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Long-term dangers of hormonal treatment
Turner’s patients have a small marker derived from the Y chromosome that is not detected by routine cytogenetic analysis when only present in a small fraction of the cells. The finding of Y-derived sequences in cytogenetically 45,X Turner’s patients is the first evidence that Turner’s syndrome and mixed gonadal dysgenesis present a phenotypic and biological continuum rather than different entities, especially since the rate of mosaicism may be higher in gonadal tissue. The clinical importance of a low number of Y-positive cells in 45,X patients in terms of an increased risk for gonadal neoplasms and/or virilisation remains to be investigated.
Mirjana Kocova, Massimio Trucco Division of Immunogenetics, Department of Pediatrics, Children’s Hospital of Pittsburgh, PA 15213, USA
1
2
discontinuing hormones within 12 months were not followed up. The 1963-84 death rate (124) was compared favourably with a national rate of 212per 100 000 women-an apparent reduction to 058. Three years later breast cancer deaths had doubled from 0-55 to 1,00.4 McPhersonshas predicted that early-stage longer-term pill takers may have a one-in-four risk of developing breast cancer. Have politics and therapeutic dogmas controlled women’s health for too long? Ellen C G Grant 20 Coombe
1
Grady D, Rubin SM, Pettiti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med
2 3
Grant ECG. Sexual chemistry. London: Cedar, Reed Books, 1994. Vessey MP, McPherson K, Yeates D. Mortality in oral contraceptive users. Lancet 1981; i: 549-50. Hunt K, Vessey M, McPherson K. Mortality in a cohort of long-term users of hormone replacement therapy: an updated analysis. Br J Obstet Gynaecol 1990; 97: 1080-86. McPherson K. Latent effects in the interpretation of any association between oral contraceptives and breast cancer. In: Mansel RE, ed. Recent developments in the study of benign breast disease. Carnforth, Lancashire: Parthenon, 1991: 165-75.
Rangos Research Center,
Kocova M, Siegel SF, Wenger SL, Lee PA, Trucco M. Detection of Y chromosome sequences in Turner’s syndrome by Southern blot analysis of amplified DNA. Lancet 1993; 342: 140-43. Held KR. Turner’s syndrome and chromosome Y. Lancet 1993; 342: 128-29.
Vollrath D, Foote S, Hilton A, et al. The human Y chromosome: a 43-interval map based on naturally occurring deletions. Science 1992; 258: 52-59. 4 Warburton PE, Greig GM, Haaf T, Willard HF. PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis. Genomics 1991; 11: 325-33. 3
Ridings, Kingston-upon-Thames KT2 7JU, UK
1992; 117: 12:1016-37.
4
5
Hysteria or pulled elbow? Long-term dangers of hormonal treatment SIR-te Velde (Mar 12, p 654) asks for large-scale randomised trials of long-term hormone treatment because there are no unbiased epidemiological data. Do exogenous hormones prevent disease? In Grady and colleagues’ meta-analysis of 39 studies1 the risks of breast cancer with oestrogen-only hormone therapy ranged from 0-2 to 3(and with added progestagens from 0-2 to 4-4), endometrial cancer risks were 0-4-20; coronary artery disease risk with oestrogens was 0-3-4-2, and cerebrovascular disease risk was 02-23. Oestrogen use equivalent to 0 625 mg of conjugated oestrogen daily reduced the risk of hip fracture by 0-25 but reached unity six or more years after therapy. Grady et al concluded that for most women "the best course of action is unclear". I have detailed2 the importance of investigating exogenous steroid hormone induced alterations to minerals, vitamins, and essential fatty acids. For example, women taking hormones tend to have lower serum concentrations of zinc, magnesium, manganese, and bone alkaline phosphatase, and higher copper concentrations than other postmenopausal women with
