Human Reproduction vol.6 no.4 pp.544-549, 1991
Prevalence and genesis of endometriosis
Tahir A.Mahmood1 and Allan Templeton Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Cornhill Road, Aberdeen AB9 2ZD, UK 'To whom correspondence should be addressed at Forth Park Hospital, Kirkcaldy, Fife KY2 5RA, UK
A group of 1542 pre-menopausal Caucasian women were assessed prospectively to investigate the prevalence of endometriosis. The women were either having laparoscopy because of infertiilty (n = 654), undergoing laparoscopic sterilization (n = 598), having laparoscopy because of chronic abdominal and pelvic pain (n = 156) or undergoing abdominal hysterectomy for dysfunctional uterine bleeding (n = 134). Endometriosis was noted more frequently among women being investigated for infertility (21%) than among those undergoing sterilization (6%). Among those being investigated for chronic abdominal pain, the incidence of endometriosis was 15%, while among those undergoing abdominal hysterectomy, it was 25%. In all groups the total duration of combined pill usage was significantly higher in patients who had a normal pelvis compared to those with endometriosis. It is suggested that among susceptible women, both fertile and infertile, a prolonged period of regular spontaneous menstruation may play a causative role in the genesis of endometriosis. Key words: prevalence/endometriosis/fertile - infertile/genesis
Introduction Laparoscopy is now accepted as an integral part of infertility investigation and as a result, endometriosis is more frequently diagnosed in the infertile population. Its incidence varies from as low as 2 % to as high as 48 %, but the generally accepted range is 2 0 - 4 0 % . A review of the literature is presented in Table I. The prevalence of endometriosis among previously fertile women undergoing laparoscopic sterilization varies between 1 and 18% while one recent study reported an unusually high incidence of 43%. These studies are reviewed in Table II. The occurrence of endometriosis has been reported among 14 of 76 (18%) women seeking reversal of sterilization (Dodge et al., 1986). Among patients undergoing diagnostic laparoscopy on account of chronic abdominal pain, the incidence varies between 4 and 65% and the literature on this is reviewed in Table III. Although data on the prevalence of endometriosis in the general population are not conclusive, the incidence has been suggested to be as low as 0.1 % (Blinick and Merendino, 1981) but among patients undergoing 544
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gynaecological laparotomies, the incidence can be as high as 20% (for review see Table IV). Most of the studies referred to here are retrospective, but there are three recent exceptions. Moen (1987) reported a group of 108 women undergoing laparoscopic sterilization where
Table I. Laparoscopic diagnosis of endometriosis among infertile women: review of literature Reference
Total No. with Per cent with number endometriosis endometriosis
Peterson and Behrman (1970) 204 Duignan et al. (1972) 1° Infertility 520 2° Infertility 155 Liston et al. (1972) 312 Pent (1972) 22 Goldenberg and Magendantz (1976) 112 Hasson (1976) 66 Cohen (1976) 1380 Musich and Behrman (1982) 1° Infertility 130 2° Infertility 52 Strathy et al (1982) 1° Infertility 60 2° Infertility 40 Nordenskjold and Ahlgren (1983) 1° Infertility 307 2° Infertility 126 Chang et al. (1987) 1° Infertility 1140 2° Infertility 913 Mahmood and Templeton (1989) 1° Infertility 292 2° Infertility 198 Total 6029 Primary infertility 276/2449 = (11%) Secondary infertility 74/1484 = (5%)
70
33
45 7 25 1 29 15 320
9 5 8 5 26 23 23
50 13
39 25
16 5
27 13
62 7
2 6
28 16
3 2
75 26 810
26 13 13
Table II. Prevalence of endometriosis among previously fertile patients undergoing sterilization: review of literature Reference
Total
No. with endometriosis
Per cent with endometriosis
Hasson (1976) Drake and Grunert (1980) Strathy el al. (1982) Liu and Hitchcock (1986) Moen (1987) Kirshon and Poindexter (1988) Total
296 43 200 75 108 566 1288
4 2 4 32 19 42 163
1 5 2 43 18 7 8
- Oxford University Press
Prevalence and genesis of endometriosis
endometriosis was noted in 18%, while Liu and Hitchcock (1986) reported an incidence of 43 % (mild endometriosis only) in a group of 75 patients where laparoscopic sterilization was performed during the days of menstruation. The third study (Mahmood and Templeton, 1989) was among infertile women. The purpose of the present study was to document prospectively, using a defined protocol, the prevalence of endometriosis among Caucasian fertile and infertile pre-menopausal women, and to evaluate factors such as contraceptive practice and reproductive history, which may play a role in the natural history of the disease.
