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Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis
Pmsta.@dins Leukotrienes and Essential Fatty Acids (1992) 46, 133-137 @ Longman Group UK Ltd 1992
Correlation Between Dysmenorrheic Severity and Prostaglandin Production in Women with Endometriosis H. Koike, H. Egawa, T. Ohtsuka,
M. Yamaguchi,
T. Ikenoue and N. Mori
Department of Obstetrics and Gynecology, Miyazaki Medical College, Kiyotake, Miyazaki 889-16, Japan (Reprint requests to HK) ABSTRACT. The role of prostaglandhis (PCs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myome&huu, adenomyosis, normal ovary and e&ometW cyst were incubated. bKeto-FGFt, (a metabolite of PGI2), TXBz (a metabolite of TXA2), PGF zo6and PGQ concentrations of the incubation medhun were measured by RIA. The results showed that Cketo-PGFi, production in adenomyosis and endometrial cyst were signilicantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PCs production in tissue in endometriosis was observed.
INTRODUCTION
associated with dysmenorrhea, a clear cause-andeffect relationship has not been established (10). The aim of this study was to evaluate the relationship between dysmenorrheic severity and PG production by tissues of uterus and ovary in endometriosis.
Dysmenorrhea is defined as pelvic pain around the time of menstruation. The painful cramps associated with menstrual cycles experienced by many women are thought to be prostaglandin (PG) related (l-3). However, a causal relationship between dysmenorrheic severity and PGs has yet to be established. Pickles et al (4) suggested as early as 1965 that prostaglandins might play a role in the etiology of dysmenorrhea. Their hypothesis was based on the finding that dysmenorrheic women had a higher concentration of PGF2, in menstrual fluid than did normal women (5). It has been reported that disease severity does not correlate with the degree of dysmenorrhea (6) and that many women with endometriosis do not complain of dysmenorrhea (7). Dysmenorrhea is characterized by an increased concentration of both PGFz~ and PGE2 in menstrual fluid and therefore suppression of PG synthesis has become the main treatment (8). Non-steroidal antiinflammatory drugs which inhibit PG synthesis give relief in disorders of menstruation such as dysmenorrhea and menorrhagia (9). After the report of Pickles et al (4) the PG family expanded not only to PGF2, and PGE2, but also to arachidonic acid metabolites including PG12 and thromboxane (TX). It appears that, although endometriosis is
SUBJECTS AND METHODS Subjects 26 sexually active women who underwent total abdominal hysterectomy and oophorocystectomy for endometriosis were studied. Final diagnosis was confirmed by postsurgical histologic examination. Patients’ ages were 27-51 with a mean age of 41.4. They received no hormones and PG synthetase inhibitors in the cycle preceding operation. Written informed consent was obtained from all patients. Patients were divided into three groups with severe, mild and non dysmenorrhea according to the grade of complaint. Severely dysmenorrheic women required both analgesics and bed rest, while mild dysmenorrheic patients needed only analgesics. Endometrium was classified as menstrual, proliferative and secretory phases by endometrial histology (11). Methods The uterus was opened immediately after extirpation, and myometrium of uterus and ovarian tissue were carefully removed and placed in O.lM Tris
Date received 9 September 1991 Date accepted 13 November 1991 133
134
Prostaglandins Leukotrienes and Essential Fatty Acids
HCl buffer at 4°C. Samples were sliced about 0.2 mm thick and wet weight was 100 mg. Specimens were incubated in O.lM Tris HCl buffer (pH 7.4, 37°C). Incubation medium was changed after the first 15 min to eliminate traumainduced release of PGs, then incubation was continued in fresh medium for 30 min. Medium was replaced every 30 min for 2 h. After incubation, medium was centrifuged at 500 X g for 10 min. The supematant was frozen at -20°C until assay. 6-KetoPGF1,, TXB2, PGFZ, and PGE2 in the supematant were measured by direct RIA. Prostaglandin production was highest in the first 30 min, decreasing gradually according to incubation time in vitro. PG production was shown by the value in the first 30 min and expressed as pg/mg wet weight/30 min. The assay sensitivity was 2 pg, and intra- and interassay coefficients of variation for 6keto-PGFi, were respectively 7.2% and 9.8%, for TXB2 8.5% and 10.3%, for PGFz~ 6.6% and 8.8%, and for PGE2 5.9% and 7.4% (n = 18 and 20 for each PG).
