477
THE LANCET
Have I
Stopped Ovulating Yet?
question-asked by many perimenopausal a straightforward (and correct) answer. Unfortunately our present state of ignorance is such that only a guarded reply can be given. THIs
women-deserves
There is even some doubt as to whether the question is the right one. Does she really mean, "Am I still capable of becoming pregnant?" The two questions will not necessarily receive the same answer. Ovulation is generally believed to become less frequent in perimenopausal women.! However, menstrual patterns may vary considerably in women approaching the menopause.2 A study of 139 New Zealand women aged 40-55 years now suggests that the incidence of ovulation is related more closely to the regularity of menstruation than to the age of the patient. Of those women who reported no change in menstrual frequency, 95% ovulated in every cycle, whereas of those with a recent history of oligomenorrhoea only 34% ovulated consistently. Increasing cycle length was associated with diminishing incidence of ovulation. Nevertheless, laparoscopic evidence of ovulation is seen not uncommonly in women over the age of 504 and primordial follicles with apparently normal oocytes have been observed in the ovaries of old women.’ Pregnancy, on the other hand, is rare.6 In the U.S.A., 1 in 24 000 births is from a mother more than 50 years old. In the United Kingdom, 1 Sharman, A The Ovary, vol. I (edited by H Zuckerman); p. 645. New York, 1962 2 ireloar,A. E., Boynton, R. D., Benn, B. G., Brown, B. W. Int. J. Fertil.
1967, 12, 77. Sci. 1979, 11, 39. 3 Metcalf, M. G. biosoc. J 4 Novak, E. R Obstet. Gynec. 1970, 36, 903. 5 Costof, A., Mahesh, V. B. J. Am. Geriat. Soc. 1975, 23, 193. 6 W harton, L. R. Am. J. Obstet Gynec. 1964, 90, 672.
successful pregnancies after the age of 52 are extremely rare.7 Factors other than ovulation probably affect the ability to conceive in perimenopausal women.It has been suggested that the reduced fertility of older women is due to an increased incidence of short or inadequate luteal phases.9 However, no decrease in the size of the pregnanediol peak was observed in older women with regular 21-35 day cycles.3 Disordered ovum transport and delayed implantation are other possible explanations for the impaired fertility of older women.7 One of the difficulties inherent in such studies is the fact that the evidence of ovulation is generally circumstantial. Basal-body-temperature charts may be difficult to interpret. 10 Vaginal-mucus characteristics are useful in many women who are properly trained." The pregnanediol content of a random sample of urine (corrected for creatinine) provides a rapid, convenient, and reliable estimate of luteal function,12 but luteinisation may possibly occur without release of the ovum. Direct inspection of the corpus luteum at laparoscopy, or pregnancy, provides firmer but less convenient evidence. Plasma-gonadotrophin levels rise as ovarian function diminishes, and the plasma follicle-stimulating-hormone (F.S.H.) concentration has been reported to give a good indication of menopausal status.13 However, SHERMAN et al.14 have shown that ovulation may occur in perimenopausal women despite raised plasma-gonadotrophin concentrations. This difficulty is illustrated by an assessment of ovarian function in perimenopausal women who had stopped oral contraceptives. 15 Pituitary/ovarian function showed evidence of recovery from suppression in 80% of patients within one week of stopping the pill, and those who were capable of ovulating could be readily identified. However, 1 patient with a "postmenopausal" hormonal profile later showed evidence of ovulation. BROWN 16 has made detailed analyses of hormonal profiles in 85 climacteric women, and two of these subjects, studied by weekly urine collections for 6-7 years, showed practically every pattern of normal and abnormal ovarian activity yet documented. METCALF and DONALD 17 lately described how ovarian function fluctuated in a perimenopausal’woman during 2 years of observation. "Postmenopausal" 7 Francis, W. J. A. J. Reprod. Fertil. 1970, suppl. 12, p. 89. 8. Talbert, G. B. Am. J. Obstet. Gynec. 1968, 102, 451 9 Doring, G. K. J Reprod. Fertil. 1969, suppl. 6, p. 77. 10 Lenton, E. A., Weston, G. A., Cooke, I. D. Br. med. J. 1977, i, 803. 11 Billings, E. L., Billings, J. J., Brown, J. B., Burger, H. G Lancet, 1972, i, 282. 12. Metcalf, M. G. N.Z. med. J. 1976, 84, 150. 13. Chakravarti, S., Collins, W. P., Forecast, J. D., Newton, J R , Oram, D. H., Studd, J. W. W. Br. med. J 1976, ii, 784. 14. Sherman, B. M., West, J. H., Korenman, S. G. J. clin Endocr. Metab. 1976, 15.
