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Mumps Oophoritis: A Cause of Premature Menopause*
Vol.
FERTILITY AND STERILITY Copyright " 1975 The American Fertility Society
26, No.7, July 1975 Printed in U.S A.
MUMPS OOPHORITIS: A CAUSE OF PREMATURE MENOPAUSE* JOHN C. MORRISON, M.D., JAMES R. GIVENS, M.D., WINFRED L. WISER, M.D., F.A.C.O.G., STEWART A. FISH, M.D., F.A.C.O.G.
AND
Division of Reproductive Medicine, Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Memphis, Tennessee 38163
During the evaluation of patients with secondary amenorrhea, the diagnosis of premature menopause is frequently entertained but rarely proven. The classification of premature menopause should be reserved for women with oligomenorrhea under 40 years of age who have evidence of diminished estrogen production and consistently elevated gonadotropins. These criteria would eliminate pituitary failure and most adrenal disorders as the etiology of the menstrual dysfunction. This condition can be referred to as primary ovarian failure, but rarely it may be secondary to the inhibitory factors from other organs that are di:seased. Certainly, surgical castration or ablation of ovarian tissue by radiation or chemical agents 1 is a well recognized cause of premature menopause. Less common etiologies are those associated with polycystic ovaries, 2 ovarian neoplasms, 3· 4 hyperthecosis, 5 autoimmune disease, 6 • 7 adrenal disorders, 8 dysgenetic ovaries, 9 pituitary dysfunction, 10 and psychogenic problems.U- 13 Several types of gonadal infections have been incriminated in primary ovarian failure during the last century, but mumps oophoritis is usually overlooked. This rare cause of premature menopause was first described by ComReceived June 6, 1974. *Supported by Grant RR-211 from the General Clinical Research Center Program at the National Institutes of Health to the University of Tennessee Research Center, where this study was conducted.
by 14 in 1893. It was one of the first suggestions that a gonadal infection might alter reproductive function. The propensity of the mumps virus to affect organ systems other than the salivary glands is well established. 15 These tissues include the brain, thyroid, pancreas, gonads, and mammary gland. Of those who are infected with the causative myxovirus, 20% of the men and 5% of the women have clinically apparent involvement of their gonads. 16 Because the testes are easily examined and observed, the occurrence of mumps orchitis is easily recognized. On the other hand, since the ovaries are reiativeiy inaccessible, the number of reported cases of mumps oophoritis is small. However, in Europe, where it has been most extensively studied, mumps oophoritis is known to occur more commonly than has been diagnosed clinically elsewhere.16'19 The effect of myxovirusinduced oophoritis on menses and on fertility has been studied to different degrees in prepubertal and mature females.17-21 Certainly oophoritis may cause primarly amenorrhea if it affects the prepubertal girl. However, the effect of maternal mumps on the subsequent fertility of the offspring has not been described, although it is known that the virus crosses the placenta and is excreted in the urine and vaginal fluids. 20 We have recently observed three patients with oligomenorrhea and infertility associated with mumps.
655
656
MORRISON ET AL.
CASE REPORTS
Patient 1. J. T., a 34-year-old white female, nulligravida, was evaluated for infertility. She had experienced oligomenorrhea since menarche, at age 12, and had had one to four scanty menstrual periods per year. Two and six years prior to admission, the patient had undergone dilatation and curettage for hypomenorrhea. The pathologic report revealed a proliferative endometrium with focal areas of hyperplasia on both occasions. The patient had taken conjugated estrogens prior to both operations, but none in the past 2 years. She had been given U.S.P. thyroid for 24 months (3 gm/day) 10 years prior to this admission, with no change in the menstrual aberrations. She did have withdrawal bleeding in response to progesterone, but only if primed with estrogen. Her mother had contracted severe bilateral parotiditis and subsequently developed mumps oophoritis 4 days prior to delivery of the patient. The symptoms (fever and abdominal pain) had persisted for 5 to 7 days after parturition. However, there was no history of any infectious process during our patient's neonatal period. In addition, our patient did not have a history of clinically apparent mumps during her childhood. Since age 25, the patient had had mild vasomotor symptoms and repeated episodes of vaginitis. Physical examination revealed an obese female; she weighed 182 pounds and was 5 feet 4 inches tall. She had normal pubic and axillary hair growth. The thyroid gland was diffusely enlarged. No masses were palpable on abdominal examination, and the chest was clear. Pelvic examination revealed a normal clitoris, an atrophic-appearing vagina, and a nulliparous cervix. The uterus was normal in shape and size. The maturation index was 0-60-40. The skull x-rays, screening multiple analyzer (SMA 12), complete blood count, and urinalysis
July 1975