Table HI. Prevalence of endometriosis among women undergoing laparoscopy for abdominal pain: review of literature Reference
Total
No. with endometriosis
Per cent with endometriosis
Blunt (1972) Condos (1972) Duignan et al. (1972) Liston et al. (1972) Pent (1972) Lindberg et al. (1973) Bullock et al. (1974) Kleppinger (1974) Talbot and Leeton (1974) Chatman (1976) Hasson (1976) Hayden and Soderstrom (1977) Chatman and Ward (1982) Goldstein et al. (1980) Kresch et al. (1984) Chang et al. (1987) Total
41 76 135 134 38 95 18 28 85 260 45 485 43 140 100 45 1908
9 3 11 6 7 12 9 2 18 59 4 153 28 74 32 19 446
22 4 8 5 18 14 50 7 21 23 9
32 65 53 32 42 23
Table IV. Prevalence of endometriosis among women undergoing gynaecological operations: review of literature (laparoscopies are not included) Reference
Total no. («)
No. with endometriosis
Per cent with endometriosis
d
296 1453 15 975 4500 1991 4471 580 2510 127 2976 978 928 145 1706 1223 2000 41 849
64 15 128 459 179 4 92 45 7 6 192 93 23 7 208 374 1896
22 1 1 10 9 0.1 16 2 6 02 20 10 16 0.4 17 19 5
Sampson (1924) Long and Strecker (1939) Fallas and Rosenblum (1940) Haydon (1942) Kelly and Schlademan (1949) b Blmick and Merendino (1981) McCall and Dolan (1956) Cruz (1951) Moore et al. (1967) b Aimakhu and Osunkoya (1971) c Williams (1975) Hayden and Soderstrom (1977) d William and Pratt (1977) b Ekwempu and Harrison (1979) Puolakka et al. (1980) Weed and Arquembourg (1980) Total a
Ovarian endometriosis. Black patients only Only abdominal hysterectomies ^Women over 55 years of age. b
c
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Materials and methods Four groups of patients, totalling 1542 women were evaluated prospectively. Group 1 included 654 women having laparoscopy because of infertility. Group 2 included 598 previously fertile women having laparoscopic sterilization. Group 3 included 156 women (117 previously fertile and 39 voluntarily infertile) having laparoscopic evaluation because of chronic abdominal pain. Group 4 included 134 previously fertile women having total abdominal hysterectomy for dysfunctional uterine bleeding (DUB). The menstrual pattern and symptomatology have been described elsewhere (Mahmood et al., 1991). The laparoscopies were carried out by six and the hysterectomies by three experienced surgeons, who performed the procedures according to the study protocol and recorded their findings on the preprinted sheet. All these operations were performed during the follicular phase, mainly between days 5-12 of the cycle. All laparoscopies were performed under general anaesthesia with endotracheal intubation and using a double puncture technique. A 10 mm end-viewing laparoscope was introduced through an infra-umbilical incision and a modified Palmer-Jacob's forceps was introduced suprapubically for manipulation. The pelvis was systematically inspected; initially the uterus was held in acute retroversion and the anterior surface of the uterus, uterovesicle reflection and all the peritoneal surfaces, as far as the insertion of round ligaments laterally, and the anterior surface of the broad ligament were inspected. Then the uterus was held in acute anteversion and the posterior surface of the uterus, uterosacral ligaments, pouch of Douglas and rectovaginal septum were inspected and free fluid from that area was aspirated. The posterior leaf of the broad ligament was also inspected on both sides. Both Fallopian tubes were inspected along their entire length; their mobility, presence of peritubal adhesions or tubal distortion, and functional relationship of fimbria to the ovaries was noted. Both ovaries were mobilized to look for the presence of endometriosis on the undersurfaces and also periovarian adhesions. The diagnosis of endometriosis was based on the characteristic visual presentation of the disease and biopsies were not taken. All endometriotic deposits were documented on a preprinted drawing of pelvic organs for each patient and the extent of endometriosis was scored using the Revised American Fertility Society Classification (1985). In this system a score < 5 signifies minimal endometriosis, 6 - 1 5 mild endometriosis, 16-40 moderate endometriosis and a score of >40 indicates severe endometriosis. Among infertile patients, tubal patency was confirmed by the transcervical injection of 0.5% methylene blue dye in isotonic saline using a Leach Wilkinson cannula. Patients undergoing laparoscopic sterilization had tubal occlusion performed with Filshie Clips, applied ~2.5 cm distal to the cornual end of the tube. Among patients undergoing abdominal hysterectomies, only endometriotic deposits noted at the time of operation were documented on the data sheet; histologically proven lesions (i.e. adenomyosis or other focal microscopic deposits on the histology specimen) were not considered in the data analysis. All the women were asked to complete a questionnaire at home regarding contraceptive practice and previous obstetric history. 545
T.A.Mahmood and A.Templeton
varying from 22% in women having laparoscopic sterilization, 28% in women with infertility and those being investigated for pelvic pain and 21% in women undergoing abdominal hysterectomy for DUB (Table V). The grade of endometriosis is shown in Table VI. The majority of patients in all the study groups with endometriosis had mild disease (range 65—88%; mean = 71%). There were 13 cases (10%) of severe endometriosis among patients attending for infertility evaluation compared to only one case in the hysterectomy group and none in the other two groups, however the difference in the severity of the disease among the four groups did not reach statistical significance (x2 = 1.854; d.f. 6; P = NS). The pelvic site of the endometriosis in each study group is shown in Table VII. A higher proportion of infertile women had utero-vesicle peritoneal involvement with endometriosis compared to the other three groups. There were no other significant differences between groups. It should be noted that a few patients had endometriotic deposits at more than one site in the pelvis. Among 102 women who had previous laparoscopic tubal electrocautery (45 in the laparoscopy for pelvic pain group and 57 in the hysterectomy group), 13 were noted to have endometriosis at repeat assessment, 7/45 (16%) in the laparoscopy group and 6/57 (11%) in the hysterectomy group. The reproductive history of all patients with endometriosis, regardless of original groups, was then compared with those with no endometriosis. The accumulated data are shown in Table VIE. Women with endometriosis were significantly younger in age at menarche, younger in age at first pregnancy, had a shorter duration of contraceptive use prior to first pregnancy, shorter
Statistical analysis 2
2
Statistical evaluation was performed using x test, x test with Yate's correction, and analysis of variance (F) using the SPSS-X statistical package on mainframe computer. Results The incidence of endometriosis in the previously fertile population varied from 6% in the sterilization group to 25% in the hysterectomy group compared to 21% noted in the infertile population. Of the 654 infertile women evaluated, 400 women had primary infertility and 254 had secondary infertility; the incidence of endometriosis was 24.5% (98/400) and 14% (35/254) respectively in these groups. The incidence of postinfective pelvic adhesions was observed in all study groups,
Table V. Prevalence of endometriosis in the fertile and infertile population Study groups
n
Laparoscopy for infertility
654 (100%) Laparoscopic sterilization 598 (100%) Laparoscopy for abdominal pain 156 (100%) Abdominal hysterectomy for 134 dysfunctional uterine bleeding (100%) Grand total 1542 (100%)
Normal Pelvic Endometriosis pelvis adhesions 339 (57%) 432 (72%) 89 (57%) 73 (54%) 933 (60%)
182 (28%) 129 (22%) 43 (28%) 28 (21%) 382 (25%)
133 (21%) 37 (6%) 24 (15%) 33 (25%) 227 (15%)
Table VI. Severity of endometriosis (according to revised AFS scoring*) among those women with endometriosis in four study groups Study group
Severity of endometriosis
Laparoscopy for infertility (n = 133) Laparoscopic sterilization (n = 37) Laparoscopy for abdominal pain (n = 24) Abdominal hysterectomy (n = 33) Total 227 (100%)
Minimal/mild endometriosis
Moderate endometriosis
Severe endometriosis
86 30 21 25 162
34 7 3 7 51
13 (10%)
(65%) (81%) (88%) (76%) (72%)
(25%) (19%) (12%) (21%) (23%)
I (3%) 14 (6%)
*AFS, American Fertility Society: minimal = < 5 . mild = 6 - 1 5 , moderate = 16—40. severe = >40.