6 - keto PGF,.
TXB, P< 0.05
p < 0.005 r&g
PS/W 1. *. 130 nl”
1. *. no .I”
pglm8 1. *.I30
PGEz
PGF,.
lin
w/w
1. . . I30 nnn NS
NS
1.6 1.4 -
I
28
-
1.2 1.0 -
Statistics Statistical t-test.
analysis
was performed
by Student’s
RESULTS Prostaghxndin production in endometrial cyst aud correlation between dysmenorrhea and PG production As shown in Figure 1, PG production by endometrial cysts was higher than that by normal ovary. Especially there were significant differences in 6-keto-PGF$, and TKR;? production between endometrial cyst and normal ovary. Concerning the correlation between degree of dysmenorrhea and PG production of tissue in endometrial cysts, there was a significant’ difference between mild dysmenorrhea and non dysmenorrhea in 6-keto-PGFi, production., I+wever, there was no significant difference between severe dysmenorrhea and mild dysmenorrhea in 6-keto-PGFi, production. (Fig. 2)
0
Normal
ovary
Endometrial
cyst
Fig. 1 Prostaglandin production of tissue in normal ovary and endometrial cyst. (M + SEM)
pg/mg w. w./30 min
ProstaghunIin production in adenomyosis and correlation between dysmenorrhea and PG production As shown in Figure 3, PG production by adenomyosis was higher than that by normal myometrium. There was a significant difference in 6-keto-PGF;, production between adenomyosis and normal myometrium. Figure 4 shows the correlation between the degree of dysmenorrhea and prostaglandin production of tissue in adenomyosis.
Fii. 2 Correlation between degree of dysmenorrhea and 6-keto PGF,, production of tissue in endometrial cyst. (M f SEM)
Role of PGs in Dysmenorrhea 6 - keto ~glna w
I
of Endometriosis
TXB,
PGF, .
130min P < 0.02 5P < 0.02 4pg/mg *
1. I30 nin
h!LL% Menstrual
Proliferative
Menstrual
Secretorv
PdW1.
Menstrual
Proliferative
Normal
0
Fig. 3
Prostaglandin
w.130
Proliferative
Secretory
Proliferative
Secretorv
NS
ml”
Secretorv
Menstrual
myometrlum
Adenomvosis
production of tissue in normal myometrium and adenomyosis during menstrual cycle. (M + SEM)
pg/mg 1. w. I30 mln D c 0.01 ,
lo-
I
pg/mg w. w. /30 min
. S-
p < 0.05
Pghg w. 1. I30 Rl” .
8.
12 5 4 -
5 I-
I
1
0
11
p < 0.005 I
1
3 2 l-
6 pglmg
w. I30
1.
lin
4 p < 0.02 .3
t
-
Ff. 4 Correlation between degree of dysmenorrhea prostaglandin production of tissue in adenomyosis. (M f SEM)
and
Fii. 5 Correlation between degree of dysmenorrhea 6-keto-PGF,mB, ratio of tissue in adenomyosis. (M + SEM)
and
135
136
Prostaglandins Leukotrienes
and Essential Fatty Acids
There was a significant difference in 6-keto-PGFr, production between severe dysmenorrhea and non dysmenorrhea. We compared the degree of dysmenorrhea with TXB2, PGF2, and PGEz production of tissue in adenomyosis. There were also significant correlations between severe dysmenorrhea and non dysmenorrhea for three kinds of eicosanoid production (Fig. 4). The relationship between the degree of dysmenorrhea and the 6-keto-PGFr&%& ratio of tissue in adenomyosis was also significant (Fig. 5).