42, 629. Donald, R. A., Baker, D. A., Metcalf, M. G., Turner, E. D. Br. J. Obstet.
Gynœc. 1978, 85, 70. Organon Lecture, Endocrine Society of Australia, Meeting, Sydney, August, 1978 Metcalf, M. G., Donald, R. A. N.Z. med. J. 1979, 89, 45
16. Brown, J. B. 17.
21st Annual
478
episodes with amenorrhoea, hot flushes, high F.S.H. levels, and low urinary oestrogens were followed by menstrual cycles in which the F.s.H. levels were low and there was an ovulatory pattern of oestrogen excretion. On several occasions they observed an unusual association of high urinary oestrogens with high gonadotrophin levels. Clearly pituitary and ovarian function can vary considerably (and not always in phase) in a woman approaching the menopause. and
failed to provide her with a yes/no answer. Perhaps her disappointment will encourage further studies of ovarian function in perimenopausal women.
pregnanediol
important that the patient is given the coradvice. On the one hand, if her fertility is underestimated, she may have to cope with an unexpected addition to her family, at an age when the risks associated with pregnancy are increased. Ori the other hand, the risks of oral contraception also increase with age,18 and other contraceptive methods are not without their complications. 19 Admittedly, for the increasing number of couples who have undergone vasectomy or tubal ligation, the question is of minor importance. A further consideration for the doctor is whether the patient’s secondary amenorrhoea is due to the menopause or there is some other explanation such as pregnancy, It is
rect
post-pill amenorrhoea, 20 or hyperprolactinæmia21 or other endocrine disorders. The knowledge that the average age of the menopause in most European communities is about 5 07,22 and that persistent anovulation is uncommon under the age of 453 assists in selection of patients for further investigation. The following guidelines are suggested. Regular menstruation implies regular ovulation irrespective of the patient’s age. However, conception is rare after the age of 50 and extremely rare after the age of 52. Women under the age of 50 who have amenorrhoea of more than a year’s duration (some would say 2 years) are very unlikely to ovulate subsequently. If hormonal evidence of ovulation is required, a pregnanediol estimation on a random sample of urine on day 21 of the cycle provides useful confirmation. Alternative diagnoses should be considered in women under the age of 45 presenting with secondary amenorrhoea. Persistently raised plasma-F.s.H. values suggest primary ovarian failure (at least at the time of sampling) and indicate that other investigations are likely to be unproductive. If the plasma-F.s.H. is not raised, then other explanations should be sought and measurement of plasma-prolactin should be considered. Our
patient
is
disappointed because
we
have
among Medical Patients
Psychiatric Illness
LiPOWSKi’ estimated that 30-60% of medical inpatients and 50-80% of medical outpatients have psychiatric illness severe enough to demand special attention. Until lately investigators have used widely differing criteria for what constitutes a psychiatric case, but with the arrival of psychiatric screening tests and standardised diagnostic research interviews comparisons become possible. GLASSand his colleagues2 applied the Hopkins Symptom Checklist and a psychiatric research interview to 82 medical outpatients attending the University of Chicago Hospitals, and used the FEIGHNER criteria3to diagnose psychiatric illness. The symptom checklist was not very helpful in separating psychiatrically ill from well patients, but the investigators made psychiatric diagnoses in no fewer than 83% of the patients. These workers
that the mean checklist scores were similar to those found by GOLDBERG 4,1 for patients attending general practitioners in Philadelphia, yet in that survey the prevalence of psychiatric illness was only 25%. In Philadelphia the illnesses were diagnosed with the Clinical Interview Schedule6 designed at the Institute of Psychiatry, London. Since in both surveys most of the diagnoses were of minor affective disorder, the British criteria are presumably narrower that those of FEIGHNER. The rather lower prevalence figures found by British investigators among medical outpatients would be consistent with this: CULPAN and DAVIES7 detected psychiatric illness in 31% of newly referred patients to Dulwich Hospital, and GOLDBERG8 in 34% of patients with diseases of the small intestine attending a follow-up clinic at St. Thomas’. These rates are close to those in patients attending a general practitioner5,9 and are substantially higher than those in note
the community at large.