were within normal limits. The ketosteroid level was 8.9 mg/24 hours, and the ketogenic steroid level was 10.9 mg/24 hours, with a urine volume of 1620 ml. The protein-bound iodine was 5.4 mg/100 ml and the T 3 , T 4 , and radioactive iodine uptake were normal. The luteinizing hormone level was 56 miU/ml and the follicle-stimulating hormone level was 53 miU/ml (both values are considered postmenopausal in this laboratory). The mumps skin test was positive and the mumps antibody titer was 1:64. The uterus sounded anteriorly 2% inches and a D&C revealed an atrophic endometrium. At laparoscopy, the ovaries were atrophic (one-fourth normal size) and appeared sclerotic. Patient 2. M. L., a 55-year-old white female, gravida 2, para 2, was examined because she was the mother of our first patient. She had had normal thelarche and menarche at age 12, and had had regular menstrual function except during her pregnancies at ages 19 and 21. She experienced mumps parotiditis during the 39th week of her second pregnancy. The patient subsequently developed severe abdominal pain and fever (104° F). She delivered the infant (patient 1) on the following day, with minimal difficulty, and no hemorrhage was noted. She recuperated slowly but was asymptomatic at the end of the 1st postpartum week. Following the delivery, she experienced amenorrhea, vasomotor symptoms, and frequent vaginal discharges, none of which had ever occurred before the pregnancy. There was no galactorrhea or evidence of pituitary insufficiency. At age 31 she had been given progesterone, which had not induced vaginal bleeding. At age 34 she was found to have a pelvic mass and underwent a laparotomy. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed, which revealed leiomyomata uteri, atrophic endometrium, and atrophic gonads. The pathologic sections of the
Vol. 26, No. 7
MUMPS OOPHORITIS
ovaries revealed a fibrous stroma with no functioning ovarian tissue; this was said by the pathologist to be consistent with mumps oophoritis. Physical examination revealed an obese female; she weighed 194 pounds and was 5 feet 3 inches tall. The axillary and pubic hair were normal. The abdominal examination, except for the midline scar, was normal. The pelvic examination revealed a normal clitoris and a pink, supple vagina. The cervix and uterus were absent. There were no adnexal masses. The maturation index and gonadotropin levels were not determined, since the patient had been receiving replacement therapy (Premarin, 1.25 mg daily) for several years. The mumps skin test was positive; the mumps antibody titer test was 1:128. Patient 3. S. W., a 38-year-old nulliparous black female, was first seen at the age of34 because of vasomotor complaints and decreased libido. Thelarche and menarche had occurred at ages 10 and 12, respectively, with normal menstruation for 7 months. The patient had had parotiditis with clinical oophoritis at age 13. Since that time, she had been amenorrheic. Menstrual flow could be induced by progesterone administration only after estrogen priming. The patient denied any family history of infertility or menstrual difficulties. Physical examination showed an asthenic female, appearing slightly older than her stated age, with normal hair distribution and female habitus. The thyroid was normal in size and -there were no masses in the abdomen. The pelvic examination revealed a normal clitoris, a marital introitus, and a poorly estrogenized vagina with a maturation index of 4-90-6. The uterus was hypoplastic and slightly retroverted; the ovaries were not palpable. The laboratory data showed normal protein-bound iodine, T 3 , and radioactive iodine uptake tests. The 17ketosteroid level was 10.2 mg/24 hours
657
and the 17-ketogenic steroid level was 13.9 mg/24 hours. The skull films were normal, as were the visual fields. The luteinizing hormone level was 96 miU/ml and the follicle-stimulating hormone level 61 miU/ml. The mumps skin test was positive; the antibody titer was 1:64. The patient had not received estrogen therapy for 4 years prior to the clinic visit. She refused admission for laparoscopy and ovarian biopsy. DISCUSSION
The etiology of premature menopause that follows mumps oophoritis is not clear. Several studies have indicated that it may be related to the disturbance of follicular function and possibly of estrogen synthesis. 15 • 18 In one study, 15 82.6% of 150 infertile patients had a history of mumps, whereas only 55.3% of 150 pregnant women had the same history. Most of the infertile patients had had the infection between 7 and 12 years of age, when the ovary is initiating its function. Both of these reports 15 • 18 deal with clinical mumps oophoritis in children, during puberty, and in later life, but do not mention primary ovarian failure resulting from fetal or neonatal infections. As far as we can determine, there is no reference to this in the literature. Our first patient apparently contracted the mumps virus transplacentally during and before parturition. Her ovaries appear to have been affected shortly after birth. It could be promulgated that the lack of immunologic competence in the newborn period could account for the development of mumps oophoritis in the patient without severe clinical symptoms. This proposal is supported by Prinz and Taubert, 15 who stated that the ovaries before puberty appear to be more susceptible to infection. While it is true that the patient did not have a clinically apparent illness at birth, the lack of protection
658
July 1975
MORRISON ET AL.
