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Menstruation and fertility in anorexia nervosa
Menstruation and fertitity in anorexia nervosa THOMAS
A.
RAYMOND Rochester,
STARKEY, A.
LEE,
M.D. M.D.
Minnesota
Follow-up information with regard to menstruation and fertility was obtained for 58 patients with anorexia nervosa who were examined during the years 1955 to 1959. All patients had an established menstrual pattern prior to the onset of disease, but most became amenorrheic concurrent with the anorexia neruosa. Most reported improvement in their condition (that is, weight gain); all but three of the improved patients experienced menstrual return, and of those who attempted firegnancy, only one failed. In the group reporting no improvement, none experienced menstrual return, and none conceived. Two factors are of prognostic significance for recovery from anorexia nervosa, and hence for return of menstruation and fertility: weight loss of less than 30 per cent and the onset of anorexia nervosa prior to the age of 23 years; both factors were associated with a good prognosis.
“A Y o u N c woman thus afflicted, her clothes scarcely hanging together on her anatomy, her pulse slow and slack, her temperature two degrees below the normal mean, her bowels closed, her hair like that of a corpse dry and lustreless, her face and limbs ashy and cold, her hollow eyes the only vivid thing about her. . . .“I This description, written by Sir Clifford Allbutt in 1908, vividly brings to mind the disease called anorexia nervosa. A generally acceptable definition of this sometimes confused entity was offered by John Berkman,2-5 who has written extensively on the subject. He described the disease as a symptom complex of mental, physical, and physiologic changes exhibited
by persons who starve because of anorexia or aversion to food; these symptoms are the result of underlying psychic and emotional disturbances. The Englishman Sir William Withie GulP and the Frenchman Charles Las&que14 are generally credited with introducing the condition into modern medical writing. Both described anorexia nervosa in 1873, referring to the condition as hysterical anorexia. From 1914 through 1918, Morris Simmonds,20-22 a pathologist at the University of Hamburg, published several cases of clinically and pathologically correlated anterior pituitary insufficiency in man. Cachexia was a prominent feature in his reports, and he stated that it most often resulted from postpartum embolic necrosis of the anterior lobe of the pituitary gland, but that it might also result from a baaophilic adenoma or a tuberculous process of the pituitary gland. As the result
From the Mayo Clinic and Mayo Foundation: Section of Obstetrics and Gynecology and Mayo Graduate School of Medicine (University of Minnesota), Rochester.
374
Volume Number
105 3
of an erroneous emphasis on loss of weight by Simmonds and subsequent writers, the entity ,of organic pituitary insufficiency (Simmonds’ disease) and anorexia nervosa (functional pituitary insufficiency) became closely associated in medical thinking and writing during the next 2j/2 decades. An unfortunate result was the reporting of many cases of so-called Simmonds’ disease, which in retrospect were most probably anorexia nervosa.gl l5 In 1938 SheeharP* lg described the clinical syndrome that bears his name: failure of lactation, continuing amenorrhea, and increased sensitivity to cold in some women who had survived massive postpartum hemorrhage. He attributed these symptoms to anterior pituitary necrosis but noted that cachexia was usually not part of the syndrome. As a result of these observations, cachexia was largely eliminated as a necessary feature of anterior pituitary failure. There has been a large accumulation of literature during the past 30 years on the clinical, laboratory, and psychiatric aspects of anorexia nervosa. Few articles, however, have discussed specifically the menstrual or subsequent fertility characteristics of the women so afflicted. Metabolic studies are even rarer; estrogen and gonadotropin excretions recently have been studied in England, though, and will be commented on later. In 1953, KayI reported on 38 patients who had anorexia nervosa; follow-up information was obtained for 24 of the 34 women. He found that, in general, women who regained normal weight recovered menstrual function spontaneously; normal menses and reproductive ability could return even after many years of amenorrhea. He considered only 4 patients to have fully recovered; that is, they had normal menses and had produced children. Eleven patients experienced somewhat disturbed menses, 4 had grossly irregular menses, and 5 remained amenorrheic. DeCarle* in 1962 reported a case of anorexia nervosa in which conception and normal pregnancy occurred during the disease. His patient weighed 65 pounds at the time of
