Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7419.845 (Published 09 October 2003) Cite this as: BMJ 2003;327:845All rapid responses
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We believe the survey by Lawton, Rose, McLeod and Dowell1 gives an
overestimate of the true numbers of women that stopped taking HRT due to
recent study findings2 and consequent media coverage.
The 998 women surveyed were all women who were ineligible or
unwilling to join the international WISDOM study. This makes them a very
unusual subset of women on HRT probably not representative of the group as
a whole. These women may have been unwilling to join the WISDOM study
because they were unsure if they wanted to take HRT long term. If this is
the case the fact that 58% of them stopped taking HRT when risks became
more apparent to them is unsurprising. Ultimately the reasons these 998
women were unwilling or ineligible to take part in the WISDOM study was
not elucidated and it is of great importance in assessing whether this
sample is at all representative of women on HRT in general. We believe the
unusual criteria for selection has led to the selection of a non-
representative group and has created selection bias in this survey.
As noted in the article the 19% who were non – responders were
generally people who had used HRT for less than 5 years. Furthermore the
survey also found that of the responders there was a statistically
significant decreased rate of HRT cessation in women who had been using
HRT for less than 5 years. So it is not only possible but likely that that
the 19% who did not respond had a lower rate of cessation that the
responders. This second source of selection bias is also likely to have
contributed to an overestimate.
The effect of the recent findings and media coverage concerning HRT
side effects could have been more accurately assessed by performing a
study with a similar design to Marata et al3. By evaluating data on
prescriptions and expenditure on HRT before and after the recent events
would not only provide more accurate data than a survey but it would
potentially provide information about the entire HRT using population in
New Zealand. A study of this kind would not be able to assess the reasons
for cessation of HRT nor the characteristics of women who were more likely
to stop but it would provide a very accurate measure of the decrease in
HRT usage.
References:
1. Beverley Lawton, Sally Rose, Deborah McLeod, and Anthony Dowell
Changes in use of hormone replacement therapy after the report from the
Women's Health Initiative: cross sectional survey of users BMJ 2003; 327:
845-846
2. Writing Group for the Women's Health Initiative Investigators.
Risks and benefits of estrogen plus progestin in healthy postmenopausal
women. Principal results from the Women's Health Initiative randomised
controlled trial. JAMA 2002;288: 321-33
3. Changes in Italy after the WHI study: the fishing out of tibolone
Anna Maria Marata, Susanna Maltoni, Angelo Menna, Vittorio Basevi, Antonio
Addis, and Nicola Magrini 24 Oct 2003.
Competing interests:
None declared
Competing interests: No competing interests
The cohort of Lawton’s study answered the question about physicians’
and patients’ attitudes towards hormone replacement therapy (HRT) after
Women Health Initiatives (WHI) study[1]: an overall 18% decrease in HRT
has been recently observed in New Zealand.[2]
Taking advantage of data coming from the Italian Drug Monitoring
Centre (OsMed)[3] we investigated if a similar behaviour was confirmed
also in Italy. Analysis on both prescriptions (expressed as DDD per 1,000
persons per day) and expenditure (expressed as € per person per day) for
oestrogenic and progestogenic drugs was performed. In particular, we
compared the figures referred to the first semester 2002 to those for the
first semester 2003 (OsMed, data to be published).[3]
Oestrogens showed a decrease both in prescriptions and in
expenditure (-18% and –27%, respectively) whereas for progestins we
observed a 7% decrease in DDDs and a 7% increase in expenditure.
Performing a more detailed analysis on progestins we found that all the
drugs but one (i.e. tibolone) registered a relevant decrease in
prescription (from –9% for progesterone to –64% for medroxyprogesterone).
Tibolone prescription increased enormously, approximately by 38%;
among HRT drugs, its expenditure has reached the second place, with
estradiol ranking first.
Tibolone is classified as a progestin but it also has estrogenic and
androgenic properties.[4] It has been used in Europe for almost 2 decades
and in Italy it is fully reimbursed by the National Health System since
December 2001 for treatment of “climateric syndrome and prevention of
postmenopausal osteoporosis”. We question the shift towards a drug,
tibolone, which lacks data from RCTs showing its effectiveness (or harms)
based on clinical end-points (fractures, myocardial infarction, breast
cancer or other events)[4] and not surrogated ones.
Since ten years ago, Italian National Health System was strongly at
odds with nasal calcitonin (ranking first in drug expenditure),[5] we
wonder whether tibolone is going to become another controversial issue.