usually provided by the mother's antibodies may have enabled subclinical neonatal oophoritis to affect her reproductive function severely. The patient's increased antibody titer and positive mumps skin test indicated that she had been exposed to the myxovirus. The patient's negative history of mumps supports our theory of perinatal infection. Of course, many people who are infected by the mumps virus and subsequently develop positive antibody titers lack clinical symptoms. It is doubtful, however, that a subclinical infection would have so severely affected her reproductive function unless it had occurred prior to puberty. In addition, the gross appearance of the ovaries certainly coincided with that described by other authors in cases of mumps oophoritis.19· 21 The second patient is also atypical, since some authors have shown that the fertility of women postpuberty is only rarely affected by mumps oophoritis. 17 It is possible, however, that the hormonal and immunologic changes that take place during pregnancy may alter the susceptibility of the gonad to the myxovirus. Although this supposition could not be supported by a search of the literature, it remains an attractive explanation. As in both patients 1 and 2, there is usually a derangement in the pituitary and/or hypothalamus which results in decreased gonadotropins and often in other abnormalities of pituitary production. The time of infection of our third patient agrees more closely with that reported in the existing literature. Two large studies have shown that the age at which one is affected may influence subsequent fertility.15· 18 In these series, an increased incidence of infertility was seen among women who had been infected during puberty. During this sensitive period, even subclinical cases of mumps oophoritis may affect the gonads. Therefore, it would appear from these three cases that primary ovarian failure,
due to gonadal infection by the mumps virus, can occur any time during life, although it is usually most prevalent at puberty. In addition, it is not necessarily related to the severity of the infection. It is also important to point out that mumps oophoritis, since it is difficult to detect clinically, may be a much more frequent cause of premature menopause than is generally suspected. The use of progesterone withdrawal, maturation index, serum gonadotropins, mumps antibody titer, and, most important, a high index of suspicion is recommended for the diagnosis.
SUMMARY
One cause of secondary oligomenorrhea is ovarian infection. A rare type of infection related to the disturbance of menstrual function is mumps oophoritis. Three patients with premature menopause presumably caused by this agent were described. In one patient the symptoms coincided with a subclinical infection during the perinatal period, with subsequent infertility. Another patient seemed to have had a clinically mild oophoritis during the pubertal period, and the third patient became symptomatic following parturition. It appears that this aberration in menstrual function and fertility may be related to the time during which the infection occurs as well as to the severity of the infection. In addition, it is apparent that mumps oophoritis may be a more frequent cause of premature menopause than has been previously suspected.