Menstruation
and fertility
in anorexia
nervosa
375
conception; treatment included a high protein diet and psychotherapy. At the end of an uneventful prenatal course (40 weeks), she weighed 100 pounds; delivery of a mature infant was accomplished without difficulty. In 1964 Bernstein0 reported on a young woman treated with psychotherapy and electroshock therapy for two episodes of anorexia nervosa within 1 year. She was amenorrheic for approximately 3 years before the initiation of treatment, and remained so until some months after the second episode. Her menses returned then after cessation of electroshock therapy, several months after normal weight had been regained. She married and conceived without difficulty shortly afterward. Farquharson and HylandlO reported in 1966 on 15 patients who were treated for anorexia nervosa. Twelve of the patients were females, 10 of whom were postmenarche and had normally established menses prior to the onset of disease. All became amenorrheic either before or during the time of weight loss, but all regained normal menses after return to normal weight. Seven of the female patients subsequently married, and each produced at least one offspring. Dally and Sargant7 have recently reported on 47 women treated for anorexia nervosa; approximately one-half were given a chlorpromazine and modified insulin regimen, while the “control group” was treated with bed rest but no specific drug therapy. Approximately 70 per cent of each group were experiencing regular menses at the follow-up 3 to 5 years later. Several of the married patients in each group had produced offspring. The authors commented that menses usually returned only when the weight increased to at least 75 per cent of standard and when underlying psychological causes were resolved. Menstrual return was somewhat delayed in the chlorpromazine and insulin group, averaging twice as long as in the “control group.” They summarized by saying: “Most anorexia nervosa patients are backward in their psychosexual development and consequently have considerable conflicts over
376
cktober
Starkey and Lee
Table I. Characteristics of anorexia nervosa -.-____-. -----____. History
~_l_~l____-__-----._
Physical examination
Emotional upset Anorexia Rapid filling Bloating Constipation Amenorrhea Decreased libido
Weight loss Pallor Dry
Low basal metabolic rate Normal protein-bound iodine Normal fasting blood sugar
skin
Lanugo-type hair Cold hands or feet Lack of sweating Normal pubic or axillary
hair
their sexual feelings and behaviour. Nonetheless, these girls are able to marry and have children. . . .” Anorexia nervosa usually affects women who are between 15 and 30 years of age and is only rarely encountered in the male. Because it is primarily an illness of young women, we believe that a review of the Mayo Clinic experience with regard to menstrual and fertility patterns will be of value to the gynecologist. and
material
The diagnosis of anorexia nervosa in the present series was based on the characteristic history, physical examination, and laboratory findings as described by Berkman4 (Table I). The records of 225 consecutive cases were reviewed (1955 to 1959 inclusive), and from these 88 were selected for study. This study group was comprised of women with an established menstrual pattern prior to the onset of their disease, but who had not yet entered the climacteric; excluded were those who had undergone hysterectomy, salpingectomy, or oophorectomy and those in whom the diagnosis of anorexia nervosa was questionable. Follow-up was obtained for approximately two thirds of the study group (58 patients), primarily by a letter of inquiry; in a few cases, follow-up was completed by information on the patient’s chart or by a letter from her personal physician. Findings
Forty-three of the 58 patients showed improvement in their anorexia nervosa, both
-.
Laboratory
Small uterus
Methods
1, I363
Am. J Obst. & Gym.