Table VII. Pelvic site of endometriosis in each study group Study groups
One ovary
Both ovaries
Pouch of Douglas
Utero-vesicle reflection
Other peritoneal sites in the pelvis
Endometriosis laparoscopy for infertility
37 (28%) 11 (30%) 2 (8%) 11 (33%) X 2 5 03 d.f = 3 P = NS
20 (15%) 8 (22%) 2 (8%) 6 (18%) X22.OO d.f. = 3 P = NS
95 (71.5%) 29 (78%) 20 (83%) 25 (76%) X2 0.102 d.f = 3 P = NS
38 (28.5%) 3 (8%) 2 (8%) 6 (18%) X2 10.45 d.f = 3 P < 0.02
20 (15%) 5 (13 5%) 6 (25%) 7 (20%) X2 2 94 d.f. = 3 P = NS
Endometriosis laparoscopic sterilization Endometriosis pain group Endometriosis hysterectomy group Significance
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Prevalence and genesis of endometnosis
Table VIII. A comparison of reproductive history between patients with and without endometriosis using the accumulated data (results mean ± SD: years) Variables
Endometriosis Noi endometriosis Analysis F P (n = 227) (" = 1315)
Age at present
34 n 12.54 n 20.48 n 3.05 n 5.56 n 4 83 n 5.00 n 9 63 n
Age at menarche Age at 1st pregnancy Duration of pill usage before 1st pregnancy Total use of combined contraceptive pill Total duration of IUCD* usage Barrier method Interval since last confinement
± = ± = ± = ± = ± = ± = ± = ± =
6.70 227 1.53 227 3.60 98 1 68 98 3 34 162 3 72 29 4.77 24 7.11 156
33.5 n 13. 07 n 21. 84 n 4..11 n 8..04 n 3..62 n 5..53 n 6..80 n
± = ± = ± = ± = ± = ± = ± = ± =
6.20 1315 1.58 1315 4.20 1106 2.88 615 3.15 863 3.12 335 3.90 139 4 77 1106
0.90
NS
3.89 < 0.05 7.24 < 0.025 4.45 < 0 05 16 03 = 0.005 3.60 < 0 10 (NS) 0.184 NS 18.94 < 0.005
total duration of pill use, longer interval since last confinement and longer duration of intrauterine contraceptive device (IUCD) use. Discussion The purpose of this study was to examine the prevalence of endometriosis in a large sample of fertile and infertile women. As shown in Tables I-IV, the reported incidence of endometriosis varies from as low as 2% to as high as 52% in the infertile population and from 1 to 43 % among previously fertile women. The reason for these variations depends in part on the study population, their referral practices and the ethnic and racial background. The present study included only Caucasian patients. Endometriosis was noted to be more frequent among patients attending for infertility investigation compared to patients undergoing laparoscopic sterilization. The observed figure of 6% in the latter group is higher than that reported by Hasson (1976) and Strathy et al. (1982) but much lower than the 43% of 75 patients reported by Liu and Hitchcock (1986) and the 18% of 108 women reported by Moen (1987). However endometriosis was noted in 25% of previously fertile women undergoing abdominal hysterectomy. The high incidence of endometriosis in this group may be related to the menstrual symptoms, resulting in hysterectomy. Among patients being investigated for chronic abdominal pain, the incidence of endometriosis was 15% while 28% had evidence of chronic pelvic inflammatory disease. Chatman and Ward (1982) reported endometriosis in 65% and pelvic adhesions in 23% of black teenagers who had laparoscopy because of disabling pelvic pain or dysmenorrhoea, while Goldstein et al. (1980) in a group of 140 adolescents with chronic abdominal pain reported endometriosis in 52% and pelvic adhesions in 20%. The site of endometriosis is of some interest here. All groups were comparable as regards ovarian involvement. The Pouch of Douglas was involved in 83% of patients in the pain group but this high incidence was not significantly different to that of the
other three groups. This finding is of interest because Goldstein et al. (1980) reported that the majority of patients in their study group (pelvic pain) had pelvic tenderness with or without nodularity of uterosacral ligaments. However in this study population, a similar proportion of apparently asymptomatic patients in the sterilization group and the infertility group also had these deposits. Data on menstrual symptomatology in women with endometriosis has been described elsewhere (Mahmood and Templeton, 1990; Mahmood et al., 1991). When endometriosis was diagnosed in this study, the disease was almost always of the mild or moderate variety and only among the infertile women was there a significant incidence of severe endometriosis. Thus, while the relationship between severe disease and infertility is accepted and can be readily understood, the not infrequent finding of mild disease in the previously fertile population calls into question the casual association between mild endometriosis and infertility. The genesis of pelvic endometriosis is not clearly understood and various theories have been proposed, i.e. retrograde menstruation (Sampson, 1924), lymphatic and vascular metaplasia (Halban, 1925; Javert, 1949), coelemic metaplasia (Novak, 1931; Gardner et al., 1953) and deficient cellular immunity (Dmowski et al, 1981). Furthermore, Meigs (1938) proposed that endometriosis is more common in women who have had uninterrupted menstruation (early menarche, prolonged interval after confinement) for several years and Ranney (1975, 1980) believed that endometriosis tends to become progressively more severe as long as untreated women menstruate. Data reported in our study indeed point to a link between the duration of exposure to spontaneous menstruation and the genesis of endometriosis. (a) The concept of uninterrupted prolonged exposure to menstruation in patients with prolonged infertility may be of importance to the development of endometriosis. Of the 654 infertile patients in this study, a group of 25 patients with unexplained infertility who had previously normal laparoscopies, had repeat laparoscopies performed (mean interval since first laparoscopy of 3 years) and of these, three (12%) had developed minimal endometriosis. This observation is supported by a similar case, reported by Kennedy et al. (1989). (b) Endometriosis was noted in 24% of previously fertile women undergoing abdominal hysterectomy, significantly higher than the 6% observed among women undergoing laparoscopic sterilization. The high incidence of endometriosis in the former group may be related to the prolonged interval since last confinement (mean 18 years) compared to 7 years in the latter group (P < 0.001; data not shown), thereby suggesting that women with lengthy intervals of uninterrupted menstrual periods run an increased risk of developing endometriosis. Thus the difference in the occurrence of endometriosis in these two fertile groups may represent a longer period at risk. (c) The role of contraceptive practice: Buttram (1979) suggested that women using oral contraception have a diminished chance of developing endometriosis, although his study lacked suitable controls. Strathy et al. (1982) reported that among previously fertile women, endometriosis was more common among those who had not used the oral contraceptive pill. Among women being sterilized, Kirshon and Poindexter (1988) reported a 547
