 P gonadotrophins usually above 40 iu/l detected on ovarian failure, age at menarche and cycle length . two occasions (a few weeks apart), in a women before the Frequency of 17.1% of antiovarian antibodies were age of 40 years1. Patients may clinically present with observed in one study after laparoscopic ovarian drilling. primary or secondary amenorrhea. Other known causes of The presence of antiovarian antibodies is not associated 7 premature ovarian failure are chromosomal (12%), with poor ovarian reserve . familial (genetic) abnormalities2 (4-31%), and Patients of premature ovarian failure usually 8,9 autoimmune ovarian damage3,4 (14.3%), following pelvic present with subfertility . Estimation of ovarian reserve radiotherapy and chemotherapy and exposure to help in predicting her response in assisted conception and environmental factors like viral infections, heavy metals, in screening women for early ovarian ageing as a possible 10 solvents, pesticides, plastic industrial chemicals and cause for subfertility . Reproductive and life style factor cigarette smoke. have minor influences on the occurrence of premature One large cross sectional study showed that their ovarian failure. This suggest that genetic inheritance plays 4 is no significant association between risk of preterm a more important role . ovarian failure, education and age at menarche5. The same This paper describes an audit of patients study showed that life long irregular cycles and nulliparity presenting with premature ovarian failure attending the infertility clinic at Baqai University Hospital, Nazimabad. Corresponding Author: Shaista Aziz Patients and Methods Department of Gynaecology and Obstetrics Baqai University Hospital Karachi. Using hospital records, all patients coming to Email: [email protected] Gynaecology Clinic of Baqai University Hospital, ST ST are associated with risk of premature ovarian failure5. In Nazimabad from 1 January 2005 till 31 December

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2009 were reviewed, cases with infertility were sorted Thyroid microsomal antibodies were detected in 6(13%) from this number and finally those with ovarian failure while 9(20%) patients had high fasting serum insulin level were picked. Inclusion criteria were all the married more than 20 Uiu/ml (Table-2). Seventeen patient were women less than 40 years of age who had infertility and taking thyroxin, 22 metformin and 23 Aspirin. menstrual irregularity. Exclusion criteria were women One patient was hypertensive and 2(4.4%) were with age more than 40 years, presenting with lower diabetic. One patient was taking various antipsychotic abdominal pain, vaginal discharge and unmarried girls drugs following head injury in childhood and one patient and women who had conceived. had depression and was using antidepressants since 2 The case records of women with premature years, (information about dose and type of drugs was not ovarian failure were further studied including their age, available). parity, education level, height and weight. Information One patient was diagnosed as Wegener’s were also recorded on their sociodemographic granulomatosis and was on corticosteroids, characteristics, gynaecological and obstetric history, life cyclophosphamide and azathioprine therapy since 1 year styles and history of other medical and surgical problems, and she developed irregular cycles after treatment. Two and sign and symptoms. Serum gonadotrophins, fasting patients gave a family history of premature ovarian failure serum insulin and serum thyroid microsomal antibodies in their close relatives. were recorded. Five patients (11%) showed fluctuating follicle stimulating hormone levels of more than 40 iu/l which Results dropped down to near normal after few months and then again went up. A total of 10,550 patients visited the gynecology Five patients (11%) gave the history of previous department, out of whom 2500 patients had infertility and abdominal and pelvic surgery, out of which two had 45 cases had premature ovarian failure giving a laparotomy one had surgery for ruptured tubal ectopic, prevalence of 1.8% premature ovarian failure among the another for twisted gangrenous right ovarian cyst. infertility patients. Majority, 28(62%) of the cases were between 30-39 years of age and most of them presented Discussion with infertility after 4-8 years of marriage. There were 40(88%) nulliparous while 3(6.6%) each had previous In the present study, the prevalence of premature live births and repeated abortions. Majority of the ovarian failure was 1.8% in patient presenting at infertility patients had received more than 12 years of education. clinic. Nearly half of the patients had regular menstrual Twenty seven (60%) had normal body mass index only cycles. Over all 6(12%) cases conceived with 50% ending 2(4%) were underweight. About 14(31%) of patients had up in live deliveries while rest had abortion. oligomenorrhea and 8(18%) had secondary amenorrhea. Premature ovarian failure is a heterogeneous Mean age of onset of amenorrhea was 28 years (18-29) disorder which affects about 1% of women before the age (Table-1). of 40 years, 1 : 10,000 women below the age 20 and 1 : 1000 women below11 30. The most severe forms presents Table 1: Demographic and clinical characteristics of women with abnormal pubertal development and primary with premature ovarian failure. (N=45) amenorrhea, where as those with post pubertal onset are characterized by disappearance of menstrual cycle Age in <20 21-30 31-35 36-40 (secondary amenorrhea) associated with premature years 0 17(37.7%) 7(15.5%) 21(46.6%) follicular depletion.

Married 1-4 5-8 8-12 >12 In this study, secondary amenorrhea was found in years 8(18%) of the patients and this finding is consistent with 12 19(42.2%) 18(40%) 4(8.8%) 4(8.8%) other workers . Women with premature ovarian failure

Parity Nulliparous Multiparous have been reported to have poor obstetric outcome and 40(88.8%) 5(11.1%) fewer live births12.