Flat Low Low Low
glucose
tolerance
curve
gonadotropin levels estrogen level 17-ketosteroid
and
17-hydroxysteroid
levels
Low pregnanediol level
subjectively and by return of appetite and gain in weight. The remaining 15 patients gave little or no evidence of improvement. Since it was not possible to obtain absolutely objective criteria for improvement, our decision on each patient (improved or not improved) was based primarily on the patient’s replies to questions regarding her present general health, her appetite, and her weight, There were two deaths in this series. One patient died of acute ulcerative colitis 11 years after the original diagnosis and treatment at this clinic. She had experienced improvement in her anorexia nervosa and was in fact 4 months pregnant at the time of death. The other patient died 8 years after the original diagnosis of causes unknown to the authors. There had been no improvement reported in her anorexia nervosa. Table II summarizes the information sought in this study. Of 43 patients who subsequently improved, 41 were amenorrheic for various lengths of time before, during, or when in the recovery phase of anorexia nervosa. Seven of these 41 patients noted amenorrhea beginning 1 to 3 years prior to the onset of weight loss, but the majority (34 patients) reported amenorrhea concurrent with weight loss. Regular menses have returned in 38 of the 41 women, at intervals varying from 3 months to several years after the beginning of improvement (that is, weight gain). Although our data on this point are insufficient, it appeared that regular menses usually returned within 1 year after the beginning of weight gain, but frequently not until the patient had virtually regained her original weight, and occasionally not until
Volume Number
105 3
Menstruation
many months after otherwise complete recovery. Hormone therapy, usually in the form of cyclic conjugated estrogens, was given to 41 patients at some time during the course of their illness. There was no apparent correlation between menstrual return and the administration of hormones. Three patients reported improvement of the anorexia nervosa but did not experience the return of menses. However, two of these patients had regained less than half of the weight they had lost; the third patient had regain,ed to her original weight but was lost to follow-up 1 year after improvement began. Thirty-four of our improved patients are now married, and of 28 who have attempted pregnancy, 27 have conceived without difliculty at least once; the 1 patient who has not become pregnant noted the return of menses only 4 months prior to our inquiry, after 8 years of anorexia nervosa and 9 years of amenorrhea. Fifteen patients (26 per cent) reported no improvement in their anorexia nervosa; as mig;ht be expected, all remain amenorrheic. One patient noted the onset of amenorrhea just before the onset of weight loss, but the rest became amenorrheic concurrent with weight loss. Less than half of this group, seven patients, are married, and only one patient has attempted pregnancy (without success). A number of characteristics of the two groups of patients, improved and not improved, are listed in Table III. The average age at menarche was essentially the same in
Amenorrhea Menstrual Married,
return
Pregnancy attempted Pregnancy achieved
26%)
41 38 34 28 27
15 ; 1 0
nervosa
377
Table III. Characteristics of two groups of patients with anorexia nervosa
Averages z; 1ZE;
characteristics of two groups of patients with anorexia nervosa
74%)
in anorexia
each group. The age at onset of anorexia nervosa was somewhat less in patients who eventually improved, averaging 19.2 years; in contrast, the age at onset of disease in the not improved group averaged 22.3 years. The average weight in each group prior to the onset of anorexia nervosa was similar; however, the group destined to remain ill lost significantly more weight. Those who improved gained weight more or less in accordance with their height and build, the average current weight being 116.5 pounds. The majority of improved patients now weigh slightly less than their original weight, and only two weigh more than 140 pounds. In contrast, those who reported no improvement now weigh only a few pounds more than their weight at the initial examination. The relationship between age at onset of disease and prognosis is better illustrated by Fig. 1. The majority (36/45) of patients in whom anorexia nervosa developed prior to the age of 23 years experienced improvement; but only half (6/12) of the women whose illness began after 23 years of age improved (P < 0.05). Fig. 2 ilIustrates the relationship between weight loss and prognosis. Twenty-seven patients lost as much as 30 per cent of their original weight; only one patient did not eventually improve. Thirty-one patients lost more than 30 per cent of their original
Table III. Menstrual and fertility
Improved Not improved patients patients (43 patients, (15 patients,
and fertility
Age Age
at menarche (yr.) at onset of illness (Yr.) Weight before illness (pounds) Weight loss (pounds) Weight at initial examination (pounds) Current weight (pounds) Basal metabolic rate (%)
12.2 19.2 124
12.6 22.3 121
37.6 87.0
49.9 74.0
116.5 -22
78.5 -16
378
Starkey and Lee
~23
onset
and over at prognosis
23
Age and
Fig. I. Relationship between age (years) of disease and prognosis.
31% ond Weight loss and prognosis
<31%
Fig. 2. Relationship and prognosis.
at onset
over
between weight Ioss (per cent)
weight; 17 of this group (P < 0.001).