REFERENCES 1. Baramki TA, Jones HW: Early premature
menopause. Am J Obstet Gynecol 96:990, 1966 2. Goldzieher JW, Axelrod LR: Clinical and bio· chemical features of polycystic ovarian disease. Fertil Steril 14:631, 1963
Vol. 26, No.7
MUMPS OOPHORITIS
659
3. Pedowitz P, O'Brien FB: Arrhenoblastoma of the 12. Johansson AW, Persson DF, Gamzell BF: Luteal insufficiency and pelvic adhesions. Acta Obstet ovary: review of the literature and report of Gynecol Scand 50:61, 1971 two cases. Obstet Gynecol16:62, 1960 4. Scully RE: Gonadoblastoma, a gonadal tumor 13. Kistner RW: Gynecology, Principles and Practice, Second Edition. Chicago, Year Book related to the dysgerminoma (seminoma) and Medical Publishers, 1964, p 335 capable of sex-hormone production. Cancer 14. Comby J: Localisations des oreillons sur l'ap6:455, 1953 pareil sexuel et ses annexes. Prog Med Paris 5. Shippel S: The ovarian theca cell. Part IV. The 27:115, 1893 hyperthecosis syndrome. J Obstet Gynaecol 15. Prinz W, Taubert HD: Mumps in pubescent feBr Emp 62:321, 1955 males and its effect on later reproductive 6. Blizzard RM, Chee D, Davis W: The incidence function. Gynaecologia 167:23, 1969 of parathyroid and other antibodies in the sera of patients with idiopathic hypopara- 16. Wesselhoeft C, Banks HD: Modem Practice in Infection Fevers. New York, Roeber, 1951 thyroidism. Clin Exp lmmunol 1:119, 1966 7. Irvine WJ: Premature menopause in auto- 17. Seitz L, Americh A: Biologie und Pathologie des Weibes ein Handbuch, Vol VI. Munich, immune diseases. Lancet 1:264, 1969 Urban and Schwarzenburg, 1954 8. Plotz CM, Knowlton AI, Ragan C: The natural history of Cushing's syndrome. Am J Med 18. Trebicka-Kwiatkowska B, Bokiniec M, Borowicz C: Nagminne Zapalenie Przyusznic a 13:587' 1952 Rocrodccosc u Kobiet. Ginecol Pol 35:845, 1964 9. Williams RH: Endocrinology, Fourth Edition. Philadelphia, W B Saunders Co, 1968, p 569 19. Bosch H: Mumps und eveililiches Genitale. 10. Israel SL: Diagnosis and Treatment of MenMonatsschr Geburtsh Gynaekol 104:99, 1936 strual Disorders and Sterility, Fifth Edition. 20. Horsfall FL, Tamm 1: Viral and Rickettsial New York, Roeber Medical Division, Harper Infections of Man, Fourth Edition. Philadeland Row, 1967, p 228 phia, J B Lippincott, 1965, p 339 11. William RH: Endocrinology, Fourth Edition. 21. Brooks H: The involvement of the ovary in Philadelphia, W B Saunders Co, 1968, p 489 epidemic parotitis. JAMA 60:359, 1913
FERTILITY AND STERILITY Copyright " 1975 The American Fertility Society
26, No.7, July 1975 Printed in U.S A.
MUMPS OOPHORITIS: A CAUSE OF PREMATURE MENOPAUSE* JOHN C. MORRISON, M.D., JAMES R. GIVENS, M.D., WINFRED L. WISER, M.D., F.A.C.O.G., STEWART A. FISH, M.D., F.A.C.O.G.
AND
Division of Reproductive Medicine, Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Memphis, Tennessee 38163
During the evaluation of patients with secondary amenorrhea, the diagnosis of premature menopause is frequently entertained but rarely proven. The classification of premature menopause should be reserved for women with oligomenorrhea under 40 years of age who have evidence of diminished estrogen production and consistently elevated gonadotropins. These criteria would eliminate pituitary failure and most adrenal disorders as the etiology of the menstrual dysfunction. This condition can be referred to as primary ovarian failure, but rarely it may be secondary to the inhibitory factors from other organs that are di:seased. Certainly, surgical castration or ablation of ovarian tissue by radiation or chemical agents 1 is a well recognized cause of premature menopause. Less common etiologies are those associated with polycystic ovaries, 2 ovarian neoplasms, 3· 4 hyperthecosis, 5 autoimmune disease, 6 • 7 adrenal disorders, 8 dysgenetic ovaries, 9 pituitary dysfunction, 10 and psychogenic problems.U- 13 Several types of gonadal infections have been incriminated in primary ovarian failure during the last century, but mumps oophoritis is usually overlooked. This rare cause of premature menopause was first described by ComReceived June 6, 1974. *Supported by Grant RR-211 from the General Clinical Research Center Program at the National Institutes of Health to the University of Tennessee Research Center, where this study was conducted.