1. Writing Group for the Women’s Health Initiati-ve Investigators.
Risks and benefits of estrogen plus progestin in healthy postmenopausal
women: principal results from the Women’s Health Initiative randomized
controlled trial. JAMA 2002; 288:321-33
2. Lawton B, Rose S, McLeod D, Dowell A. Changes in use of hormone
replacement therapy after the report from the Women's Health Initiative:
cross sectional survey of users. BMJ 2003;327:845-6
3.
wttp://www.ministerosalute.it/medicinali/osmed/sezApprofondimenti.jsp?label=rap
4. Modelska K, Cummings S. Tibolone for postmenopausal women:
systematic review of randomized trials. J Clin Endocrinol Metab. 2002
Jan;87(1):16-23
5. Magrini N, Vaccheri A, Montanaro N. The Italian way of
osteoporosis. Lancet. 1992;39:499-500
Competing interests:
None declared
Competing interests: No competing interests
That's what I feel is the saddest thing to come out of WHI. We have
a whole lot of rather negative - or less positive - data, derived from the
above, but derived from a substantive cohort which is not directly
comparable with the group who we know, or thought we knew, benefitted most
from early HRT. That is the younger woman just entering the menopause.
I'm still having trouble reconciling what this study purports to
show, when it is so different from my personal experience in practice,
especially when the cohort was so predominently elderly and obese, many
having had pre-existing conditions, and most of which had already lost
valuable preventative intervention time.
The other sad thing about it all was the abandonment of other more
relevant studies, and medico-legal rough pineapple it would now be to try
and re-do this study, putting the same questions to a more appropriate
group.
As I stated at above, the net effect has been to basically take us
back into what I consider to be the 'dark ages' with repect to what we can
now (medico-legally) safely offer our patients to see them through this
phase of their life, which many find quite harrowing, and the potential
loss of opportunity to do something other than just 'damage control' with
respect to many of the accelerated degenerative conditions we all witness
speed up after the menopause. I'm afraid red clovers, wild yams, black
cohosh or evening primroses just don't cut it. I'm afraid it will be
scant comfort to be able to say "we told you so", when in a few years
time, the surge in many of these potentially preventable conditions proves
what I suspect they will prove. Then what? Start all over again?
Peter Bradley
GP, Brisbane, Australia
Competing interests:
None declared
Competing interests: No competing interests
One thing they did not ask is the reason for taking HRT. If the woman
was taking it for osteoporosis, they might be less likely to stop. In
practices in this office, the longer a woman is on it, the older she is,
the less likely she was to stop. I'd like to see a larger group.
Competing interests:
I edited a book on Women's health (Cambridge University Press)
Competing interests: No competing interests
Re: Changes in use of hormone replacement therapy after the report from the Women's Health Initiative: cross sectional survey of users
Dear Editors,
Tibolone prevents postmenopausal bone loss and osteoporotic fractures better than raloxifene, as effectively as estrogens. [1][2][7]
Tibolone does not increase the risk of myocardial infarction. Indeed, it could have a beneficial effect. [3][7]
Tibolone reduces blood pressure, inflammation and glycaemia without worsening oxidative stress. [9]
Tibolone does not increase the risks for thromboembolic events or endometrial cancer. In fact, tibolone influences coagulatory factors in menopause promoting fibrinolisis, even better than estradiol. [4][13]
Tibolone reduces the incidence of primary breast cancer and the risk for invasive breast cancer. [2][4]
Tibolone reduces visceral fat. [5][10]
Tibolone improves almost all hearing threshold levels. [6]
Tibolone relieves climacteric symptoms, improves mood, improves sexual well-being (desire, arousal and orgasm domains), health-related quality of life. [7][8][11]
Tibolone also has in vitro antiproliferative effects! [12]
References
[1] Osteoporos Int. 2008 Aug;19(8):1153-60. Epub 2008 Feb 7.
Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women.
Delmas PD, Davis SR, Hensen J, Adami S, van Os S, Nijland EA.
INSERM Research Unit 831 and University of Lyon, Lyon, France.
http://www.ncbi.nlm.nih.gov/pubmed/18256777
[2] N Engl J Med. 2008 Aug 14;359(7):697-708.
The effects of tibolone in older postmenopausal women.
Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, Kloosterboer L, Mosca L, Christiansen C, Bilezikian J, Kerzberg EM, Johnson S, Zanchetta J, Grobbee DE, Seifert W, Eastell R; LIFT Trial Investigators.