have
not improved
Comment Management of anorexia nervosa patients through the years has run the full gamut of medical treatment. Early methods included forced fluids, tube feeding or the threat of it, isolation, hospitalization with strict nursing care, massage, electric stimulation, and hydrotherapy. Attempts to treat the emotional aspect have included simple suggestion, discussion, psychotherapy, psychoanalysis, hypnosis, insulin shock, and frontal lobotomy. At one time, each of the following has been in vogue: pituitary extract, implanted calves’ pituitary, adrenocorticotropic hormone, corticosteroids, thyroid extract, estrogen, and insulin. Most of the patients in the present series were evaluated and managed by the same physician on an outpatient basis.ll The program of treatment was basically the same
for all patients: unhurried supportive psychotherapy for from 4 to 6 weeks, during which time a high-protein, high-vitamin diet progressed from about 1,400 calories per day to about 3,600 calories per day. A few patients required hospitalization because of extreme emaciation, and their initial treatment included tube feeding and intravenously administered fluids. Cyclic estrogen therapy was given to some patients who were seen after many months of amenorrhea, in an effort to prime the uterus for the return of menstruation. We believe that there are two factors of prognostic significance for recovery from anorexia nervosa and hence for return of normal menstruation and fertility. These factors are age at onset of anorexia nervosa and percentage of weight lost. It is evident from Fig. 1 that the onset of anorexia nervosa prior to 23 years of age is associated with a good outlook for recovery, but when the illness begins at age 23 years or after, the outlook is only fair. Similarly, a weight loss of as much as 30 per cent of the original weight is associated with an excellent outlook for recovery; whereas a weight loss of more than 30 per cent is associated with only a fair prognosis (Fig. 2) . Menstrual function in anorexia nervosa is not wholly dependent on loss or gain of weight. This is indicated in our study by several patients who became amenorrheic prior to the onset of weight loss and several who remained amenorrheic for some months to years after apparent recovery. Russel and co-workerslGj I7 in England have recently studied estrogen and gonadotropin excretion during refeeding in patients with anorexia nervosa. They observed a persisting absence of cyclic activity, which they believed was a hypothalamic effect and concluded that malnutrition in anorexia nervosa was only partly responsible for menstrual abnormalities. Ccrtain of the clinical characteristics that occur in patients with anorexia nervosa-their refusal of food, weight loss, amenorrhea, and disturbances in water regulation-may be reproduced in the experimental model. Rus-
Menstruation
sell6 postulates “. . . that the anorexia induced by the hypothalamic disturbance engenders the abnormal thinking that commonly occurs--the revulsion for fattening foods and the preoccupation with body weight and body image. In addition, failure of the gonads
and fertility
in anorexia
nervosa
379
would be held responsible for these patients failing to reach full psychosexual maturity.” Thus the hypothalamic disturbance he is postulating must allow for a disorder that may fluctuate over long periods, but from which complete recovery is possible.
REFERENCES
1. Allbutt,
2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
C.: Neuroses of the Stomach and of Other Parts of the Abdomen, in Allbutt, C., and Rolleston, H. D.: System of Medicine, London, 1908, The Macmillan Company, Ltd., vol. III, p. 398. Berkman, J. M.: Am. J. M. SC. 180: 411, 1930. Berkman, J. M.: M. Clin. North America 23: 9OL, 1939. Berkman, J. M.: Ann. Int. Med. 22: 679, 1945. Be:rkman, J. M.: Postgrad. Med. 3: 237, 1948. Bernstein, I. C.: Am. J. Psychiat. 120: 1023, 1964. Dally, P., and Sargant, W.: Brit. M. J. 2: 793, 1966. DeCarle, D. W.: S. Clin. North America 42: 92L, 1962. Escamilla, R. F.: J. Nerv. & Ment. Dis. 99: 583, 1944. Farquharson, R. F., and Hyland, H. H.: Canad. M. A. J. 94: 411, 1966. Gi6in, Mary E., Frazier, S. H., Robinson, D.
12. 13. 14. 15. 16. 17.
18. 19. 20. 21. 22.
B., and Johnson, Adelaide M.: Proc. Staff Meet., Mayo Clin. 32: 171, 1957. Gull, W. W.: Brit. M. J. 2: 527, 1873. Kay, D. W. K.: Proc. Roy. Sot. Med. 46: 669, 1953. Laseque, Cl.: Arch. Gen. Med. 131: 385, 1873. Richardson, H. B.: Arch. Int. Med. (Chicago) 63: 1, 1939. Russel, G. F. M.: Proc. Roy. Sot. Med. 58: 811, 1965. Russel, G. F. M., Loraine, J. A., Bell, E. T., and Harkness, R. A.: J. Psychosom. Res. 9: 79, 1965. Sheehan, H. L.: J. Path. & Bact. 45: 189, 1937. Sheehan, H. L., and Murdoch, R.: J. Obst. Sr Gynaec. Brit. Comm. 45: 456, 1938. Simmonds, M.: Deutsch. Med. Wchnschr. 40: 322, 1914. Simmonds, M.: Deutsch. Med. Wchnschr. 42: 190, 1916. Simmonds, M.: Deutsch. Med. Wchnschr. 44: 852, 1918.