DISCUSSION Human reproductive organs are important sites of PG synthesis. In addition, ectopic endometrium has been shown to produce PGs that may contribute to the pathophysiology of endometriosis and adenomyosis (12, 13). The present study shows that tissues of endometrial cyst and adenomyosis produce higher amounts of PGs than normal ovary and myometrium, particularly significantly higher amounts of 6-keto-PGFi,. Furthermore, there was a direct correlation between the degree of dysmenorrhea and PG production of tissue in endometriosis, particularly in adenomyosis. Chan reported that the severity of dysmenorrhea is better correlated to the ratio of menstrual PGF2, : PGE 2 than to the concentration of menstrual PGFza. Dysmenorrhea may be caused by either an elevated PGFz@ production or a relative deficit of PGE2 (14, 15). Yen reported that the PGF2, levels in the serum of dysmenorrheic patients were 4 times higher than those of normal women (16). It is known that endometrial tissue produces 6-keto-PGF;, and TXBz in vitro (17). The severity of symptoms of endometriosis has not always correlated well with the anatomic extent of the disease. This lack of correlation may be due to variations in the metabolic activity of endometriotic implants present at different stages of the disease (12). Vernon speculated that lesions producing large amounts of PG were ‘early’ implants with increased numbers of functional glands present (12). ‘Early’ implants may be pathologically more influential than ‘older’ implants. In this study, there were significant differences in 6-keto-PGI$,, TXB;!, PGF2, and PGE2 production between severe dysmenorrhea and non dysmenorrhea. It is possible to speculate from this study that ‘early’ implants cause severe dysmenorrhea and ‘older’ implants cause mild or no dysmenorrhea. Accordingly, tissue of adenomyosis with severe dysmenorrhea produces larger amounts of PGs. It has been reported that both local and circulating hormones interfere with smooth muscle tonus of
the uterine artery. It has also been concluded that uterine blood flow may be regulated not only by myometrial effects for example of PGs and catecholamines, but also by the action these substances exert on the uterine vascular bed itself. There seems to be a balancing action between PG12 and vasoconstricting compounds such as PGE2 and/or PGFz~. A disturbance of this mechanism may well be a hitherto unknown pathophysiological factor in the development of dysmenorrhea (18). PG12 is able to inhibit the spasms induced by PGF2, (19). The present data are in accordance with those of Omini et al (19), which indicate that PGI;! in fact has an inhibitory effect on isolated human myometrium. Wilhelmsson et al found that PG12 has a potent relaxing effect on uterine arteries which suggested that this substance may be involved in the control of uterine hemodynamics (20). This is the first report of a significant direct correlation between dysmenorrheic severity and PG production of tissue in endometriosis. The mechanism of enhanced PGIZ production in relation to dysmenorrhea is still unclear, and further study is necessary to elucidate the pathophysiological role of PG12 in endometriosis.
Acknowledgements The authors would like to thank ON0 Pharmaceutical Co Ltd, Osaka, Japan, for a generous supply of authentic prostaglandins and antisera.
References 1. Dawood M Y. Dysmenorrhea. Clin Obstet Gynecol 26: 719-727,1983 2. Ylikorkala 0, Dawood M Y. New concepts in dysmenorrhea. Am J Obstet Gynecol 130: 833-847, 1978 3. Rosenwaks Z, Seegar-Jones G. Menstrual pain. Its origins and pathogenesis. S Reprod Med 25: 207, 1980 4. Pickles V R, Hall W J, Best F A, Smith G N. Prostaglandins in endometrium and menstrual fluid from normal and dysmenorrheic subjects. J Obstet Gynecol Br Common W. 72: 185-192, 1965 5. Lundstrom V. Green K. Endoeenous levels of prostaglandin’F*, and its main hetabolites in plasma and endometrium of normal and dysmenorrheic women. Am J Obstet Gynecol 130: 640+X6,1978 6. Chacho K J, Chacho M S, Andersen P J, Scommegna A. Peritoneal fluid in patients with and without endometriosis: Prostanoids and macrophages and their effects on the spermatozoa penetration assay. Am J Obstet gynecol 154: 1290-1299,1986 7. Stevenson C S, Camnbell C G. The svmntoms. physical findings, and clinical diagnosis of pelvic endometriosis. Clin Obstet Gvnecol 3: 441-445. 1960 8. Lumsden M A, Kelly R W, Baird D T. Primary dysmenorrhoea: The importance of both prostaglandin E, and F& Br J Obstet Gynaecol 90: 1135-1140,1983
Role of PGs in Dysmenorrhea 9. Schwartz A, Zor U, Lindner H R, Naor S. Primary
10.
11. 12.
13.
14.