10,11 investigators have used standardised case-finding techniques on medical inpatients, Several
Lipowski, Z. J. Psychosom. Med. 1967, 29, 201. Glass, R., Allan, A., Uhlenhuth, E., Kimball, C., Borinstein, D. Archs gen. Psychiat. 1978, 35, 1189. 3. Feighner, J. P., Robins, E., Guze, S. B. ibid. 1972, 26, 57. 4. Goldberg, D. Detection of Psychiatric Illness by Questionnaire. London. 1. 2.
1974. 5.
of General Practitioners Oral Contraception Study. Lancet, 1977, ii, 727. 19. Vessey, M., Doll, R., Peto, R., Johnson, B., Wiggins, P. J biosoc. Sci. 1976, 8, 373. 20. Shearman, R. Lancet, 1971, ii, 64. 21. Thorner, M. O., McNeilly, A. S., Hagan, C., Besser, G. M. Br. med. J. 1974, ii, 419. 22. Burch, P. R. J., Gunz, F W. N.Z. med J. 1967, 66, 6 18.
Royal College
Goldberg, D., Rickels, K., Downing, R., Hesbacher, P. Br J. Psychiat. 1976, 129, 61. 6. Goldberg, D., Cooper, B., Eastwood, M. R., Kedward, H. B., Shepherd, M Brit. J. prev. soc. Med. 1970, 24, 18.
Culpan, R , Davies, B Comprehens. Psychiat 1960, 1, 228. Goldberg, D. Gut, 1970, 11, 459. Goldberg, D., Blackwell, B. Br. med J. 1970, ii, 439. 10. Goldberg, D., Kay, C., Thompson, L Psychol Med 1976, 6, 565. 11. Culpan, R., Davies, B. M., Oppenheim, A. N. Br med. J. 1960, i, 855. 7. 8 9.
THE LANCET
Have I
Stopped Ovulating Yet?
question-asked by many perimenopausal a straightforward (and correct) answer. Unfortunately our present state of ignorance is such that only a guarded reply can be given. THIs
women-deserves
There is even some doubt as to whether the question is the right one. Does she really mean, "Am I still capable of becoming pregnant?" The two questions will not necessarily receive the same answer. Ovulation is generally believed to become less frequent in perimenopausal women.! However, menstrual patterns may vary considerably in women approaching the menopause.2 A study of 139 New Zealand women aged 40-55 years now suggests that the incidence of ovulation is related more closely to the regularity of menstruation than to the age of the patient. Of those women who reported no change in menstrual frequency, 95% ovulated in every cycle, whereas of those with a recent history of oligomenorrhoea only 34% ovulated consistently. Increasing cycle length was associated with diminishing incidence of ovulation. Nevertheless, laparoscopic evidence of ovulation is seen not uncommonly in women over the age of 504 and primordial follicles with apparently normal oocytes have been observed in the ovaries of old women.’ Pregnancy, on the other hand, is rare.6 In the U.S.A., 1 in 24 000 births is from a mother more than 50 years old. In the United Kingdom, 1 Sharman, A The Ovary, vol. I (edited by H Zuckerman); p. 645. New York, 1962 2 ireloar,A. E., Boynton, R. D., Benn, B. G., Brown, B. W. Int. J. Fertil.
1967, 12, 77. Sci. 1979, 11, 39. 3 Metcalf, M. G. biosoc. J 4 Novak, E. R Obstet. Gynec. 1970, 36, 903. 5 Costof, A., Mahesh, V. B. J. Am. Geriat. Soc. 1975, 23, 193. 6 W harton, L. R. Am. J. Obstet Gynec. 1964, 90, 672.