A.
RAYMOND Rochester,
STARKEY, A.
LEE,
M.D. M.D.
Minnesota
Follow-up information with regard to menstruation and fertility was obtained for 58 patients with anorexia nervosa who were examined during the years 1955 to 1959. All patients had an established menstrual pattern prior to the onset of disease, but most became amenorrheic concurrent with the anorexia neruosa. Most reported improvement in their condition (that is, weight gain); all but three of the improved patients experienced menstrual return, and of those who attempted firegnancy, only one failed. In the group reporting no improvement, none experienced menstrual return, and none conceived. Two factors are of prognostic significance for recovery from anorexia nervosa, and hence for return of menstruation and fertility: weight loss of less than 30 per cent and the onset of anorexia nervosa prior to the age of 23 years; both factors were associated with a good prognosis.
“A Y o u N c woman thus afflicted, her clothes scarcely hanging together on her anatomy, her pulse slow and slack, her temperature two degrees below the normal mean, her bowels closed, her hair like that of a corpse dry and lustreless, her face and limbs ashy and cold, her hollow eyes the only vivid thing about her. . . .“I This description, written by Sir Clifford Allbutt in 1908, vividly brings to mind the disease called anorexia nervosa. A generally acceptable definition of this sometimes confused entity was offered by John Berkman,2-5 who has written extensively on the subject. He described the disease as a symptom complex of mental, physical, and physiologic changes exhibited
by persons who starve because of anorexia or aversion to food; these symptoms are the result of underlying psychic and emotional disturbances. The Englishman Sir William Withie GulP and the Frenchman Charles Las&que14 are generally credited with introducing the condition into modern medical writing. Both described anorexia nervosa in 1873, referring to the condition as hysterical anorexia. From 1914 through 1918, Morris Simmonds,20-22 a pathologist at the University of Hamburg, published several cases of clinically and pathologically correlated anterior pituitary insufficiency in man. Cachexia was a prominent feature in his reports, and he stated that it most often resulted from postpartum embolic necrosis of the anterior lobe of the pituitary gland, but that it might also result from a baaophilic adenoma or a tuberculous process of the pituitary gland. As the result
From the Mayo Clinic and Mayo Foundation: Section of Obstetrics and Gynecology and Mayo Graduate School of Medicine (University of Minnesota), Rochester.
374
Volume Number
105 3
of an erroneous emphasis on loss of weight by Simmonds and subsequent writers, the entity ,of organic pituitary insufficiency (Simmonds’ disease) and anorexia nervosa (functional pituitary insufficiency) became closely associated in medical thinking and writing during the next 2j/2 decades. An unfortunate result was the reporting of many cases of so-called Simmonds’ disease, which in retrospect were most probably anorexia nervosa.gl l5 In 1938 SheeharP* lg described the clinical syndrome that bears his name: failure of lactation, continuing amenorrhea, and increased sensitivity to cold in some women who had survived massive postpartum hemorrhage. He attributed these symptoms to anterior pituitary necrosis but noted that cachexia was usually not part of the syndrome. As a result of these observations, cachexia was largely eliminated as a necessary feature of anterior pituitary failure. There has been a large accumulation of literature during the past 30 years on the clinical, laboratory, and psychiatric aspects of anorexia nervosa. Few articles, however, have discussed specifically the menstrual or subsequent fertility characteristics of the women so afflicted. Metabolic studies are even rarer; estrogen and gonadotropin excretions recently have been studied in England, though, and will be commented on later. In 1953, KayI reported on 38 patients who had anorexia nervosa; follow-up information was obtained for 24 of the 34 women. He found that, in general, women who regained normal weight recovered menstrual function spontaneously; normal menses and reproductive ability could return even after many years of amenorrhea. He considered only 4 patients to have fully recovered; that is, they had normal menses and had produced children. Eleven patients experienced somewhat disturbed menses, 4 had grossly irregular menses, and 5 remained amenorrheic. DeCarle* in 1962 reported a case of anorexia nervosa in which conception and normal pregnancy occurred during the disease. His patient weighed 65 pounds at the time of