osteoporosis. Long-term data are scarce because of very poor compliance, with few older women taking hormones for more than five years because of side-effects. Meanwhile the effects of short hormone exposure can be seen as nationwide increases in hormone-dependent cancers. Office of Population Censuses and Surveys breast cancer registrations for England and Wales increased by 50-7% between 1962 and 1987, and deaths to 1990 rose by 31% (389-510 per million women). The claims that hormone therapy prevents death and vascular disease may be spurious for the reasons given by te Velde. It is noteworthy that when the Oxford Family Planning Association oral contraceptive study (1968-79) reported lower death rates for pill takers than for all women in England and Wales (52 -9 vs 108per 100 000 women) it was not generally claimed that oral contraceptives reduced deaths by half. The control groups also had low death rates, and potential causes of death, such as invasive cervical cancer, suicide attempts, and vascular illnesses, were increased among pill takers. By contrast, the British Hormone Replacement Therapy cohort had no comparable control group and women 926
SiR-Most research agrees that hysterical loss of function is rare below the age of 5 years. Such observations are usually qualified by reference to this boy described by Anna Freud in 1923.1 After he saw a bucket crash into a well and "After his mother and he had gone back into the house, while she was beginning to take off his little coat, he suddenly began to scream and cry, calling out that his arm hurt him, that they must not touch it". She "became frightened at the look of his arm, which he kept rigidly bent" and "while the arm was being examined the child screamed as if in torments". He "played, without ever moving his arm; when anyone tried to touch it he screamed. When he was asleep ... his mother tried to touch the arm, and she sat down by his bed with a immediately he woke up friend and played with him ... in such a diverting way that he gradually became more lively and forgot everything, and finally stretched, lifted, turned, and dropped both arms, while playing at being a bird and flying... nothing more was heard of his arm hurting him". Anna Freud explained the rigid posture of his arm as self punishment for masturbation and the way in which he held it tightly pressed against his body as a precautionary measure against castration. It seems more probable that this boy had a pulled elbow,2 which reduced spontaneously during arm flapping, and that he was not hysterical at all. ...
Michael Prendergast The Children’s
1 2
Hospital, Ladywood Middleway, Birmingham B16 8ET,
UK
Freud A. Introduction to psychoanalysis. London: Hogarth Press (Institute of Psychoanalysis), 1974. Illingworth CM. Pulled elbow: a study of 100 patients. BMJ 1975; ii: 672-74.
CORRECTIONS Randomising means, not aims in clinical trials-In this letter by Widder (Feb 5, p 359) the second sentence in the second paragraph should have read "Before even considering a study the patients must be asked and helped...". syndromes-In this grand round by Dr Charis Eng and colleagues (Mar 19, p 709), the data given for van Hippel Lindau in table I Familial cancer should
read
chromosome
haemangioblastomas.
3
and
renal
cell
carcinomas
and
Mirjana Kocova, Massimio Trucco Division of Immunogenetics, Department of Pediatrics, Children’s Hospital of Pittsburgh, PA 15213, USA
1
2
discontinuing hormones within 12 months were not followed up. The 1963-84 death rate (124) was compared favourably with a national rate of 212per 100 000 women-an apparent reduction to 058. Three years later breast cancer deaths had doubled from 0-55 to 1,00.4 McPhersonshas predicted that early-stage longer-term pill takers may have a one-in-four risk of developing breast cancer. Have politics and therapeutic dogmas controlled women’s health for too long? Ellen C G Grant 20 Coombe
1
Grady D, Rubin SM, Pettiti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med
2 3
Grant ECG. Sexual chemistry. London: Cedar, Reed Books, 1994. Vessey MP, McPherson K, Yeates D. Mortality in oral contraceptive users. Lancet 1981; i: 549-50. Hunt K, Vessey M, McPherson K. Mortality in a cohort of long-term users of hormone replacement therapy: an updated analysis. Br J Obstet Gynaecol 1990; 97: 1080-86. McPherson K. Latent effects in the interpretation of any association between oral contraceptives and breast cancer. In: Mansel RE, ed. Recent developments in the study of benign breast disease. Carnforth, Lancashire: Parthenon, 1991: 165-75.
Rangos Research Center,
Kocova M, Siegel SF, Wenger SL, Lee PA, Trucco M. Detection of Y chromosome sequences in Turner’s syndrome by Southern blot analysis of amplified DNA. Lancet 1993; 342: 140-43. Held KR. Turner’s syndrome and chromosome Y. Lancet 1993; 342: 128-29.