successful pregnancies after the age of 52 are extremely rare.7 Factors other than ovulation probably affect the ability to conceive in perimenopausal women.It has been suggested that the reduced fertility of older women is due to an increased incidence of short or inadequate luteal phases.9 However, no decrease in the size of the pregnanediol peak was observed in older women with regular 21-35 day cycles.3 Disordered ovum transport and delayed implantation are other possible explanations for the impaired fertility of older women.7 One of the difficulties inherent in such studies is the fact that the evidence of ovulation is generally circumstantial. Basal-body-temperature charts may be difficult to interpret. 10 Vaginal-mucus characteristics are useful in many women who are properly trained." The pregnanediol content of a random sample of urine (corrected for creatinine) provides a rapid, convenient, and reliable estimate of luteal function,12 but luteinisation may possibly occur without release of the ovum. Direct inspection of the corpus luteum at laparoscopy, or pregnancy, provides firmer but less convenient evidence. Plasma-gonadotrophin levels rise as ovarian function diminishes, and the plasma follicle-stimulating-hormone (F.S.H.) concentration has been reported to give a good indication of menopausal status.13 However, SHERMAN et al.14 have shown that ovulation may occur in perimenopausal women despite raised plasma-gonadotrophin concentrations. This difficulty is illustrated by an assessment of ovarian function in perimenopausal women who had stopped oral contraceptives. 15 Pituitary/ovarian function showed evidence of recovery from suppression in 80% of patients within one week of stopping the pill, and those who were capable of ovulating could be readily identified. However, 1 patient with a "postmenopausal" hormonal profile later showed evidence of ovulation. BROWN 16 has made detailed analyses of hormonal profiles in 85 climacteric women, and two of these subjects, studied by weekly urine collections for 6-7 years, showed practically every pattern of normal and abnormal ovarian activity yet documented. METCALF and DONALD 17 lately described how ovarian function fluctuated in a perimenopausal’woman during 2 years of observation. "Postmenopausal" 7 Francis, W. J. A. J. Reprod. Fertil. 1970, suppl. 12, p. 89. 8. Talbert, G. B. Am. J. Obstet. Gynec. 1968, 102, 451 9 Doring, G. K. J Reprod. Fertil. 1969, suppl. 6, p. 77. 10 Lenton, E. A., Weston, G. A., Cooke, I. D. Br. med. J. 1977, i, 803. 11 Billings, E. L., Billings, J. J., Brown, J. B., Burger, H. G Lancet, 1972, i, 282. 12. Metcalf, M. G. N.Z. med. J. 1976, 84, 150. 13. Chakravarti, S., Collins, W. P., Forecast, J. D., Newton, J R , Oram, D. H., Studd, J. W. W. Br. med. J 1976, ii, 784. 14. Sherman, B. M., West, J. H., Korenman, S. G. J. clin Endocr. Metab. 1976, 15.
42, 629. Donald, R. A., Baker, D. A., Metcalf, M. G., Turner, E. D. Br. J. Obstet.
Gynœc. 1978, 85, 70. Organon Lecture, Endocrine Society of Australia, Meeting, Sydney, August, 1978 Metcalf, M. G., Donald, R. A. N.Z. med. J. 1979, 89, 45
16. Brown, J. B. 17.
21st Annual
478
episodes with amenorrhoea, hot flushes, high F.S.H. levels, and low urinary oestrogens were followed by menstrual cycles in which the F.s.H. levels were low and there was an ovulatory pattern of oestrogen excretion. On several occasions they observed an unusual association of high urinary oestrogens with high gonadotrophin levels. Clearly pituitary and ovarian function can vary considerably (and not always in phase) in a woman approaching the menopause. and
failed to provide her with a yes/no answer. Perhaps her disappointment will encourage further studies of ovarian function in perimenopausal women.