by 14 in 1893. It was one of the first suggestions that a gonadal infection might alter reproductive function. The propensity of the mumps virus to affect organ systems other than the salivary glands is well established. 15 These tissues include the brain, thyroid, pancreas, gonads, and mammary gland. Of those who are infected with the causative myxovirus, 20% of the men and 5% of the women have clinically apparent involvement of their gonads. 16 Because the testes are easily examined and observed, the occurrence of mumps orchitis is easily recognized. On the other hand, since the ovaries are reiativeiy inaccessible, the number of reported cases of mumps oophoritis is small. However, in Europe, where it has been most extensively studied, mumps oophoritis is known to occur more commonly than has been diagnosed clinically elsewhere.16'19 The effect of myxovirusinduced oophoritis on menses and on fertility has been studied to different degrees in prepubertal and mature females.17-21 Certainly oophoritis may cause primarly amenorrhea if it affects the prepubertal girl. However, the effect of maternal mumps on the subsequent fertility of the offspring has not been described, although it is known that the virus crosses the placenta and is excreted in the urine and vaginal fluids. 20 We have recently observed three patients with oligomenorrhea and infertility associated with mumps.
655
656
MORRISON ET AL.
CASE REPORTS
Patient 1. J. T., a 34-year-old white female, nulligravida, was evaluated for infertility. She had experienced oligomenorrhea since menarche, at age 12, and had had one to four scanty menstrual periods per year. Two and six years prior to admission, the patient had undergone dilatation and curettage for hypomenorrhea. The pathologic report revealed a proliferative endometrium with focal areas of hyperplasia on both occasions. The patient had taken conjugated estrogens prior to both operations, but none in the past 2 years. She had been given U.S.P. thyroid for 24 months (3 gm/day) 10 years prior to this admission, with no change in the menstrual aberrations. She did have withdrawal bleeding in response to progesterone, but only if primed with estrogen. Her mother had contracted severe bilateral parotiditis and subsequently developed mumps oophoritis 4 days prior to delivery of the patient. The symptoms (fever and abdominal pain) had persisted for 5 to 7 days after parturition. However, there was no history of any infectious process during our patient's neonatal period. In addition, our patient did not have a history of clinically apparent mumps during her childhood. Since age 25, the patient had had mild vasomotor symptoms and repeated episodes of vaginitis. Physical examination revealed an obese female; she weighed 182 pounds and was 5 feet 4 inches tall. She had normal pubic and axillary hair growth. The thyroid gland was diffusely enlarged. No masses were palpable on abdominal examination, and the chest was clear. Pelvic examination revealed a normal clitoris, an atrophic-appearing vagina, and a nulliparous cervix. The uterus was normal in shape and size. The maturation index was 0-60-40. The skull x-rays, screening multiple analyzer (SMA 12), complete blood count, and urinalysis
July 1975
were within normal limits. The ketosteroid level was 8.9 mg/24 hours, and the ketogenic steroid level was 10.9 mg/24 hours, with a urine volume of 1620 ml. The protein-bound iodine was 5.4 mg/100 ml and the T 3 , T 4 , and radioactive iodine uptake were normal. The luteinizing hormone level was 56 miU/ml and the follicle-stimulating hormone level was 53 miU/ml (both values are considered postmenopausal in this laboratory). The mumps skin test was positive and the mumps antibody titer was 1:64. The uterus sounded anteriorly 2% inches and a D&C revealed an atrophic endometrium. At laparoscopy, the ovaries were atrophic (one-fourth normal size) and appeared sclerotic. Patient 2. M. L., a 55-year-old white female, gravida 2, para 2, was examined because she was the mother of our first patient. She had had normal thelarche and menarche at age 12, and had had regular menstrual function except during her pregnancies at ages 19 and 21. She experienced mumps parotiditis during the 39th week of her second pregnancy. The patient subsequently developed severe abdominal pain and fever (104° F). She delivered the infant (patient 1) on the following day, with minimal difficulty, and no hemorrhage was noted. She recuperated slowly but was asymptomatic at the end of the 1st postpartum week. Following the delivery, she experienced amenorrhea, vasomotor symptoms, and frequent vaginal discharges, none of which had ever occurred before the pregnancy. There was no galactorrhea or evidence of pituitary insufficiency. At age 31 she had been given progesterone, which had not induced vaginal bleeding. At age 34 she was found to have a pelvic mass and underwent a laparotomy. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed, which revealed leiomyomata uteri, atrophic endometrium, and atrophic gonads. The pathologic sections of the
Vol. 26, No. 7
MUMPS OOPHORITIS