15.
dysmenorrhoea. Alleviation by an inhibitor of prostaghmdin synthesis and action. Obstet Gynecol 44: 709-712,1974 Burns W N, Schenken R S. Pathophysiology. In: Schenken R S fEdsI Endometriosis. Contemoorarv concepts in clinical ‘management. Philadelphia: J B Lippincott Co. pp 89, 1989 Noyes R W, He& A I, Pock J. Dating the endometrial bioosv. Fertil Steril 1: 3-25. 1950 Vernon M W, Beard J S, Graves K, Wilson E A. Classification of endometriotic implants by morphologic appearance and capacity to synthesize urostaelandin F. Fertil Steril46: 801-806. 1986 Drake-T S, O’Brien W F, RamweIl P W; Metx S A. Peritoneal fluid thromboxane B, and 6-keto-prostaglandin F,, in endometribsis. Am J Obstet Gvnecol140: 401-404. 1981 Chan W Y. Prostaglandins and non-steroidal anti-inflammatory drugs in dysmenorrhea. Annu Rev Pharmacol Toxicol23: 131-149, 1983 Bygdeman M, Bremme K, Gillespie A, Lundstrom V. Effects of the prostaglandins on the uterus.
16.
17.
18.
19.
20.
of Endometriosis
Prostaglandins and uterine contractility. Acta Obstet Gynecol Stand Suppl87: 33-38, 1979 Yen S S C. The human menstrual cycle. In: Yen S S C and Jaffe R B, Eds. Reproductive endocrinology, 2nd edn. Philadelphia: W B Saunders, 126-151, 1986 Ylikorkala 0, Viinikka L. Prostaglandins and endometriosis. Acta Obstet Gynecol Stand Suppl 113: 105-107,1983 Wilhelmsson L, Lindblom B, Wikland M, Hamberaer L. Norstrom A. Wiavist N. PGI, mav play a rgle in’the pathophysiology of L ’ dysmenorrhea. Acta Obstet Gynecol Stand Suppl, 113: 69-70, 1983 Omini C, Pasargikhan R, Folco G C, Fano M, Berti F. Pharmacological activity of PGI, and its metabolite 6-oxo-PGF,, on human uterus and fallopian tubes. ProstagIandins 15: 1045-1053, 1978 Wilhelmsson L. Wikland M. Wiavist N. PGH,. TXA, and PGI, have potent and differentiated actions on human uterine contractility. Prostaglandins 21: 277-286, 1981
137
Correlation Between Dysmenorrheic Severity and Prostaglandin Production in Women with Endometriosis H. Koike, H. Egawa, T. Ohtsuka,
M. Yamaguchi,
T. Ikenoue and N. Mori
Department of Obstetrics and Gynecology, Miyazaki Medical College, Kiyotake, Miyazaki 889-16, Japan (Reprint requests to HK) ABSTRACT. The role of prostaglandhis (PCs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myome&huu, adenomyosis, normal ovary and e&ometW cyst were incubated. bKeto-FGFt, (a metabolite of PGI2), TXBz (a metabolite of TXA2), PGF zo6and PGQ concentrations of the incubation medhun were measured by RIA. The results showed that Cketo-PGFi, production in adenomyosis and endometrial cyst were signilicantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PCs production in tissue in endometriosis was observed.
INTRODUCTION
associated with dysmenorrhea, a clear cause-andeffect relationship has not been established (10). The aim of this study was to evaluate the relationship between dysmenorrheic severity and PG production by tissues of uterus and ovary in endometriosis.