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T.A.Mahmood and A.Templeton significantly higher incidence of endometriosis among former intrauterine device (IUD) users. The use of oral contraceptives is associated with endometrial atrophy and Ranney (1975, 1980) speculated that these agents may inhibit or even prevent the development of endometriosis; on the other and IUD usage is associated with menorrhagia (Israel et al., 1974; Larsson et al., 1975), which may be associated with an increase of retrograde menstruation. In this study, the total duration of combined pill usage was significantly higher in patients with normal pelvis compared with those with endometriosis and conversely, the total duration of IUD usage was lower. (d) The finding of mild endometriosis in 13% of patients previously sterilized with electrocautery is of interest in further understanding the genesis of the disease. Donnez et al. (1984) reported the presence of focal endometriosis in 16% of patients previously sterilized by Pomeroy's procedure and in 26% of women previously sterilized with electrocautery. All these patients underwent total abdominal hysterectomy and bilateral salpingooophorectomy and the diagnosis was made histologically. Dodge et al. (1986) reported a series of 76 patients requesting reversal of sterilization and of these, 14 (18%) had pelvic endometriosis. Either such women had developed tubal fistulae which allows retrograde menstruation and endometrial implantation (Sampson, 1930; Rock et al, 1981; Flett et al, 1988), or microscopic implants of endometrial tissue may have been present in the pelvis and over the years of uninterrupted oestrogen stimulation, these might have led to the appearance of macroscopic endometriotic deposits (Hayden and Soderstrom, 1977; Schram, 1978). Thus, in conclusion, it is possible that among susceptible women (infertile and fertile), a prolonged interval of uninterrupted menstruation may play a causative role in the genesis of endometriosis. As Redwine (1987) has suggested, the presence of endometriosis may be a marker of some other acquired or developmental pathological state that may be related to the infertility, and which remains after the endometriosis is gone.
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Prevalence and genesis of endometriosis in 100 women with chronic pelvic pain. Obstet. Gynecol., 64, 672-674. Larsson,B-, Hamberger,L. and Rybo,G. (1975) Influence of copper intrauterine contraceptive devices (Cu 7 IUCD) on the menstrual blood loss. Acta Obsiet. Gynecol. Scand., 54, 315-318. Lindberg,W.I., Wall,J.E. and Mathers.J.E. (1973) Laparoscopy in evaluation of pelvic pain. Obstet. Gynecol., 42, 872-876. Liston,W.A., Bradford,W.P., Downie,J. and Kerr,M.G. (1972) Laparoscopy in a general gynecologic unit. Am. J. Obstet. Gynecol., 113, 672-677. Liu,D.T.Y. and Hitchcock.A. (1986) Endometriosis: Its association with retrograde menstruation, dysmenorrhoea and tubal pathology. Br. J. Obstet. Gynaecol., 93, 859-862. Long.W. and Strecker.W.E. (1939) Endometriosis: Review of incidence in 1,453 abdominal pelvic operations at St. Anthony Hospital, 1935-1937, with particular reference to identification and treatment. South Med. J., 32, 489-495. McCall,M.L. and Dolan,W.G. (1956) Experiences with pelvic endometriosis; review of private cases and patients at the Charity Hospital of Louisiana at New Orleans. New Orleans J. State Med. Soc, 108, 43-49. Mahmood,T.A. and Templeton,A.A. (1989) The relationship between endometriosis and semen analysis. A review of 490 consecutive laparoscopies. Hum. Reprod., 4, 782—785. Mahmood,T.A. and Templeton,A. (1990) Pathophysiology of mild endometriosis: review of literature. Hum. Reprod., 5, 765—784. Mahmood,T.A., Templeton.A.A., Thomson,L. and Fraser,C. (1991) Menstrual symptoms in women with pelvic endometriosis. Br.J. Obstet. Gynaecol., in press. Meigs,J.V. (1938) Endometriosis—a possible etiologic factor. Surg. Gynecol. Obstet., 67, 253-255. Moen,M.H. (1987) Endometriosis in women at interval sterilization. Acta Obstet. Gynecol. Scand., 66, 451-454. Moore.J.G., Schifrin,B.S. and Erez,S. (1967) Ovarian tumours in infancy, childhood, and adolescence. Am. J. Obstet. Gynecol., 99, 913-922. Musich,J.R. and Behrman,S.J. (1982) Infertility laparoscopy in perspective. Review of five hundred cases. Am. J. Obstet. Gynecol., 143, 293-303. Nordenskjold.F. and Ahlgren,M. (1983) Laparoscopy in female infertility. Acta Obstet. Gynecol. Scand., 62, 609-615. Novak,E. (1931) Pelvic endometriosis: Spontaneous rupture of endometrial cysts, with a report of three cases. Am. J. Obstet. Gynecol., 22, 826-837. Pent,D. (1972) Laparoscopy: Its role in private practice. Am. J. Obstet. Gynecol., 113, 459-468. Peterson,E.P. and Behrman,S.J. (1970) Laparoscopy of the infertile patient. Obstet. Gynecol., 36, 363-367. Puolakka,J., Kauppila,A. and Ronnberg,L. (1980) Results in the operative treatment of pelvic endometriosis. Acta Obstet. Gynecol Scand, 59, 429-431. Ranney,B. (1975) The prevention, inhibition, palliation and treatment of endometriosis. Am. J. Obstet. Gynecol., 123, 778—785. Ranney,B. (1980) Etiology, prevention and inhibition of endometriosis. Clin. Obstet. Gynecol., 23, 875-880. Redwine,D.B. (1987) The distribution of endometriosis in the pelvis by age groups and fertility. Fenil. SteriL, 47, 173—175. Revised American Fertility Society Classificaton of Endometriosis (1985) Fenil. SteriL, 43, 351-352. Rock,J.A., Guzick,D.S., Sengos,C.,Schweditsch,M., et al. (1981) The conservative surgical treatment of endometriosis: Evaluation of pregnancy success with respect to the extent of disease as categorized using contemporary classification systems. Fenil. SteriL, 35, 131-137. Downloaded from https://academic.oup.com/humrep/article-abstract/6/4/544/639892 by Mount Royal College user on 22 January 2018