Vollrath D, Foote S, Hilton A, et al. The human Y chromosome: a 43-interval map based on naturally occurring deletions. Science 1992; 258: 52-59. 4 Warburton PE, Greig GM, Haaf T, Willard HF. PCR amplification of chromosome-specific alpha satellite DNA: definition of centromeric STS markers and polymorphic analysis. Genomics 1991; 11: 325-33. 3
Ridings, Kingston-upon-Thames KT2 7JU, UK
1992; 117: 12:1016-37.
4
5
Hysteria or pulled elbow? Long-term dangers of hormonal treatment SIR-te Velde (Mar 12, p 654) asks for large-scale randomised trials of long-term hormone treatment because there are no unbiased epidemiological data. Do exogenous hormones prevent disease? In Grady and colleagues’ meta-analysis of 39 studies1 the risks of breast cancer with oestrogen-only hormone therapy ranged from 0-2 to 3(and with added progestagens from 0-2 to 4-4), endometrial cancer risks were 0-4-20; coronary artery disease risk with oestrogens was 0-3-4-2, and cerebrovascular disease risk was 02-23. Oestrogen use equivalent to 0 625 mg of conjugated oestrogen daily reduced the risk of hip fracture by 0-25 but reached unity six or more years after therapy. Grady et al concluded that for most women "the best course of action is unclear". I have detailed2 the importance of investigating exogenous steroid hormone induced alterations to minerals, vitamins, and essential fatty acids. For example, women taking hormones tend to have lower serum concentrations of zinc, magnesium, manganese, and bone alkaline phosphatase, and higher copper concentrations than other postmenopausal women with
osteoporosis. Long-term data are scarce because of very poor compliance, with few older women taking hormones for more than five years because of side-effects. Meanwhile the effects of short hormone exposure can be seen as nationwide increases in hormone-dependent cancers. Office of Population Censuses and Surveys breast cancer registrations for England and Wales increased by 50-7% between 1962 and 1987, and deaths to 1990 rose by 31% (389-510 per million women). The claims that hormone therapy prevents death and vascular disease may be spurious for the reasons given by te Velde. It is noteworthy that when the Oxford Family Planning Association oral contraceptive study (1968-79) reported lower death rates for pill takers than for all women in England and Wales (52 -9 vs 108per 100 000 women) it was not generally claimed that oral contraceptives reduced deaths by half. The control groups also had low death rates, and potential causes of death, such as invasive cervical cancer, suicide attempts, and vascular illnesses, were increased among pill takers. By contrast, the British Hormone Replacement Therapy cohort had no comparable control group and women 926
SiR-Most research agrees that hysterical loss of function is rare below the age of 5 years. Such observations are usually qualified by reference to this boy described by Anna Freud in 1923.1 After he saw a bucket crash into a well and "After his mother and he had gone back into the house, while she was beginning to take off his little coat, he suddenly began to scream and cry, calling out that his arm hurt him, that they must not touch it". She "became frightened at the look of his arm, which he kept rigidly bent" and "while the arm was being examined the child screamed as if in torments". He "played, without ever moving his arm; when anyone tried to touch it he screamed. When he was asleep ... his mother tried to touch the arm, and she sat down by his bed with a immediately he woke up friend and played with him ... in such a diverting way that he gradually became more lively and forgot everything, and finally stretched, lifted, turned, and dropped both arms, while playing at being a bird and flying... nothing more was heard of his arm hurting him". Anna Freud explained the rigid posture of his arm as self punishment for masturbation and the way in which he held it tightly pressed against his body as a precautionary measure against castration. It seems more probable that this boy had a pulled elbow,2 which reduced spontaneously during arm flapping, and that he was not hysterical at all. ...
Michael Prendergast The Children’s
1 2
Hospital, Ladywood Middleway, Birmingham B16 8ET,
UK
Freud A. Introduction to psychoanalysis. London: Hogarth Press (Institute of Psychoanalysis), 1974. Illingworth CM. Pulled elbow: a study of 100 patients. BMJ 1975; ii: 672-74.
CORRECTIONS Randomising means, not aims in clinical trials-In this letter by Widder (Feb 5, p 359) the second sentence in the second paragraph should have read "Before even considering a study the patients must be asked and helped...". syndromes-In this grand round by Dr Charis Eng and colleagues (Mar 19, p 709), the data given for van Hippel Lindau in table I Familial cancer should
read
chromosome
haemangioblastomas.
3
and
renal
cell
carcinomas
and