BMI <20 20-24.9 25-29.9 >30 Only 6(12%) of the patients conceived and 2(4.4%) 27(60%) 13(28.8%) 3(6.6%) 3(50%) had live births and the rest had abortions. Menstural Regular Oligomeno Secondary Regulated Other studies have shown12 that 10-28% patients cycle -rrhoea amenorrhoea with pills presents with primary amenorrhea while in our study, none 8(40%) 14(31%) 8(17.7%) 5(11%) of the patients presented with primary amenorrhea. About 14(31%) patients in the study presented with irregular One third of the patients gave the history of hot cycles and this finding is conflicting with the other study13 flashes and complained of vaginal dryness and dysparunia.

Table 2: Hormones and antibodies levels of premature ovarian failure patients.

Pakistan Journal of Medical Research, 2011 (April - June) 72 Demographic and Social Factors of Premature Ovarian Failure

Hormones T3 T4 TSH FSI (Fasting serum insulin) Levels 0.6-2.5 ng/ml 4-12 ug/ml 0.6-6 Uiu/ml 1-9 10-20 >20 Not done No. of patients 17 17 17 24 0 9 9 <0.6ng/ml <4 ug/ml >6 Uin/ml

Hormones *FSH(1) *FSH(2) *FSH(3) LH Levels >40 U/l <40 U/l >40 U/l >40 U/l <40 U/l >40 U/l No. of patients 45 6 39 45 23 22

Thyroid microsomal antibody titre 1 : 40 1 : 80 >1 : 80 No. of patients 3 2 1

* Follicle stimulating hormone that suggested that irregular menstrual pattern may be twisted gangrenous right ovarian cyst thus showing the associated with late menopause6. This conflicting finding possibility of ovarian damage in these cases. suggests that irregular menstrual cycles occur due to Despite the heterogeneity of cause of premature impaired ovarian function and these women subsequently ovarian failure the fundamental treatment principals are developed premature ovarian failure. the same. Estrogen replacement and fertility options need Most of our patients belong to middle to be reassessed at intervals and clinicians have to be socioeconomic class and majority were educated. No vigilant for psychological sequelae18. relation was found in the body mass index and premature Premature ovarian failure is rare but does lead to ovarian failure which is in conflict with other study14. problems related to pregnancy and its loss19. Restoring Studies2,11 showed that in most cases, etiology ovarian function by proper immune modulation therapy is remains unknown and in our study 75% cases had the treatment option. Currently ovarian biopsy is the only unknown cause . way to diagnose autoimmune premature ovarian failure20. Autoimmunity is an associated factor for This study has limitations that being a premature ovarian failure and was seen in this study. retrospective study, it has no control group. In a few Although ovarian failure can also be caused by patients important information was missing. Therefore, a polyendocrinopathy due to adrenal and thyroid disease15,16, longitudinal study is suggested to come to solid but in our patients thyroid microsomal antibodies appear conclusions. to be the associated factor. Similar findings were reported 13 by other authors 20%. References Family history of premature ovarian failure is often found in these cases and in the present study 1. Chiristin-Maitre S, Pasquier M,Donadile B, Bouchard P. 2(4.4%) had a family history. This was also reported by Premature ovarian failure. Ann Endocrinol (Paris) others17 (4-31%). In families with premature ovarian 2006;67:557-66. failure the risk of other females developing premature 2. Beck-Peccoz P, Persani L. Premature ovarian failure ovarian failure depends upon the mode of inheritance and (review). Orphanet J Rare Dis 2006;1:9. transmission3. Therefore, females with family history of 3. Bachelot A, Rouxel A, Massin N, Dulon J, Courtillot C, ovarian failure may be advised to have children at an Matuchantsky C et al. Phenotypic and genetic studies of 357 consecutive patients presenting with premature early age. ovarian failure. Eur J Endocrinol 2009;161:179-87. Premature ovarian failure also occurs secondary 4. Belvis L, Bombelli F, Sironi L, Doldi N. Organ-specific to cytotoxic chemotherapy and this was seen in one of autoimmunity in patients with premature ovarian failure. J our patient who had Wegener’s Granulomatosis and she Endocrinol Invest 1993; 889-92. developed cycle irregularity following chemotherapy. 5. Progetto Menopause Italia study group. Premature ovarian The diagnosis of premature ovarian failure is made on failure: Frequency and risk factors among women serum follicle stimulating hormone level at 2 occasions attending a network of menopause clinic in Italy. BJOG few weeks apart1. The reason for two samples is the 2003;110:59-63. fluctuating levels of this hormone. Many women have 6. Testa G, Chiaffarino F,Vegetti W, Nicolosi A, Caliari I, Alagna F,Bolis PF,Parazzini F,Crosignani PG.Case – unpredictable course of relapse and remission and are control study on risk factors for premature ovarian failure. labeled as ‘Fluctuating ovarian function’ 5(11%) of our Gynecol Obstet Invest .2001;51: 40-3. patients fell into this category. 7. Emin A, Konova E, Lichev D, Alvazova N, Popov I. The Among the patients with fluctuating ovarian study of Ovarian autoimmunity and ovarian reserve in function 10-15% pregnancy rate has been reported13. women with uncertain sterility .Akush Ginekol Pelvic surgery has a potential to damage the (Sofilia)2008;479:20-3. ovary by affecting its blood supply or causing 8. Ghazi A, Sadique M, Siddiq N, Jabbar S, Ali T, Jaipal S. inflammation in the area13. In the present study, 2 patients Subfertility : Experience in a teaching care hospital. Pak J underwent laparotomy for ruptured tubal ectopic and Surg 2007;23:283-6.

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