Sampson,J.A. (1924) Benign and malignant endometrial implants in peritoneal cavity, and their relation to certain ovarian tumors. Surg. Gynecol. Obstet., 38, 287-311. Sampson,J.A. (1930) Postsalpingectomy endometriosis (endosalpingosis). Am. J. Obstet. Gynecol., 20, 443-480. SchramJ.D. (1978) Endometriosis after "pelvic cleanout". South Med. J., 71, 1419-1420. Strathy,J.H., Molgaard.C.A., Coulam.C.B. and Melton,L.J.,m (1982) Endometriosis and infertility. A laparoscopic study of endometriosis among fertile and infertile women. Fenil. SteriL, 38, 667—672. Talbot,H.M. and Leeton,J. (1974) The role of laparoscopy in 1400 patients. Med. J. Aust., 1, 3 6 - 3 8 . Weed,J.C. and Arquembourg,P.C. (1980) Endometriosis: Can it produce an autoimmune response resulting in infertility? Clin. Obstet. Gynecol., 23, 885-893. William.T.J. and Pratt,J.H. (1977) Endometriosis in 1,000 consecutive celiotomies: Incidence and management. Am. J. Obstet. Gynecol., 129, 245-250. Williams,T.J. (1975) The role of surgery in the management of endometriosis. Mayo. Clin. Proc, 50, 198-203. Received on July 11, 1990; accepted on December 13, 1990
549
Prevalence and genesis of endometriosis
Tahir A.Mahmood1 and Allan Templeton Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Cornhill Road, Aberdeen AB9 2ZD, UK 'To whom correspondence should be addressed at Forth Park Hospital, Kirkcaldy, Fife KY2 5RA, UK
A group of 1542 pre-menopausal Caucasian women were assessed prospectively to investigate the prevalence of endometriosis. The women were either having laparoscopy because of infertiilty (n = 654), undergoing laparoscopic sterilization (n = 598), having laparoscopy because of chronic abdominal and pelvic pain (n = 156) or undergoing abdominal hysterectomy for dysfunctional uterine bleeding (n = 134). Endometriosis was noted more frequently among women being investigated for infertility (21%) than among those undergoing sterilization (6%). Among those being investigated for chronic abdominal pain, the incidence of endometriosis was 15%, while among those undergoing abdominal hysterectomy, it was 25%. In all groups the total duration of combined pill usage was significantly higher in patients who had a normal pelvis compared to those with endometriosis. It is suggested that among susceptible women, both fertile and infertile, a prolonged period of regular spontaneous menstruation may play a causative role in the genesis of endometriosis. Key words: prevalence/endometriosis/fertile - infertile/genesis
Introduction Laparoscopy is now accepted as an integral part of infertility investigation and as a result, endometriosis is more frequently diagnosed in the infertile population. Its incidence varies from as low as 2 % to as high as 48 %, but the generally accepted range is 2 0 - 4 0 % . A review of the literature is presented in Table I. The prevalence of endometriosis among previously fertile women undergoing laparoscopic sterilization varies between 1 and 18% while one recent study reported an unusually high incidence of 43%. These studies are reviewed in Table II. The occurrence of endometriosis has been reported among 14 of 76 (18%) women seeking reversal of sterilization (Dodge et al., 1986). Among patients undergoing diagnostic laparoscopy on account of chronic abdominal pain, the incidence varies between 4 and 65% and the literature on this is reviewed in Table III. Although data on the prevalence of endometriosis in the general population are not conclusive, the incidence has been suggested to be as low as 0.1 % (Blinick and Merendino, 1981) but among patients undergoing 544
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gynaecological laparotomies, the incidence can be as high as 20% (for review see Table IV). Most of the studies referred to here are retrospective, but there are three recent exceptions. Moen (1987) reported a group of 108 women undergoing laparoscopic sterilization where
Table I. Laparoscopic diagnosis of endometriosis among infertile women: review of literature Reference
Total No. with Per cent with number endometriosis endometriosis
Peterson and Behrman (1970) 204 Duignan et al. (1972) 1° Infertility 520 2° Infertility 155 Liston et al. (1972) 312 Pent (1972) 22 Goldenberg and Magendantz (1976) 112 Hasson (1976) 66 Cohen (1976) 1380 Musich and Behrman (1982) 1° Infertility 130 2° Infertility 52 Strathy et al (1982) 1° Infertility 60 2° Infertility 40 Nordenskjold and Ahlgren (1983) 1° Infertility 307 2° Infertility 126 Chang et al. (1987) 1° Infertility 1140 2° Infertility 913 Mahmood and Templeton (1989) 1° Infertility 292 2° Infertility 198 Total 6029 Primary infertility 276/2449 = (11%) Secondary infertility 74/1484 = (5%)
70
33
45 7 25 1 29 15 320
9 5 8 5 26 23 23
50 13
39 25
16 5
27 13
62 7
2 6
28 16
3 2
75 26 810
26 13 13
Table II. Prevalence of endometriosis among previously fertile patients undergoing sterilization: review of literature Reference
Total
No. with endometriosis
Per cent with endometriosis
Hasson (1976) Drake and Grunert (1980) Strathy el al. (1982) Liu and Hitchcock (1986) Moen (1987) Kirshon and Poindexter (1988) Total
296 43 200 75 108 566 1288
4 2 4 32 19 42 163
1 5 2 43 18 7 8
- Oxford University Press
Prevalence and genesis of endometriosis
endometriosis was noted in 18%, while Liu and Hitchcock (1986) reported an incidence of 43 % (mild endometriosis only) in a group of 75 patients where laparoscopic sterilization was performed during the days of menstruation. The third study (Mahmood and Templeton, 1989) was among infertile women. The purpose of the present study was to document prospectively, using a defined protocol, the prevalence of endometriosis among Caucasian fertile and infertile pre-menopausal women, and to evaluate factors such as contraceptive practice and reproductive history, which may play a role in the natural history of the disease.