San Francisco Coordinating Center and the California Pacific Medical Center Research Institute, San Francisco, USA.
http://www.ncbi.nlm.nih.gov/pubmed/18703472
[3] Eur Heart J. 2008 Nov;29(21):2660-8. Epub 2008 Sep 30.
Hormone therapy and risk of myocardial infarction: a national register study.
Lokkegaard E, Andreasen AH, Jacobsen RK, Nielsen LH, Agger C, Lidegaard .
Gynaecological Clinic, Rigshospitalet, Copenhagen , Denmark.
http://www.ncbi.nlm.nih.gov/pubmed/18826989
[4] Ann Intern Med. 2009 Nov 17;151(10):703-15, W-226-35.
Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer.
Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L.
Oregon Health & Science University, Veterans Affairs Medical Center, Portland, OR 97239-3098, USA.
http://www.ncbi.nlm.nih.gov/pubmed/19920271
[5] Int J Gynaecol Obstet. 2011 Nov;115(2):191-3. Epub 2011 Aug 27.
Visceral adiposity after tibolone use.
Carranza-Lira S, Barcena-Jacobo TD, Sandoval-Barraqan MP, Ramos-Leon JC.
Gynecology and Obstetrics Hospital Luis Castelazo Ayala, Social Security Mexican Institute, Mexico City, Mexico.
http://www.ncbi.nlm.nih.gov/pubmed/21872859
[6] Climacteric. 2011 Apr;14(2):262-7. Epub 2010 Aug 7.
Effect of tibolone on audiologic functions in menopausal women.
Kosus N, Kosus A, Turhan NO, Kurtaran H.
Department of Obstetrics & Gynecology, Faculty of Medicine, Fatih University, Ankara, Turkey.
http://www.ncbi.nlm.nih.gov/pubmed/20690865
[7] Gynecol Endocrinol. 2010 Nov;26(11):804-14.
Tibolone in postmenopausal women: a review based on recent randomised controlled clinical trials.
Biglia N, Maffei S, Lello S, Nappi RE.
Gynecological Oncology Department, University of Turin, Mauriziano Umberto I Hospital, Turin, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/20586550
[8] Int J Gynaecol Obstet. 2010 Sep;110(3):213-6. Epub 2010 Jun 8.
Effects of transdermal estradiol gel and oral tibolone on health-related quality of life after surgical menopause.
Bhattacharya SM, Jha A.
KPC Medical College and Hospital, Kolkata, India.
http://www.ncbi.nlm.nih.gov/pubmed/20570264
[9] Gynecol Endocrinol. 2011 Mar;27(3):163-9. Epub 2010 May 26.
Effects of menopause and tibolone on different cardiovascular biomarkers in healthy women.
Vassalle C, Cicinelli E, Lello S, Mercuri A, Battaglia D, Maffei S.
Fondazione G. Monasterio CNR-Regione Toscana and Institute of Clinical Physiology, CNR, Pisa, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/20500110
[10] Climacteric. 2010 Jun;13(3):249-53.
Comparative effects of continuous combined hormone therapy and tibolone on body composition in postmenopausal women.
Ziaei S, Moaya M, Faghihzadeh S.
Department of Obstetrics & Gynecology, Tarbiat Modares University, Tehran, Iran.
http://www.ncbi.nlm.nih.gov/pubmed/19848555
[11] Climacteric. 2010 Apr;13(2):147-56.
Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women.
Ziaei S, Moghasemi M, Faghihzadeh S.
Departments of Obstetrics & Gynecology, Tarbiat Modares University, Tehran, Iran.
http://www.ncbi.nlm.nih.gov/pubmed/19731119
[12] Neurol Res. 2009 Nov;31(9):923-7. Epub 2009 Jun 15.
The effects of tibolone on the human primary glioblastoma multiforme cell culture and the rat C6 glioma model.
Altinoz MA, Albayrak SB, Karasu A, Sabanci PA, Imer M, Bilir A.
Istanbul University, Istanbul, Turkey.
http://www.ncbi.nlm.nih.gov/pubmed/19531283
[13] Gynecol Obstet Invest. 2009;68(1):33-9. Epub 2009 Apr 7.
Effects of either tibolone or continuous combined transdermal estradiol with medroxyprogesterone acetate on coagulatory factors and lipoprotein(a) in menopause.
Perrone G, Capri O, Galoppi P, Brunelli R, Bevilacqua E, Ceci F, Ciarla MV, Strom R.
Department of Gynecology and Obstetrics, University Sapienza, Rome, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/19349712
Competing interests: No competing interests