Menstruation
and fertility
in anorexia
nervosa
375
conception; treatment included a high protein diet and psychotherapy. At the end of an uneventful prenatal course (40 weeks), she weighed 100 pounds; delivery of a mature infant was accomplished without difficulty. In 1964 Bernstein0 reported on a young woman treated with psychotherapy and electroshock therapy for two episodes of anorexia nervosa within 1 year. She was amenorrheic for approximately 3 years before the initiation of treatment, and remained so until some months after the second episode. Her menses returned then after cessation of electroshock therapy, several months after normal weight had been regained. She married and conceived without difficulty shortly afterward. Farquharson and HylandlO reported in 1966 on 15 patients who were treated for anorexia nervosa. Twelve of the patients were females, 10 of whom were postmenarche and had normally established menses prior to the onset of disease. All became amenorrheic either before or during the time of weight loss, but all regained normal menses after return to normal weight. Seven of the female patients subsequently married, and each produced at least one offspring. Dally and Sargant7 have recently reported on 47 women treated for anorexia nervosa; approximately one-half were given a chlorpromazine and modified insulin regimen, while the “control group” was treated with bed rest but no specific drug therapy. Approximately 70 per cent of each group were experiencing regular menses at the follow-up 3 to 5 years later. Several of the married patients in each group had produced offspring. The authors commented that menses usually returned only when the weight increased to at least 75 per cent of standard and when underlying psychological causes were resolved. Menstrual return was somewhat delayed in the chlorpromazine and insulin group, averaging twice as long as in the “control group.” They summarized by saying: “Most anorexia nervosa patients are backward in their psychosexual development and consequently have considerable conflicts over
376
cktober
Starkey and Lee
Table I. Characteristics of anorexia nervosa -.-____-. -----____. History
~_l_~l____-__-----._
Physical examination
Emotional upset Anorexia Rapid filling Bloating Constipation Amenorrhea Decreased libido
Weight loss Pallor Dry
Low basal metabolic rate Normal protein-bound iodine Normal fasting blood sugar
skin
Lanugo-type hair Cold hands or feet Lack of sweating Normal pubic or axillary
hair
their sexual feelings and behaviour. Nonetheless, these girls are able to marry and have children. . . .” Anorexia nervosa usually affects women who are between 15 and 30 years of age and is only rarely encountered in the male. Because it is primarily an illness of young women, we believe that a review of the Mayo Clinic experience with regard to menstrual and fertility patterns will be of value to the gynecologist. and
material
The diagnosis of anorexia nervosa in the present series was based on the characteristic history, physical examination, and laboratory findings as described by Berkman4 (Table I). The records of 225 consecutive cases were reviewed (1955 to 1959 inclusive), and from these 88 were selected for study. This study group was comprised of women with an established menstrual pattern prior to the onset of their disease, but who had not yet entered the climacteric; excluded were those who had undergone hysterectomy, salpingectomy, or oophorectomy and those in whom the diagnosis of anorexia nervosa was questionable. Follow-up was obtained for approximately two thirds of the study group (58 patients), primarily by a letter of inquiry; in a few cases, follow-up was completed by information on the patient’s chart or by a letter from her personal physician. Findings
Forty-three of the 58 patients showed improvement in their anorexia nervosa, both
-.
Laboratory
Small uterus
Methods
1, I363
Am. J Obst. & Gym.