Table HI. Prevalence of endometriosis among women undergoing laparoscopy for abdominal pain: review of literature Reference
Total
No. with endometriosis
Per cent with endometriosis
Blunt (1972) Condos (1972) Duignan et al. (1972) Liston et al. (1972) Pent (1972) Lindberg et al. (1973) Bullock et al. (1974) Kleppinger (1974) Talbot and Leeton (1974) Chatman (1976) Hasson (1976) Hayden and Soderstrom (1977) Chatman and Ward (1982) Goldstein et al. (1980) Kresch et al. (1984) Chang et al. (1987) Total
41 76 135 134 38 95 18 28 85 260 45 485 43 140 100 45 1908
9 3 11 6 7 12 9 2 18 59 4 153 28 74 32 19 446
22 4 8 5 18 14 50 7 21 23 9
32 65 53 32 42 23
Table IV. Prevalence of endometriosis among women undergoing gynaecological operations: review of literature (laparoscopies are not included) Reference
Total no. («)
No. with endometriosis
Per cent with endometriosis
d
296 1453 15 975 4500 1991 4471 580 2510 127 2976 978 928 145 1706 1223 2000 41 849
64 15 128 459 179 4 92 45 7 6 192 93 23 7 208 374 1896
22 1 1 10 9 0.1 16 2 6 02 20 10 16 0.4 17 19 5
Sampson (1924) Long and Strecker (1939) Fallas and Rosenblum (1940) Haydon (1942) Kelly and Schlademan (1949) b Blmick and Merendino (1981) McCall and Dolan (1956) Cruz (1951) Moore et al. (1967) b Aimakhu and Osunkoya (1971) c Williams (1975) Hayden and Soderstrom (1977) d William and Pratt (1977) b Ekwempu and Harrison (1979) Puolakka et al. (1980) Weed and Arquembourg (1980) Total a
Ovarian endometriosis. Black patients only Only abdominal hysterectomies ^Women over 55 years of age. b
c
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Materials and methods Four groups of patients, totalling 1542 women were evaluated prospectively. Group 1 included 654 women having laparoscopy because of infertility. Group 2 included 598 previously fertile women having laparoscopic sterilization. Group 3 included 156 women (117 previously fertile and 39 voluntarily infertile) having laparoscopic evaluation because of chronic abdominal pain. Group 4 included 134 previously fertile women having total abdominal hysterectomy for dysfunctional uterine bleeding (DUB). The menstrual pattern and symptomatology have been described elsewhere (Mahmood et al., 1991). The laparoscopies were carried out by six and the hysterectomies by three experienced surgeons, who performed the procedures according to the study protocol and recorded their findings on the preprinted sheet. All these operations were performed during the follicular phase, mainly between days 5-12 of the cycle. All laparoscopies were performed under general anaesthesia with endotracheal intubation and using a double puncture technique. A 10 mm end-viewing laparoscope was introduced through an infra-umbilical incision and a modified Palmer-Jacob's forceps was introduced suprapubically for manipulation. The pelvis was systematically inspected; initially the uterus was held in acute retroversion and the anterior surface of the uterus, uterovesicle reflection and all the peritoneal surfaces, as far as the insertion of round ligaments laterally, and the anterior surface of the broad ligament were inspected. Then the uterus was held in acute anteversion and the posterior surface of the uterus, uterosacral ligaments, pouch of Douglas and rectovaginal septum were inspected and free fluid from that area was aspirated. The posterior leaf of the broad ligament was also inspected on both sides. Both Fallopian tubes were inspected along their entire length; their mobility, presence of peritubal adhesions or tubal distortion, and functional relationship of fimbria to the ovaries was noted. Both ovaries were mobilized to look for the presence of endometriosis on the undersurfaces and also periovarian adhesions. The diagnosis of endometriosis was based on the characteristic visual presentation of the disease and biopsies were not taken. All endometriotic deposits were documented on a preprinted drawing of pelvic organs for each patient and the extent of endometriosis was scored using the Revised American Fertility Society Classification (1985). In this system a score < 5 signifies minimal endometriosis, 6 - 1 5 mild endometriosis, 16-40 moderate endometriosis and a score of >40 indicates severe endometriosis. Among infertile patients, tubal patency was confirmed by the transcervical injection of 0.5% methylene blue dye in isotonic saline using a Leach Wilkinson cannula. Patients undergoing laparoscopic sterilization had tubal occlusion performed with Filshie Clips, applied ~2.5 cm distal to the cornual end of the tube. Among patients undergoing abdominal hysterectomies, only endometriotic deposits noted at the time of operation were documented on the data sheet; histologically proven lesions (i.e. adenomyosis or other focal microscopic deposits on the histology specimen) were not considered in the data analysis. All the women were asked to complete a questionnaire at home regarding contraceptive practice and previous obstetric history. 545
T.A.Mahmood and A.Templeton
varying from 22% in women having laparoscopic sterilization, 28% in women with infertility and those being investigated for pelvic pain and 21% in women undergoing abdominal hysterectomy for DUB (Table V). The grade of endometriosis is shown in Table VI. The majority of patients in all the study groups with endometriosis had mild disease (range 65—88%; mean = 71%). There were 13 cases (10%) of severe endometriosis among patients attending for infertility evaluation compared to only one case in the hysterectomy group and none in the other two groups, however the difference in the severity of the disease among the four groups did not reach statistical significance (x2 = 1.854; d.f. 6; P = NS). The pelvic site of the endometriosis in each study group is shown in Table VII. A higher proportion of infertile women had utero-vesicle peritoneal involvement with endometriosis compared to the other three groups. There were no other significant differences between groups. It should be noted that a few patients had endometriotic deposits at more than one site in the pelvis. Among 102 women who had previous laparoscopic tubal electrocautery (45 in the laparoscopy for pelvic pain group and 57 in the hysterectomy group), 13 were noted to have endometriosis at repeat assessment, 7/45 (16%) in the laparoscopy group and 6/57 (11%) in the hysterectomy group. The reproductive history of all patients with endometriosis, regardless of original groups, was then compared with those with no endometriosis. The accumulated data are shown in Table VIE. Women with endometriosis were significantly younger in age at menarche, younger in age at first pregnancy, had a shorter duration of contraceptive use prior to first pregnancy, shorter
