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On menstrual bleeding with hormone replacement therapy
exposed (or not) to selected literary works-though the impact on behaviour would doubtless have to be assessed by role play. John Bignall The Lancet, London, UK
1
2
Novack DH, Volk G, Droperman DA, Lipkin M. Medical interviewing and interpersonal skills teaching in US medical schools. JAMA 1993; 269: 2101-05. Anon. Climbing back up. BMJ 1993; 307: 742-43.
On menstrual
bleeding with replacement therapy
hormone
replacement therapy is increasingly used for the of menopausal complaints and for prevention longer term effects of hormone depletion. In women
Hormone
treatment
of with an intact uterus, the oestrogen component needs to be combined with a progestagen to avoid an increased risk of endometrial cancer. Cyclical addition of progestagen induces monthly menstrual bleeding; many women find this inconvenient (women will have experienced an average of 400 menstruations between the menarche and the menopause’) and some will stop taking the medication.2 To avoid bleeding and increase compliance continous combined oestrogen/progestagen regimens have been advocated.3 MacLennan et al4 lately reported a 12-month randomised trial of three progestagens acetate, (medroxyprogesterone levonorgestrel, norethisterone) given orally in continuous combination with conjugated equine oestrogens. The study subjects were 75 women who had previously received cyclical hormone replacement therapy. These researchers concluded that these continuous oestrogen and progestagen regimens are an appropriate option for postmenopausal women who wish to avoid withdrawal
Cyclic regimens inducing regular withdrawal bleeding are appropriate. Measurements of blood loss during withdrawal bleeding show that these episodes are similar to or lighter than premenopausal periods.’8 Such studies are essential since women are unreliable judges of their menstrual loss and the correlation between subjective and measured loss, at least in young women, is poor.’ Median blood loss averaged 20 mL after 3 months’ therapy with the three regimens examined.7,8 This loss compares well with that of the premenopausal population, in whom the more
median is 35 mL and the 90th centile is 80 mL.9 Moreover, when treatment was continued, median blood loss gradually diminished being 17 mL after 12 months. Some perimenopausal women, especially those with menorrhagia, prefer an amenorrhoeic regimen of hormone replacement therapy. Population studies have shown that the amount of blood loss in women around age 50 is larger than that of younger women.9 Amenorrhoea cannot reliably be achieved with oral progestagen in this group. Uterine delivery of the progestagen levonorgestrel by way of a contraceptive device results in amenorrhoea and is an effective treatment for menorrhagia. This device has been used in 18 perimenopausal women, who also received oral oestrogen. After 12 months’ treatment, 15 were amenorrhoeic and endometrial biopsy specimens showed no sign of proliferation. 10 Overall, the therapeutic options for the climacteric have increased during recent years: the short-term goal is to achieve an acceptable bleeding pattern and thereby enhance patient compliance.
Margaret Rees Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, UK
1
Rees MCP. Menstrual problems. In: McPherson A, ed. Women’s problems in general practice. 3rd ed. Oxford: Oxford University Press,
2
Coope J, Marsh J.
1993: 171-97.
bleeding. do continuous combined regimens prevent bleeding? Continuous progestagen stimulation keeps the endometrium atrophic, as has been shown for long-term use in women treated for a mean of 3’9 years, in whom the endometrium was examined both hysteroscopically and histologically.5 Bleeding during the first few months of therapy, in most cases light bleeding or spotting, is not unusual. The frequency of bleeding gradually decreases, and at 12 months most women are amenorrhoeic.6 The incidence of bleeding is lower the longer the woman has been postmenopausal. Irregular bleeding is more likely if in continuous combined are used regimens perimenopausal women, and therefore this form of treatment should be reserved for postmenopausal women who have experienced their last period at least 6 months previously. The same caveat applies to tibolone, a compound with combined oestrogenic, progestagenic, and androgenic actions; in this case 12 months’ amenorrhoea is recommended before starting treatment. What can be done to help perimenopausal women who have climacteric symptoms but are still menstruating? How
250
3
Can we improve compliance with long-term HRT? Maturitas 1992; 15: 151-58. Staland B. Continuous treatment with natural oestrogens and progestogens. A method to avoid endometrial stimulation. Maturitas
1981; 3: 14-151. MacLennan AH, MacLennan A, Wenzel S, Chambers HM, Eckert K. Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial. Med J Aust 1993;159: 10206. 5 Hawthorn RJS, Spowart K, Walsh D, McKay Hart D. The endometrial status of women on long term continuous combined hormone replacement therapy. Br J Obstet Gynaecol 1991; 98: 939-42. 6 Christiansen C, Riis BJ. Five years with continuous combined oestrogen/progestogen therapy: effects on calcium metabolism, lipoproteins, and bleeding pattern. Br J Obstet Gynaecol 1990; 97: 1087-92. 7 Rees MCP, Barlow DH. Quantitation of hormone replacement induced withdrawal bleeds. Br J Obstet Gynaecol 1991; 98: 106-07. 8 Sporrong T, Rybo G, Mattson LA, Vilbergson G, Crona N. An objective and subjective assessment of uterine blood loss in postmenopausal women on hormone replacement therapy. Br J Obstet Gynaecol 1992; 99: 399-401. 9 Hallberg L, Hogdahl AM, Nilsson I, Rybo G. Menstrual blood loss: a population study. Acta Obstet Gynecol Scand 1966; 45: 320-51. 10 Anderson K, Mattson LA, Rybo G, Stadberg E. Intrauterine release of levonorgestrel: a new way of adding progestogen in hormone replacement therapy. Obstet Gynecol 1992; 79: 963-67. 4
1
2
Novack DH, Volk G, Droperman DA, Lipkin M. Medical interviewing and interpersonal skills teaching in US medical schools. JAMA 1993; 269: 2101-05. Anon. Climbing back up. BMJ 1993; 307: 742-43.