pregnanediol
important that the patient is given the coradvice. On the one hand, if her fertility is underestimated, she may have to cope with an unexpected addition to her family, at an age when the risks associated with pregnancy are increased. Ori the other hand, the risks of oral contraception also increase with age,18 and other contraceptive methods are not without their complications. 19 Admittedly, for the increasing number of couples who have undergone vasectomy or tubal ligation, the question is of minor importance. A further consideration for the doctor is whether the patient’s secondary amenorrhoea is due to the menopause or there is some other explanation such as pregnancy, It is
rect
post-pill amenorrhoea, 20 or hyperprolactinæmia21 or other endocrine disorders. The knowledge that the average age of the menopause in most European communities is about 5 07,22 and that persistent anovulation is uncommon under the age of 453 assists in selection of patients for further investigation. The following guidelines are suggested. Regular menstruation implies regular ovulation irrespective of the patient’s age. However, conception is rare after the age of 50 and extremely rare after the age of 52. Women under the age of 50 who have amenorrhoea of more than a year’s duration (some would say 2 years) are very unlikely to ovulate subsequently. If hormonal evidence of ovulation is required, a pregnanediol estimation on a random sample of urine on day 21 of the cycle provides useful confirmation. Alternative diagnoses should be considered in women under the age of 45 presenting with secondary amenorrhoea. Persistently raised plasma-F.s.H. values suggest primary ovarian failure (at least at the time of sampling) and indicate that other investigations are likely to be unproductive. If the plasma-F.s.H. is not raised, then other explanations should be sought and measurement of plasma-prolactin should be considered. Our
patient
is
disappointed because
we
have
among Medical Patients
Psychiatric Illness
LiPOWSKi’ estimated that 30-60% of medical inpatients and 50-80% of medical outpatients have psychiatric illness severe enough to demand special attention. Until lately investigators have used widely differing criteria for what constitutes a psychiatric case, but with the arrival of psychiatric screening tests and standardised diagnostic research interviews comparisons become possible. GLASSand his colleagues2 applied the Hopkins Symptom Checklist and a psychiatric research interview to 82 medical outpatients attending the University of Chicago Hospitals, and used the FEIGHNER criteria3to diagnose psychiatric illness. The symptom checklist was not very helpful in separating psychiatrically ill from well patients, but the investigators made psychiatric diagnoses in no fewer than 83% of the patients. These workers
that the mean checklist scores were similar to those found by GOLDBERG 4,1 for patients attending general practitioners in Philadelphia, yet in that survey the prevalence of psychiatric illness was only 25%. In Philadelphia the illnesses were diagnosed with the Clinical Interview Schedule6 designed at the Institute of Psychiatry, London. Since in both surveys most of the diagnoses were of minor affective disorder, the British criteria are presumably narrower that those of FEIGHNER. The rather lower prevalence figures found by British investigators among medical outpatients would be consistent with this: CULPAN and DAVIES7 detected psychiatric illness in 31% of newly referred patients to Dulwich Hospital, and GOLDBERG8 in 34% of patients with diseases of the small intestine attending a follow-up clinic at St. Thomas’. These rates are close to those in patients attending a general practitioner5,9 and are substantially higher than those in note
the community at large.
10,11 investigators have used standardised case-finding techniques on medical inpatients, Several
Lipowski, Z. J. Psychosom. Med. 1967, 29, 201. Glass, R., Allan, A., Uhlenhuth, E., Kimball, C., Borinstein, D. Archs gen. Psychiat. 1978, 35, 1189. 3. Feighner, J. P., Robins, E., Guze, S. B. ibid. 1972, 26, 57. 4. Goldberg, D. Detection of Psychiatric Illness by Questionnaire. London. 1. 2.
1974. 5.
of General Practitioners Oral Contraception Study. Lancet, 1977, ii, 727. 19. Vessey, M., Doll, R., Peto, R., Johnson, B., Wiggins, P. J biosoc. Sci. 1976, 8, 373. 20. Shearman, R. Lancet, 1971, ii, 64. 21. Thorner, M. O., McNeilly, A. S., Hagan, C., Besser, G. M. Br. med. J. 1974, ii, 419. 22. Burch, P. R. J., Gunz, F W. N.Z. med J. 1967, 66, 6 18.
Royal College
Goldberg, D., Rickels, K., Downing, R., Hesbacher, P. Br J. Psychiat. 1976, 129, 61. 6. Goldberg, D., Cooper, B., Eastwood, M. R., Kedward, H. B., Shepherd, M Brit. J. prev. soc. Med. 1970, 24, 18.
Culpan, R , Davies, B Comprehens. Psychiat 1960, 1, 228. Goldberg, D. Gut, 1970, 11, 459. Goldberg, D., Blackwell, B. Br. med J. 1970, ii, 439. 10. Goldberg, D., Kay, C., Thompson, L Psychol Med 1976, 6, 565. 11. Culpan, R., Davies, B. M., Oppenheim, A. N. Br med. J. 1960, i, 855. 7. 8 9.