Flat Low Low Low
glucose
tolerance
curve
gonadotropin levels estrogen level 17-ketosteroid
and
17-hydroxysteroid
levels
Low pregnanediol level
subjectively and by return of appetite and gain in weight. The remaining 15 patients gave little or no evidence of improvement. Since it was not possible to obtain absolutely objective criteria for improvement, our decision on each patient (improved or not improved) was based primarily on the patient’s replies to questions regarding her present general health, her appetite, and her weight, There were two deaths in this series. One patient died of acute ulcerative colitis 11 years after the original diagnosis and treatment at this clinic. She had experienced improvement in her anorexia nervosa and was in fact 4 months pregnant at the time of death. The other patient died 8 years after the original diagnosis of causes unknown to the authors. There had been no improvement reported in her anorexia nervosa. Table II summarizes the information sought in this study. Of 43 patients who subsequently improved, 41 were amenorrheic for various lengths of time before, during, or when in the recovery phase of anorexia nervosa. Seven of these 41 patients noted amenorrhea beginning 1 to 3 years prior to the onset of weight loss, but the majority (34 patients) reported amenorrhea concurrent with weight loss. Regular menses have returned in 38 of the 41 women, at intervals varying from 3 months to several years after the beginning of improvement (that is, weight gain). Although our data on this point are insufficient, it appeared that regular menses usually returned within 1 year after the beginning of weight gain, but frequently not until the patient had virtually regained her original weight, and occasionally not until
Volume Number
105 3
Menstruation
many months after otherwise complete recovery. Hormone therapy, usually in the form of cyclic conjugated estrogens, was given to 41 patients at some time during the course of their illness. There was no apparent correlation between menstrual return and the administration of hormones. Three patients reported improvement of the anorexia nervosa but did not experience the return of menses. However, two of these patients had regained less than half of the weight they had lost; the third patient had regain,ed to her original weight but was lost to follow-up 1 year after improvement began. Thirty-four of our improved patients are now married, and of 28 who have attempted pregnancy, 27 have conceived without difliculty at least once; the 1 patient who has not become pregnant noted the return of menses only 4 months prior to our inquiry, after 8 years of anorexia nervosa and 9 years of amenorrhea. Fifteen patients (26 per cent) reported no improvement in their anorexia nervosa; as mig;ht be expected, all remain amenorrheic. One patient noted the onset of amenorrhea just before the onset of weight loss, but the rest became amenorrheic concurrent with weight loss. Less than half of this group, seven patients, are married, and only one patient has attempted pregnancy (without success). A number of characteristics of the two groups of patients, improved and not improved, are listed in Table III. The average age at menarche was essentially the same in
Amenorrhea Menstrual Married,
return
Pregnancy attempted Pregnancy achieved
26%)
41 38 34 28 27
15 ; 1 0
nervosa
377
Table III. Characteristics of two groups of patients with anorexia nervosa
Averages z; 1ZE;
characteristics of two groups of patients with anorexia nervosa
74%)
in anorexia
each group. The age at onset of anorexia nervosa was somewhat less in patients who eventually improved, averaging 19.2 years; in contrast, the age at onset of disease in the not improved group averaged 22.3 years. The average weight in each group prior to the onset of anorexia nervosa was similar; however, the group destined to remain ill lost significantly more weight. Those who improved gained weight more or less in accordance with their height and build, the average current weight being 116.5 pounds. The majority of improved patients now weigh slightly less than their original weight, and only two weigh more than 140 pounds. In contrast, those who reported no improvement now weigh only a few pounds more than their weight at the initial examination. The relationship between age at onset of disease and prognosis is better illustrated by Fig. 1. The majority (36/45) of patients in whom anorexia nervosa developed prior to the age of 23 years experienced improvement; but only half (6/12) of the women whose illness began after 23 years of age improved (P < 0.05). Fig. 2 ilIustrates the relationship between weight loss and prognosis. Twenty-seven patients lost as much as 30 per cent of their original weight; only one patient did not eventually improve. Thirty-one patients lost more than 30 per cent of their original
Table III. Menstrual and fertility
Improved Not improved patients patients (43 patients, (15 patients,
and fertility
Age Age
at menarche (yr.) at onset of illness (Yr.) Weight before illness (pounds) Weight loss (pounds) Weight at initial examination (pounds) Current weight (pounds) Basal metabolic rate (%)
12.2 19.2 124
12.6 22.3 121
37.6 87.0
49.9 74.0
116.5 -22
78.5 -16
378
Starkey and Lee
~23
onset
and over at prognosis
23
Age and
Fig. I. Relationship between age (years) of disease and prognosis.
31% ond Weight loss and prognosis
<31%
Fig. 2. Relationship and prognosis.
at onset
over
between weight Ioss (per cent)
weight; 17 of this group (P < 0.001).