Statistical analysis 2
2
Statistical evaluation was performed using x test, x test with Yate's correction, and analysis of variance (F) using the SPSS-X statistical package on mainframe computer. Results The incidence of endometriosis in the previously fertile population varied from 6% in the sterilization group to 25% in the hysterectomy group compared to 21% noted in the infertile population. Of the 654 infertile women evaluated, 400 women had primary infertility and 254 had secondary infertility; the incidence of endometriosis was 24.5% (98/400) and 14% (35/254) respectively in these groups. The incidence of postinfective pelvic adhesions was observed in all study groups,
Table V. Prevalence of endometriosis in the fertile and infertile population Study groups
n
Laparoscopy for infertility
654 (100%) Laparoscopic sterilization 598 (100%) Laparoscopy for abdominal pain 156 (100%) Abdominal hysterectomy for 134 dysfunctional uterine bleeding (100%) Grand total 1542 (100%)
Normal Pelvic Endometriosis pelvis adhesions 339 (57%) 432 (72%) 89 (57%) 73 (54%) 933 (60%)
182 (28%) 129 (22%) 43 (28%) 28 (21%) 382 (25%)
133 (21%) 37 (6%) 24 (15%) 33 (25%) 227 (15%)
Table VI. Severity of endometriosis (according to revised AFS scoring*) among those women with endometriosis in four study groups Study group
Severity of endometriosis
Laparoscopy for infertility (n = 133) Laparoscopic sterilization (n = 37) Laparoscopy for abdominal pain (n = 24) Abdominal hysterectomy (n = 33) Total 227 (100%)
Minimal/mild endometriosis
Moderate endometriosis
Severe endometriosis
86 30 21 25 162
34 7 3 7 51
13 (10%)
(65%) (81%) (88%) (76%) (72%)
(25%) (19%) (12%) (21%) (23%)
I (3%) 14 (6%)
*AFS, American Fertility Society: minimal = < 5 . mild = 6 - 1 5 , moderate = 16—40. severe = >40.
Table VII. Pelvic site of endometriosis in each study group Study groups
One ovary
Both ovaries
Pouch of Douglas
Utero-vesicle reflection
Other peritoneal sites in the pelvis
Endometriosis laparoscopy for infertility
37 (28%) 11 (30%) 2 (8%) 11 (33%) X 2 5 03 d.f = 3 P = NS
20 (15%) 8 (22%) 2 (8%) 6 (18%) X22.OO d.f. = 3 P = NS
95 (71.5%) 29 (78%) 20 (83%) 25 (76%) X2 0.102 d.f = 3 P = NS
38 (28.5%) 3 (8%) 2 (8%) 6 (18%) X2 10.45 d.f = 3 P < 0.02
20 (15%) 5 (13 5%) 6 (25%) 7 (20%) X2 2 94 d.f. = 3 P = NS
Endometriosis laparoscopic sterilization Endometriosis pain group Endometriosis hysterectomy group Significance
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Prevalence and genesis of endometnosis
Table VIII. A comparison of reproductive history between patients with and without endometriosis using the accumulated data (results mean ± SD: years) Variables
Endometriosis Noi endometriosis Analysis F P (n = 227) (" = 1315)
Age at present
34 n 12.54 n 20.48 n 3.05 n 5.56 n 4 83 n 5.00 n 9 63 n
Age at menarche Age at 1st pregnancy Duration of pill usage before 1st pregnancy Total use of combined contraceptive pill Total duration of IUCD* usage Barrier method Interval since last confinement
± = ± = ± = ± = ± = ± = ± = ± =
6.70 227 1.53 227 3.60 98 1 68 98 3 34 162 3 72 29 4.77 24 7.11 156
33.5 n 13. 07 n 21. 84 n 4..11 n 8..04 n 3..62 n 5..53 n 6..80 n
± = ± = ± = ± = ± = ± = ± = ± =
6.20 1315 1.58 1315 4.20 1106 2.88 615 3.15 863 3.12 335 3.90 139 4 77 1106
0.90
NS
3.89 < 0.05 7.24 < 0.025 4.45 < 0 05 16 03 = 0.005 3.60 < 0 10 (NS) 0.184 NS 18.94 < 0.005
total duration of pill use, longer interval since last confinement and longer duration of intrauterine contraceptive device (IUCD) use. Discussion The purpose of this study was to examine the prevalence of endometriosis in a large sample of fertile and infertile women. As shown in Tables I-IV, the reported incidence of endometriosis varies from as low as 2% to as high as 52% in the infertile population and from 1 to 43 % among previously fertile women. The reason for these variations depends in part on the study population, their referral practices and the ethnic and racial background. The present study included only Caucasian patients. Endometriosis was noted to be more frequent among patients attending for infertility investigation compared to patients undergoing laparoscopic sterilization. The observed figure of 6% in the latter group is higher than that reported by Hasson (1976) and Strathy et al. (1982) but much lower than the 43% of 75 patients reported by Liu and Hitchcock (1986) and the 18% of 108 women reported by Moen (1987). However endometriosis was noted in 25% of previously fertile women undergoing abdominal hysterectomy. The high incidence of endometriosis in this group may be related to the menstrual symptoms, resulting in hysterectomy. Among patients being investigated for chronic abdominal pain, the incidence of endometriosis was 15% while 28% had evidence of chronic pelvic inflammatory disease. Chatman and Ward (1982) reported endometriosis in 65% and pelvic adhesions in 23% of black teenagers who had laparoscopy because of disabling pelvic pain or dysmenorrhoea, while Goldstein et al. (1980) in a group of 140 adolescents with chronic abdominal pain reported endometriosis in 52% and pelvic adhesions in 20%. The site of endometriosis is of some interest here. All groups were comparable as regards ovarian involvement. The Pouch of Douglas was involved in 83% of patients in the pain group but this high incidence was not significantly different to that of the