ovaries revealed a fibrous stroma with no functioning ovarian tissue; this was said by the pathologist to be consistent with mumps oophoritis. Physical examination revealed an obese female; she weighed 194 pounds and was 5 feet 3 inches tall. The axillary and pubic hair were normal. The abdominal examination, except for the midline scar, was normal. The pelvic examination revealed a normal clitoris and a pink, supple vagina. The cervix and uterus were absent. There were no adnexal masses. The maturation index and gonadotropin levels were not determined, since the patient had been receiving replacement therapy (Premarin, 1.25 mg daily) for several years. The mumps skin test was positive; the mumps antibody titer test was 1:128. Patient 3. S. W., a 38-year-old nulliparous black female, was first seen at the age of34 because of vasomotor complaints and decreased libido. Thelarche and menarche had occurred at ages 10 and 12, respectively, with normal menstruation for 7 months. The patient had had parotiditis with clinical oophoritis at age 13. Since that time, she had been amenorrheic. Menstrual flow could be induced by progesterone administration only after estrogen priming. The patient denied any family history of infertility or menstrual difficulties. Physical examination showed an asthenic female, appearing slightly older than her stated age, with normal hair distribution and female habitus. The thyroid was normal in size and -there were no masses in the abdomen. The pelvic examination revealed a normal clitoris, a marital introitus, and a poorly estrogenized vagina with a maturation index of 4-90-6. The uterus was hypoplastic and slightly retroverted; the ovaries were not palpable. The laboratory data showed normal protein-bound iodine, T 3 , and radioactive iodine uptake tests. The 17ketosteroid level was 10.2 mg/24 hours
657
and the 17-ketogenic steroid level was 13.9 mg/24 hours. The skull films were normal, as were the visual fields. The luteinizing hormone level was 96 miU/ml and the follicle-stimulating hormone level 61 miU/ml. The mumps skin test was positive; the antibody titer was 1:64. The patient had not received estrogen therapy for 4 years prior to the clinic visit. She refused admission for laparoscopy and ovarian biopsy. DISCUSSION
The etiology of premature menopause that follows mumps oophoritis is not clear. Several studies have indicated that it may be related to the disturbance of follicular function and possibly of estrogen synthesis. 15 • 18 In one study, 15 82.6% of 150 infertile patients had a history of mumps, whereas only 55.3% of 150 pregnant women had the same history. Most of the infertile patients had had the infection between 7 and 12 years of age, when the ovary is initiating its function. Both of these reports 15 • 18 deal with clinical mumps oophoritis in children, during puberty, and in later life, but do not mention primary ovarian failure resulting from fetal or neonatal infections. As far as we can determine, there is no reference to this in the literature. Our first patient apparently contracted the mumps virus transplacentally during and before parturition. Her ovaries appear to have been affected shortly after birth. It could be promulgated that the lack of immunologic competence in the newborn period could account for the development of mumps oophoritis in the patient without severe clinical symptoms. This proposal is supported by Prinz and Taubert, 15 who stated that the ovaries before puberty appear to be more susceptible to infection. While it is true that the patient did not have a clinically apparent illness at birth, the lack of protection
658
July 1975
MORRISON ET AL.
usually provided by the mother's antibodies may have enabled subclinical neonatal oophoritis to affect her reproductive function severely. The patient's increased antibody titer and positive mumps skin test indicated that she had been exposed to the myxovirus. The patient's negative history of mumps supports our theory of perinatal infection. Of course, many people who are infected by the mumps virus and subsequently develop positive antibody titers lack clinical symptoms. It is doubtful, however, that a subclinical infection would have so severely affected her reproductive function unless it had occurred prior to puberty. In addition, the gross appearance of the ovaries certainly coincided with that described by other authors in cases of mumps oophoritis.19· 21 The second patient is also atypical, since some authors have shown that the fertility of women postpuberty is only rarely affected by mumps oophoritis. 17 It is possible, however, that the hormonal and immunologic changes that take place during pregnancy may alter the susceptibility of the gonad to the myxovirus. Although this supposition could not be supported by a search of the literature, it remains an attractive explanation. As in both patients 1 and 2, there is usually a derangement in the pituitary and/or hypothalamus which results in decreased gonadotropins and often in other abnormalities of pituitary production. The time of infection of our third patient agrees more closely with that reported in the existing literature. Two large studies have shown that the age at which one is affected may influence subsequent fertility.15· 18 In these series, an increased incidence of infertility was seen among women who had been infected during puberty. During this sensitive period, even subclinical cases of mumps oophoritis may affect the gonads. Therefore, it would appear from these three cases that primary ovarian failure,
due to gonadal infection by the mumps virus, can occur any time during life, although it is usually most prevalent at puberty. In addition, it is not necessarily related to the severity of the infection. It is also important to point out that mumps oophoritis, since it is difficult to detect clinically, may be a much more frequent cause of premature menopause than is generally suspected. The use of progesterone withdrawal, maturation index, serum gonadotropins, mumps antibody titer, and, most important, a high index of suspicion is recommended for the diagnosis.