have
not improved
Comment Management of anorexia nervosa patients through the years has run the full gamut of medical treatment. Early methods included forced fluids, tube feeding or the threat of it, isolation, hospitalization with strict nursing care, massage, electric stimulation, and hydrotherapy. Attempts to treat the emotional aspect have included simple suggestion, discussion, psychotherapy, psychoanalysis, hypnosis, insulin shock, and frontal lobotomy. At one time, each of the following has been in vogue: pituitary extract, implanted calves’ pituitary, adrenocorticotropic hormone, corticosteroids, thyroid extract, estrogen, and insulin. Most of the patients in the present series were evaluated and managed by the same physician on an outpatient basis.ll The program of treatment was basically the same
for all patients: unhurried supportive psychotherapy for from 4 to 6 weeks, during which time a high-protein, high-vitamin diet progressed from about 1,400 calories per day to about 3,600 calories per day. A few patients required hospitalization because of extreme emaciation, and their initial treatment included tube feeding and intravenously administered fluids. Cyclic estrogen therapy was given to some patients who were seen after many months of amenorrhea, in an effort to prime the uterus for the return of menstruation. We believe that there are two factors of prognostic significance for recovery from anorexia nervosa and hence for return of normal menstruation and fertility. These factors are age at onset of anorexia nervosa and percentage of weight lost. It is evident from Fig. 1 that the onset of anorexia nervosa prior to 23 years of age is associated with a good outlook for recovery, but when the illness begins at age 23 years or after, the outlook is only fair. Similarly, a weight loss of as much as 30 per cent of the original weight is associated with an excellent outlook for recovery; whereas a weight loss of more than 30 per cent is associated with only a fair prognosis (Fig. 2) . Menstrual function in anorexia nervosa is not wholly dependent on loss or gain of weight. This is indicated in our study by several patients who became amenorrheic prior to the onset of weight loss and several who remained amenorrheic for some months to years after apparent recovery. Russel and co-workerslGj I7 in England have recently studied estrogen and gonadotropin excretion during refeeding in patients with anorexia nervosa. They observed a persisting absence of cyclic activity, which they believed was a hypothalamic effect and concluded that malnutrition in anorexia nervosa was only partly responsible for menstrual abnormalities. Ccrtain of the clinical characteristics that occur in patients with anorexia nervosa-their refusal of food, weight loss, amenorrhea, and disturbances in water regulation-may be reproduced in the experimental model. Rus-
Menstruation
sell6 postulates “. . . that the anorexia induced by the hypothalamic disturbance engenders the abnormal thinking that commonly occurs--the revulsion for fattening foods and the preoccupation with body weight and body image. In addition, failure of the gonads
and fertility
in anorexia
nervosa
379
would be held responsible for these patients failing to reach full psychosexual maturity.” Thus the hypothalamic disturbance he is postulating must allow for a disorder that may fluctuate over long periods, but from which complete recovery is possible.
REFERENCES
1. Allbutt,
2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
C.: Neuroses of the Stomach and of Other Parts of the Abdomen, in Allbutt, C., and Rolleston, H. D.: System of Medicine, London, 1908, The Macmillan Company, Ltd., vol. III, p. 398. Berkman, J. M.: Am. J. M. SC. 180: 411, 1930. Berkman, J. M.: M. Clin. North America 23: 9OL, 1939. Berkman, J. M.: Ann. Int. Med. 22: 679, 1945. Be:rkman, J. M.: Postgrad. Med. 3: 237, 1948. Bernstein, I. C.: Am. J. Psychiat. 120: 1023, 1964. Dally, P., and Sargant, W.: Brit. M. J. 2: 793, 1966. DeCarle, D. W.: S. Clin. North America 42: 92L, 1962. Escamilla, R. F.: J. Nerv. & Ment. Dis. 99: 583, 1944. Farquharson, R. F., and Hyland, H. H.: Canad. M. A. J. 94: 411, 1966. Gi6in, Mary E., Frazier, S. H., Robinson, D.
12. 13. 14. 15. 16. 17.
18. 19. 20. 21. 22.
B., and Johnson, Adelaide M.: Proc. Staff Meet., Mayo Clin. 32: 171, 1957. Gull, W. W.: Brit. M. J. 2: 527, 1873. Kay, D. W. K.: Proc. Roy. Sot. Med. 46: 669, 1953. Laseque, Cl.: Arch. Gen. Med. 131: 385, 1873. Richardson, H. B.: Arch. Int. Med. (Chicago) 63: 1, 1939. Russel, G. F. M.: Proc. Roy. Sot. Med. 58: 811, 1965. Russel, G. F. M., Loraine, J. A., Bell, E. T., and Harkness, R. A.: J. Psychosom. Res. 9: 79, 1965. Sheehan, H. L.: J. Path. & Bact. 45: 189, 1937. Sheehan, H. L., and Murdoch, R.: J. Obst. Sr Gynaec. Brit. Comm. 45: 456, 1938. Simmonds, M.: Deutsch. Med. Wchnschr. 40: 322, 1914. Simmonds, M.: Deutsch. Med. Wchnschr. 42: 190, 1916. Simmonds, M.: Deutsch. Med. Wchnschr. 44: 852, 1918.