On menstrual
bleeding with replacement therapy
hormone
replacement therapy is increasingly used for the of menopausal complaints and for prevention longer term effects of hormone depletion. In women
Hormone
treatment
of with an intact uterus, the oestrogen component needs to be combined with a progestagen to avoid an increased risk of endometrial cancer. Cyclical addition of progestagen induces monthly menstrual bleeding; many women find this inconvenient (women will have experienced an average of 400 menstruations between the menarche and the menopause’) and some will stop taking the medication.2 To avoid bleeding and increase compliance continous combined oestrogen/progestagen regimens have been advocated.3 MacLennan et al4 lately reported a 12-month randomised trial of three progestagens acetate, (medroxyprogesterone levonorgestrel, norethisterone) given orally in continuous combination with conjugated equine oestrogens. The study subjects were 75 women who had previously received cyclical hormone replacement therapy. These researchers concluded that these continuous oestrogen and progestagen regimens are an appropriate option for postmenopausal women who wish to avoid withdrawal
Cyclic regimens inducing regular withdrawal bleeding are appropriate. Measurements of blood loss during withdrawal bleeding show that these episodes are similar to or lighter than premenopausal periods.’8 Such studies are essential since women are unreliable judges of their menstrual loss and the correlation between subjective and measured loss, at least in young women, is poor.’ Median blood loss averaged 20 mL after 3 months’ therapy with the three regimens examined.7,8 This loss compares well with that of the premenopausal population, in whom the more
median is 35 mL and the 90th centile is 80 mL.9 Moreover, when treatment was continued, median blood loss gradually diminished being 17 mL after 12 months. Some perimenopausal women, especially those with menorrhagia, prefer an amenorrhoeic regimen of hormone replacement therapy. Population studies have shown that the amount of blood loss in women around age 50 is larger than that of younger women.9 Amenorrhoea cannot reliably be achieved with oral progestagen in this group. Uterine delivery of the progestagen levonorgestrel by way of a contraceptive device results in amenorrhoea and is an effective treatment for menorrhagia. This device has been used in 18 perimenopausal women, who also received oral oestrogen. After 12 months’ treatment, 15 were amenorrhoeic and endometrial biopsy specimens showed no sign of proliferation. 10 Overall, the therapeutic options for the climacteric have increased during recent years: the short-term goal is to achieve an acceptable bleeding pattern and thereby enhance patient compliance.
Margaret Rees Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, UK
1
Rees MCP. Menstrual problems. In: McPherson A, ed. Women’s problems in general practice. 3rd ed. Oxford: Oxford University Press,
2
Coope J, Marsh J.
1993: 171-97.
bleeding. do continuous combined regimens prevent bleeding? Continuous progestagen stimulation keeps the endometrium atrophic, as has been shown for long-term use in women treated for a mean of 3’9 years, in whom the endometrium was examined both hysteroscopically and histologically.5 Bleeding during the first few months of therapy, in most cases light bleeding or spotting, is not unusual. The frequency of bleeding gradually decreases, and at 12 months most women are amenorrhoeic.6 The incidence of bleeding is lower the longer the woman has been postmenopausal. Irregular bleeding is more likely if in continuous combined are used regimens perimenopausal women, and therefore this form of treatment should be reserved for postmenopausal women who have experienced their last period at least 6 months previously. The same caveat applies to tibolone, a compound with combined oestrogenic, progestagenic, and androgenic actions; in this case 12 months’ amenorrhoea is recommended before starting treatment. What can be done to help perimenopausal women who have climacteric symptoms but are still menstruating? How
250
3
Can we improve compliance with long-term HRT? Maturitas 1992; 15: 151-58. Staland B. Continuous treatment with natural oestrogens and progestogens. A method to avoid endometrial stimulation. Maturitas
1981; 3: 14-151. MacLennan AH, MacLennan A, Wenzel S, Chambers HM, Eckert K. Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial. Med J Aust 1993;159: 10206. 5 Hawthorn RJS, Spowart K, Walsh D, McKay Hart D. The endometrial status of women on long term continuous combined hormone replacement therapy. Br J Obstet Gynaecol 1991; 98: 939-42. 6 Christiansen C, Riis BJ. Five years with continuous combined oestrogen/progestogen therapy: effects on calcium metabolism, lipoproteins, and bleeding pattern. Br J Obstet Gynaecol 1990; 97: 1087-92. 7 Rees MCP, Barlow DH. Quantitation of hormone replacement induced withdrawal bleeds. Br J Obstet Gynaecol 1991; 98: 106-07. 8 Sporrong T, Rybo G, Mattson LA, Vilbergson G, Crona N. An objective and subjective assessment of uterine blood loss in postmenopausal women on hormone replacement therapy. Br J Obstet Gynaecol 1992; 99: 399-401. 9 Hallberg L, Hogdahl AM, Nilsson I, Rybo G. Menstrual blood loss: a population study. Acta Obstet Gynecol Scand 1966; 45: 320-51. 10 Anderson K, Mattson LA, Rybo G, Stadberg E. Intrauterine release of levonorgestrel: a new way of adding progestogen in hormone replacement therapy. Obstet Gynecol 1992; 79: 963-67. 4