SUMMARY
One cause of secondary oligomenorrhea is ovarian infection. A rare type of infection related to the disturbance of menstrual function is mumps oophoritis. Three patients with premature menopause presumably caused by this agent were described. In one patient the symptoms coincided with a subclinical infection during the perinatal period, with subsequent infertility. Another patient seemed to have had a clinically mild oophoritis during the pubertal period, and the third patient became symptomatic following parturition. It appears that this aberration in menstrual function and fertility may be related to the time during which the infection occurs as well as to the severity of the infection. In addition, it is apparent that mumps oophoritis may be a more frequent cause of premature menopause than has been previously suspected.
REFERENCES 1. Baramki TA, Jones HW: Early premature
menopause. Am J Obstet Gynecol 96:990, 1966 2. Goldzieher JW, Axelrod LR: Clinical and bio· chemical features of polycystic ovarian disease. Fertil Steril 14:631, 1963
Vol. 26, No.7
MUMPS OOPHORITIS
659
3. Pedowitz P, O'Brien FB: Arrhenoblastoma of the 12. Johansson AW, Persson DF, Gamzell BF: Luteal insufficiency and pelvic adhesions. Acta Obstet ovary: review of the literature and report of Gynecol Scand 50:61, 1971 two cases. Obstet Gynecol16:62, 1960 4. Scully RE: Gonadoblastoma, a gonadal tumor 13. Kistner RW: Gynecology, Principles and Practice, Second Edition. Chicago, Year Book related to the dysgerminoma (seminoma) and Medical Publishers, 1964, p 335 capable of sex-hormone production. Cancer 14. Comby J: Localisations des oreillons sur l'ap6:455, 1953 pareil sexuel et ses annexes. Prog Med Paris 5. Shippel S: The ovarian theca cell. Part IV. The 27:115, 1893 hyperthecosis syndrome. J Obstet Gynaecol 15. Prinz W, Taubert HD: Mumps in pubescent feBr Emp 62:321, 1955 males and its effect on later reproductive 6. Blizzard RM, Chee D, Davis W: The incidence function. Gynaecologia 167:23, 1969 of parathyroid and other antibodies in the sera of patients with idiopathic hypopara- 16. Wesselhoeft C, Banks HD: Modem Practice in Infection Fevers. New York, Roeber, 1951 thyroidism. Clin Exp lmmunol 1:119, 1966 7. Irvine WJ: Premature menopause in auto- 17. Seitz L, Americh A: Biologie und Pathologie des Weibes ein Handbuch, Vol VI. Munich, immune diseases. Lancet 1:264, 1969 Urban and Schwarzenburg, 1954 8. Plotz CM, Knowlton AI, Ragan C: The natural history of Cushing's syndrome. Am J Med 18. Trebicka-Kwiatkowska B, Bokiniec M, Borowicz C: Nagminne Zapalenie Przyusznic a 13:587' 1952 Rocrodccosc u Kobiet. Ginecol Pol 35:845, 1964 9. Williams RH: Endocrinology, Fourth Edition. Philadelphia, W B Saunders Co, 1968, p 569 19. Bosch H: Mumps und eveililiches Genitale. 10. Israel SL: Diagnosis and Treatment of MenMonatsschr Geburtsh Gynaekol 104:99, 1936 strual Disorders and Sterility, Fifth Edition. 20. Horsfall FL, Tamm 1: Viral and Rickettsial New York, Roeber Medical Division, Harper Infections of Man, Fourth Edition. Philadeland Row, 1967, p 228 phia, J B Lippincott, 1965, p 339 11. William RH: Endocrinology, Fourth Edition. 21. Brooks H: The involvement of the ovary in Philadelphia, W B Saunders Co, 1968, p 489 epidemic parotitis. JAMA 60:359, 1913