other three groups. This finding is of interest because Goldstein et al. (1980) reported that the majority of patients in their study group (pelvic pain) had pelvic tenderness with or without nodularity of uterosacral ligaments. However in this study population, a similar proportion of apparently asymptomatic patients in the sterilization group and the infertility group also had these deposits. Data on menstrual symptomatology in women with endometriosis has been described elsewhere (Mahmood and Templeton, 1990; Mahmood et al., 1991). When endometriosis was diagnosed in this study, the disease was almost always of the mild or moderate variety and only among the infertile women was there a significant incidence of severe endometriosis. Thus, while the relationship between severe disease and infertility is accepted and can be readily understood, the not infrequent finding of mild disease in the previously fertile population calls into question the casual association between mild endometriosis and infertility. The genesis of pelvic endometriosis is not clearly understood and various theories have been proposed, i.e. retrograde menstruation (Sampson, 1924), lymphatic and vascular metaplasia (Halban, 1925; Javert, 1949), coelemic metaplasia (Novak, 1931; Gardner et al., 1953) and deficient cellular immunity (Dmowski et al, 1981). Furthermore, Meigs (1938) proposed that endometriosis is more common in women who have had uninterrupted menstruation (early menarche, prolonged interval after confinement) for several years and Ranney (1975, 1980) believed that endometriosis tends to become progressively more severe as long as untreated women menstruate. Data reported in our study indeed point to a link between the duration of exposure to spontaneous menstruation and the genesis of endometriosis. (a) The concept of uninterrupted prolonged exposure to menstruation in patients with prolonged infertility may be of importance to the development of endometriosis. Of the 654 infertile patients in this study, a group of 25 patients with unexplained infertility who had previously normal laparoscopies, had repeat laparoscopies performed (mean interval since first laparoscopy of 3 years) and of these, three (12%) had developed minimal endometriosis. This observation is supported by a similar case, reported by Kennedy et al. (1989). (b) Endometriosis was noted in 24% of previously fertile women undergoing abdominal hysterectomy, significantly higher than the 6% observed among women undergoing laparoscopic sterilization. The high incidence of endometriosis in the former group may be related to the prolonged interval since last confinement (mean 18 years) compared to 7 years in the latter group (P < 0.001; data not shown), thereby suggesting that women with lengthy intervals of uninterrupted menstrual periods run an increased risk of developing endometriosis. Thus the difference in the occurrence of endometriosis in these two fertile groups may represent a longer period at risk. (c) The role of contraceptive practice: Buttram (1979) suggested that women using oral contraception have a diminished chance of developing endometriosis, although his study lacked suitable controls. Strathy et al. (1982) reported that among previously fertile women, endometriosis was more common among those who had not used the oral contraceptive pill. Among women being sterilized, Kirshon and Poindexter (1988) reported a 547
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T.A.Mahmood and A.Templeton significantly higher incidence of endometriosis among former intrauterine device (IUD) users. The use of oral contraceptives is associated with endometrial atrophy and Ranney (1975, 1980) speculated that these agents may inhibit or even prevent the development of endometriosis; on the other and IUD usage is associated with menorrhagia (Israel et al., 1974; Larsson et al., 1975), which may be associated with an increase of retrograde menstruation. In this study, the total duration of combined pill usage was significantly higher in patients with normal pelvis compared with those with endometriosis and conversely, the total duration of IUD usage was lower. (d) The finding of mild endometriosis in 13% of patients previously sterilized with electrocautery is of interest in further understanding the genesis of the disease. Donnez et al. (1984) reported the presence of focal endometriosis in 16% of patients previously sterilized by Pomeroy's procedure and in 26% of women previously sterilized with electrocautery. All these patients underwent total abdominal hysterectomy and bilateral salpingooophorectomy and the diagnosis was made histologically. Dodge et al. (1986) reported a series of 76 patients requesting reversal of sterilization and of these, 14 (18%) had pelvic endometriosis. Either such women had developed tubal fistulae which allows retrograde menstruation and endometrial implantation (Sampson, 1930; Rock et al, 1981; Flett et al, 1988), or microscopic implants of endometrial tissue may have been present in the pelvis and over the years of uninterrupted oestrogen stimulation, these might have led to the appearance of macroscopic endometriotic deposits (Hayden and Soderstrom, 1977; Schram, 1978). Thus, in conclusion, it is possible that among susceptible women (infertile and fertile), a prolonged interval of uninterrupted menstruation may play a causative role in the genesis of endometriosis. As Redwine (1987) has suggested, the presence of endometriosis may be a marker of some other acquired or developmental pathological state that may be related to the infertility, and which remains after the endometriosis is gone.
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