Dysmenorrhea is defined as pelvic pain around the time of menstruation. The painful cramps associated with menstrual cycles experienced by many women are thought to be prostaglandin (PG) related (l-3). However, a causal relationship between dysmenorrheic severity and PGs has yet to be established. Pickles et al (4) suggested as early as 1965 that prostaglandins might play a role in the etiology of dysmenorrhea. Their hypothesis was based on the finding that dysmenorrheic women had a higher concentration of PGF2, in menstrual fluid than did normal women (5). It has been reported that disease severity does not correlate with the degree of dysmenorrhea (6) and that many women with endometriosis do not complain of dysmenorrhea (7). Dysmenorrhea is characterized by an increased concentration of both PGFz~ and PGE2 in menstrual fluid and therefore suppression of PG synthesis has become the main treatment (8). Non-steroidal antiinflammatory drugs which inhibit PG synthesis give relief in disorders of menstruation such as dysmenorrhea and menorrhagia (9). After the report of Pickles et al (4) the PG family expanded not only to PGF2, and PGE2, but also to arachidonic acid metabolites including PG12 and thromboxane (TX). It appears that, although endometriosis is
SUBJECTS AND METHODS Subjects 26 sexually active women who underwent total abdominal hysterectomy and oophorocystectomy for endometriosis were studied. Final diagnosis was confirmed by postsurgical histologic examination. Patients’ ages were 27-51 with a mean age of 41.4. They received no hormones and PG synthetase inhibitors in the cycle preceding operation. Written informed consent was obtained from all patients. Patients were divided into three groups with severe, mild and non dysmenorrhea according to the grade of complaint. Severely dysmenorrheic women required both analgesics and bed rest, while mild dysmenorrheic patients needed only analgesics. Endometrium was classified as menstrual, proliferative and secretory phases by endometrial histology (11). Methods The uterus was opened immediately after extirpation, and myometrium of uterus and ovarian tissue were carefully removed and placed in O.lM Tris
Date received 9 September 1991 Date accepted 13 November 1991 133
134
Prostaglandins Leukotrienes and Essential Fatty Acids
HCl buffer at 4°C. Samples were sliced about 0.2 mm thick and wet weight was 100 mg. Specimens were incubated in O.lM Tris HCl buffer (pH 7.4, 37°C). Incubation medium was changed after the first 15 min to eliminate traumainduced release of PGs, then incubation was continued in fresh medium for 30 min. Medium was replaced every 30 min for 2 h. After incubation, medium was centrifuged at 500 X g for 10 min. The supematant was frozen at -20°C until assay. 6-KetoPGF1,, TXB2, PGFZ, and PGE2 in the supematant were measured by direct RIA. Prostaglandin production was highest in the first 30 min, decreasing gradually according to incubation time in vitro. PG production was shown by the value in the first 30 min and expressed as pg/mg wet weight/30 min. The assay sensitivity was 2 pg, and intra- and interassay coefficients of variation for 6keto-PGFi, were respectively 7.2% and 9.8%, for TXB2 8.5% and 10.3%, for PGFz~ 6.6% and 8.8%, and for PGE2 5.9% and 7.4% (n = 18 and 20 for each PG).
6 - keto PGF,.
TXB, P< 0.05
p < 0.005 r&g
PS/W 1. *. 130 nl”
1. *. no .I”
pglm8 1. *.I30
PGEz
PGF,.
lin
w/w
1. . . I30 nnn NS
NS
1.6 1.4 -
I
28
-
1.2 1.0 -
Statistics Statistical t-test.
analysis
was performed
by Student’s
RESULTS Prostaghxndin production in endometrial cyst aud correlation between dysmenorrhea and PG production As shown in Figure 1, PG production by endometrial cysts was higher than that by normal ovary. Especially there were significant differences in 6-keto-PGF$, and TKR;? production between endometrial cyst and normal ovary. Concerning the correlation between degree of dysmenorrhea and PG production of tissue in endometrial cysts, there was a significant’ difference between mild dysmenorrhea and non dysmenorrhea in 6-keto-PGFi, production., I+wever, there was no significant difference between severe dysmenorrhea and mild dysmenorrhea in 6-keto-PGFi, production. (Fig. 2)
0
Normal
ovary
Endometrial
cyst
Fig. 1 Prostaglandin production of tissue in normal ovary and endometrial cyst. (M + SEM)
pg/mg w. w./30 min
ProstaghunIin production in adenomyosis and correlation between dysmenorrhea and PG production As shown in Figure 3, PG production by adenomyosis was higher than that by normal myometrium. There was a significant difference in 6-keto-PGF;, production between adenomyosis and normal myometrium. Figure 4 shows the correlation between the degree of dysmenorrhea and prostaglandin production of tissue in adenomyosis.
Fii. 2 Correlation between degree of dysmenorrhea and 6-keto PGF,, production of tissue in endometrial cyst. (M f SEM)
Role of PGs in Dysmenorrhea 6 - keto ~glna w
I
of Endometriosis
TXB,
PGF, .
130min P < 0.02 5P < 0.02 4pg/mg *
1. I30 nin
h!LL% Menstrual
Proliferative
Menstrual
Secretorv
PdW1.
