18 May, 2015:

The average age of menopause in women in the Western world is 51 years. Women who experience menopause between the ages of 40 and 45 years have what has been called 'early menopause', which is reported to occur in approximately 5% of women [1, 2]. These women, with a premature decrease of estrogen production, seem to have an increased risk of overall mortality and morbidity [2–5]. However, to our knowledge, only a few studies have been published on the benefits from long-term hormone therapy (HT) in this population [4,6].

According to the standard recommendations, HT should be given to women at premature or early menopause and should be continued at least to age 51–52 years, the average age of menopause in Shuster's study population (Mayo Clinic Olmsted County, Minnesota) [2].

In Sweden, the use of HT in 47–56-year-old women was approximately 6% (data from the Swedish Prescribed Drug Registry 2010–2012), which we consider to be an underutilization of HT when considering the prevalence of symptoms in this age group. We also suspected that the underutilization would be even more pronounced in women aged 40–44 years.

The aim was to determine the number of current and new HT users and the duration of HT use in Swedish women aged 40–44 years with probable early menopause during a 5-year period (July 2005–December 2011).

The study population consisted of all women, nationally registered in Sweden, who were 40–44 years old on 31 December 2005 (n = 310,404). These women and their HT use were followed from 1 July 2005 until 31 December 2011. Of these women, 5.9% (n = 18,184) had HT dispensed at least on one occasion between 1 July 2005 and 31 December 2011, 4.3% (n = 13,229) had been dispensed twice and 3.5% (n = 10,984) three times. Only 1% of the women were current users when the study started. About 0.9% of women 40–44 years old started HT during the study period and the majority discontinued HT within 1 year; median duration of HT use was 308 days (25th–75th percentile 1059–120 days; mean 598 days) At the end of the study period, only about one-fifth (n = 487) of women under 45 years at start of HT still used HT.

Comment

The prescription of HT for menopausal symptoms has changed dramatically in many countries including Sweden over the last few decades, probably due to the results from the Million Women Study, the Heart and Estrogen/progestin Replacement Study and the Women's Health Initiative [7-10]. The use of HT, at least in Sweden, still seems to be questioned by both women and physicians, since only approximately 6% of women aged 47–56 years use HT, according to data from the Swedish Prescribed Drug Registry 2010–2012. We assume that there is still an unwarranted fear of long-term effects of HT based on earlier alarm reports. It is also possible that the women met practitioners that are not up-to-date in this issue and that HT may be discontinued because of fear of long-term adverse events of HT. Perhaps at least some of the women do not perceive vasomotor symptoms and therefore stop treatment because of the absence of symptoms.

However, we can only estimate the incidence of early menopause in Swedish women by comparison with the rate from other studies in other countries [1,2]. As the occurrence of spontaneous early menopause in women age 40–45 years is reported to be about 5% [2], the fact that less than 2% of Swedish women age 40–44 are treated with HT during at least a part of the age interval suggests a too low treatment rate. Guidelines concerning early menopause or premature menopause have been developed by The Medical Products Agency of Sweden and recommend that these women should be treated with HT up to age 50. The Agency also states that the risk versus benefit calculation for HT assessment is probably not the same for women with early menopause as for postmenopausal women, indicating that individual assessment for every woman is necessary. It may be that some women with early menopause are treated with combined oral contraceptives. We found, however, that less than 1% of women in the same study were new users of combined oral contraceptives during the time interval and probably most of them did not start therapy due to early menopause but because of need of contraception.

In conclusion, the results from this study point to an underutilization of HT in Swedish women with assumed early menopause. It also shows that, in spite of recommendations from The Medical Products Agency of Sweden, many women discontinue their treatment prematurely. We can only speculate on the causes for this, but believe that there is still a fear of side-effects from HT and probably the benefits of HT in women with premature or early menopause are not well known.

Mats Hammar, Anna-Clara Spetz Holm and Lotta Lindh-Åstrand
Division of Obstetrics and Gynaecology, Department of Clinical and Experimental Medicine, Linköping University, County Council of Östergötland, Linköping, Sweden
and
Mikael Hoffmann
The NEPI foundation, Division of Health Care Analysis, Department of Medicine and Health, Linköping University, Linköping, Sweden
and
Mats Fredriksson
Division of Occupational and Environmental Medicine, Department of Clinical and Experimental Medicine and Linköping Academic Research Center, Faculty of Health Sciences, Linköping University, Sweden

References

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http://www.ncbi.nlm.nih.gov/pubmed/3960433 

2. Shuster LT, Rhodes DJ, Gostout BS, Grossardt BR, Rocca WA. Premature menopause or early menopause: long-term health consequences. Maturitas 2010;65:161-6
http://www.ncbi.nlm.nih.gov/pubmed/19733988 

3. Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas 2006;53:226-33
http://www.ncbi.nlm.nih.gov/pubmed/15955642 

4. Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009;16:15-23
http://www.ncbi.nlm.nih.gov/pubmed/19034050 

5. Rivera CM, Grossardt BR, Rhodes DJ, Rocca WA. Increased mortality for neurological and mental diseases following early bilateral oophorectomy. Neuroepidemiology 2009;33:32-40
http://www.ncbi.nlm.nih.gov/pubmed/19365140 

6. Popat VB, Calis KA, Kalantaridou SN, et al. Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement. J Clin Endocrinol Metab 2014;99:3418-26
http://www.ncbi.nlm.nih.gov/pubmed/24905063 

7. Beral V, Million Women Study C. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419-27
http://www.ncbi.nlm.nih.gov/pubmed/12927427 

8. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605-13
http://www.ncbi.nlm.nih.gov/pubmed/9718051 

9. Rossouw JE, Anderson GL, Prentice RL, et al. 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
http://www.ncbi.nlm.nih.gov/pubmed/12117397 

10. Hoffmann M, Hammar M, Kjellgren KI, Lindh-Åstrand L, Brynhildsen J. Changes in women's attitudes towards and use of hormone therapy after HERS and WHI. Maturitas 2005;52:11-17
http://www.ncbi.nlm.nih.gov/pubmed/16023804