Menstrual
Proliferative
Normal
0
Fig. 3
Prostaglandin
w.130
Proliferative
Secretory
Proliferative
Secretorv
NS
ml”
Secretorv
Menstrual
myometrlum
Adenomvosis
production of tissue in normal myometrium and adenomyosis during menstrual cycle. (M + SEM)
pg/mg 1. w. I30 mln D c 0.01 ,
lo-
I
pg/mg w. w. /30 min
. S-
p < 0.05
Pghg w. 1. I30 Rl” .
8.
12 5 4 -
5 I-
I
1
0
11
p < 0.005 I
1
3 2 l-
6 pglmg
w. I30
1.
lin
4 p < 0.02 .3
t
-
Ff. 4 Correlation between degree of dysmenorrhea prostaglandin production of tissue in adenomyosis. (M f SEM)
and
Fii. 5 Correlation between degree of dysmenorrhea 6-keto-PGF,mB, ratio of tissue in adenomyosis. (M + SEM)
and
135
136
Prostaglandins Leukotrienes
and Essential Fatty Acids
There was a significant difference in 6-keto-PGFr, production between severe dysmenorrhea and non dysmenorrhea. We compared the degree of dysmenorrhea with TXB2, PGF2, and PGEz production of tissue in adenomyosis. There were also significant correlations between severe dysmenorrhea and non dysmenorrhea for three kinds of eicosanoid production (Fig. 4). The relationship between the degree of dysmenorrhea and the 6-keto-PGFr&%& ratio of tissue in adenomyosis was also significant (Fig. 5).
DISCUSSION Human reproductive organs are important sites of PG synthesis. In addition, ectopic endometrium has been shown to produce PGs that may contribute to the pathophysiology of endometriosis and adenomyosis (12, 13). The present study shows that tissues of endometrial cyst and adenomyosis produce higher amounts of PGs than normal ovary and myometrium, particularly significantly higher amounts of 6-keto-PGFi,. Furthermore, there was a direct correlation between the degree of dysmenorrhea and PG production of tissue in endometriosis, particularly in adenomyosis. Chan reported that the severity of dysmenorrhea is better correlated to the ratio of menstrual PGF2, : PGE 2 than to the concentration of menstrual PGFza. Dysmenorrhea may be caused by either an elevated PGFz@ production or a relative deficit of PGE2 (14, 15). Yen reported that the PGF2, levels in the serum of dysmenorrheic patients were 4 times higher than those of normal women (16). It is known that endometrial tissue produces 6-keto-PGF;, and TXBz in vitro (17). The severity of symptoms of endometriosis has not always correlated well with the anatomic extent of the disease. This lack of correlation may be due to variations in the metabolic activity of endometriotic implants present at different stages of the disease (12). Vernon speculated that lesions producing large amounts of PG were ‘early’ implants with increased numbers of functional glands present (12). ‘Early’ implants may be pathologically more influential than ‘older’ implants. In this study, there were significant differences in 6-keto-PGI$,, TXB;!, PGF2, and PGE2 production between severe dysmenorrhea and non dysmenorrhea. It is possible to speculate from this study that ‘early’ implants cause severe dysmenorrhea and ‘older’ implants cause mild or no dysmenorrhea. Accordingly, tissue of adenomyosis with severe dysmenorrhea produces larger amounts of PGs. It has been reported that both local and circulating hormones interfere with smooth muscle tonus of
the uterine artery. It has also been concluded that uterine blood flow may be regulated not only by myometrial effects for example of PGs and catecholamines, but also by the action these substances exert on the uterine vascular bed itself. There seems to be a balancing action between PG12 and vasoconstricting compounds such as PGE2 and/or PGFz~. A disturbance of this mechanism may well be a hitherto unknown pathophysiological factor in the development of dysmenorrhea (18). PG12 is able to inhibit the spasms induced by PGF2, (19). The present data are in accordance with those of Omini et al (19), which indicate that PGI;! in fact has an inhibitory effect on isolated human myometrium. Wilhelmsson et al found that PG12 has a potent relaxing effect on uterine arteries which suggested that this substance may be involved in the control of uterine hemodynamics (20). This is the first report of a significant direct correlation between dysmenorrheic severity and PG production of tissue in endometriosis. The mechanism of enhanced PGIZ production in relation to dysmenorrhea is still unclear, and further study is necessary to elucidate the pathophysiological role of PG12 in endometriosis.
Acknowledgements The authors would like to thank ON0 Pharmaceutical Co Ltd, Osaka, Japan, for a generous supply of authentic prostaglandins and antisera.
References 1. Dawood M Y. Dysmenorrhea. Clin Obstet Gynecol 26: 719-727,1983 2. Ylikorkala 0, Dawood M Y. New concepts in dysmenorrhea. Am J Obstet Gynecol 130: 833-847, 1978 3. Rosenwaks Z, Seegar-Jones G. Menstrual pain. Its origins and pathogenesis. S Reprod Med 25: 207, 1980 4. Pickles V R, Hall W J, Best F A, Smith G N. Prostaglandins in endometrium and menstrual fluid from normal and dysmenorrheic subjects. J Obstet Gynecol Br Common W. 72: 185-192, 1965 5. Lundstrom V. Green K. Endoeenous levels of prostaglandin’F*, and its main hetabolites in plasma and endometrium of normal and dysmenorrheic women. Am J Obstet Gynecol 130: 640+X6,1978 6. Chacho K J, Chacho M S, Andersen P J, Scommegna A. Peritoneal fluid in patients with and without endometriosis: Prostanoids and macrophages and their effects on the spermatozoa penetration assay. Am J Obstet gynecol 154: 1290-1299,1986 7. Stevenson C S, Camnbell C G. The svmntoms. physical findings, and clinical diagnosis of pelvic endometriosis. Clin Obstet Gvnecol 3: 441-445. 1960 8. Lumsden M A, Kelly R W, Baird D T. Primary dysmenorrhoea: The importance of both prostaglandin E, and F& Br J Obstet Gynaecol 90: 1135-1140,1983
Role of PGs in Dysmenorrhea 9. Schwartz A, Zor U, Lindner H R, Naor S. Primary
10.
11. 12.
13.
14.
15.
dysmenorrhoea. Alleviation by an inhibitor of prostaghmdin synthesis and action. Obstet Gynecol 44: 709-712,1974 Burns W N, Schenken R S. Pathophysiology. In: Schenken R S fEdsI Endometriosis. Contemoorarv concepts in clinical ‘management. Philadelphia: J B Lippincott Co. pp 89, 1989 Noyes R W, He& A I, Pock J. Dating the endometrial bioosv. Fertil Steril 1: 3-25. 1950 Vernon M W, Beard J S, Graves K, Wilson E A. Classification of endometriotic implants by morphologic appearance and capacity to synthesize urostaelandin F. Fertil Steril46: 801-806. 1986 Drake-T S, O’Brien W F, RamweIl P W; Metx S A. Peritoneal fluid thromboxane B, and 6-keto-prostaglandin F,, in endometribsis. Am J Obstet Gvnecol140: 401-404. 1981 Chan W Y. Prostaglandins and non-steroidal anti-inflammatory drugs in dysmenorrhea. Annu Rev Pharmacol Toxicol23: 131-149, 1983 Bygdeman M, Bremme K, Gillespie A, Lundstrom V. Effects of the prostaglandins on the uterus.
16.
17.
18.
19.
20.
of Endometriosis
Prostaglandins and uterine contractility. Acta Obstet Gynecol Stand Suppl87: 33-38, 1979 Yen S S C. The human menstrual cycle. In: Yen S S C and Jaffe R B, Eds. Reproductive endocrinology, 2nd edn. Philadelphia: W B Saunders, 126-151, 1986 Ylikorkala 0, Viinikka L. Prostaglandins and endometriosis. Acta Obstet Gynecol Stand Suppl 113: 105-107,1983 Wilhelmsson L, Lindblom B, Wikland M, Hamberaer L. Norstrom A. Wiavist N. PGI, mav play a rgle in’the pathophysiology of L ’ dysmenorrhea. Acta Obstet Gynecol Stand Suppl, 113: 69-70, 1983 Omini C, Pasargikhan R, Folco G C, Fano M, Berti F. Pharmacological activity of PGI, and its metabolite 6-oxo-PGF,, on human uterus and fallopian tubes. ProstagIandins 15: 1045-1053, 1978 Wilhelmsson L. Wikland M. Wiavist N. PGH,. TXA, and PGI, have potent and differentiated actions on human uterine contractility. Prostaglandins 21: 277-286, 1981
137