Perimenopause and Menopause As Oestrogen Deficiency While Ignoring

CORRESPONDENCE LINK TO ORIGINAL ARTICLE LINK TO AUTHORS’ REPLY

medroxyprogesterone14, or oral micronized progesterone alone15. However, I challenge Perimenopause and menopause the authors to provide data from randomized controlled trials in perimenopausal women as oestrogen deficiency while showing that oestrogen therapy decreases vasomotor symptoms more than placebo. ignoring progesterone The Primer puts forward a version of these normal and universal life phases in women as ‘oestrogen deficiency’, but this is a Jerilynn C. Prior decades’ old, non-physiological perspective.

In their recent Primer article (Menopause. In addition, there is a persistent, non- Jerilynn C. Prior is at the Centre for Menstrual Cycle 1 and Ovulation Research, University of British Nat. Rev. Dis. Primers 1, 15004 (2015)) , scientific conflation of perimenopause and Columbia, Vancouver Coastal Health Research Susan Davis and colleagues describe the life menopause, their symptoms (ambiguously Institute, Gordon and Leslie Diamond Centre, phases that every woman (surviving long called ‘menopausal symptoms’) and their Room 4111, 2775 Laurel Street, Vancouver, enough) will experience. However, they do therapies. If discussing perimenopausal British Columbia V5Z 1M9, Canada. [email protected] not include in their description the evidence symptoms, menometrorrhagia4,5, mastalgia6, 7 that the ‘cause’ of menopause (oestrogen headaches and nausea should take centre doi:10.1038/nrdp.2015.31 loss), related to the key hormonal and other stage. These two life phases do share hot 1. Davis, S. R. et al. Menopause. Nat. Rev. Dis. Primers changes of perimenopause and menopause, flushes and night sweats (that is, vasomotor 1, 15004 (2015). disappears when ageing and socioeconomic, symptoms), and vaginal dryness; although 2. Lock, M. Contested meanings of the menopause. Lancet 337, 1270–1272 (1991). lifestyle, genetic, racial and cultural factors vaginal dryness occurs in perimenopause 3. Nielsen, H. K., Brixen, K., Bouillon, R. & Mosekilde, L. are taken into account2. for unknown reasons. However, hormonally, Changes in biochemical markers of osteoblastic activity during the menstrual cycle. J. Clin. Endocrinol. The pleomorphic experience changes perimenopause and menopause are as Metab. 70, 1431–1437 (1990). that women describe, especially in peri- different as chalk and cheese. Compared with 4. Kaufert, P. A. Menstruation and menstrual change: women in midlife. Health Care Women Int. 7, 63–76 menopause, often do become symptomatic, premenopausal women, oestrogen levels are (1986). causing women to seek medical attention. erratically higher in perimenopause8 and 5. Moen, M. H., Kahn, H., Bjerve, K. S. & Halvorsen, T. B. Menometrorrhagia in the perimenopause is However, the pervasive medicalization of stably lower in menopause; progesterone associated with increased serum estradiol. Maturitas perimenopause and menopause is related levels silently decline and become lower in 47, 151–155 (2004). 6. Dennerstein, L., Dudley, E. C., Hopper, J. L., to a lack of accurate, woman-centred the perimenopausal years before the last Guthrie, J. R. & Burger, H. G. A prospective information; the concept (alive and well flow9. In contrast to conventional wisdom10, population-based study of menopausal symptoms. Obstet. Gynecol. 96, 351–358 (2000). in this Primer) that menopause means perimenopause begins with changes in 7. Prior, J. C. Estrogen’s Storm Season. Stories of ‘oestrogen loss’ and ‘oestrogen deficiency’ experiences within regular cycles at a time Perimenopause (CeMCOR, 2007). (REF. 1) 8. Prior, J. C. Perimenopause: the complex endocrinology is the height of misinformation given when oestrogen levels are already higher of the menopausal transition. Endocr. Rev. 19, that this is a normal life phase. The authors and progesterone levels already lower than 397–428 (1998). 11 9. Hale, G. E. et al. Endocrine features of menstrual do admit that perimenopause is associated in premenopause . cycles in middle and late reproductive age and the with higher than normal oestrogen levels1. Vasomotor symptoms, which are a key menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) In a physiological context, changes in adverse experience of both perimenopause staging system. J. Clin. Endocrinol. Metab. 92, oestrogen levels during menopause must and menopause, are discussed in a way 3060–3067 (2007). 10. Harlow, S. D. et al. Executive summary of the Stages be considered in conjunction with the that creates confusion, includes no primary of Reproductive Aging Workshop +10: addressing the concomitant decreases in progesterone physiological references and alludes to the unfinished agenda of staging reproductive aging. J. Clin. Endocrinol. Metab. 15, 105–114 (2012). levels, which are more pronounced than any old hypothesis that low oestrogen levels 11. Prior, J. C. Clearing confusion about perimenopause. decreases in oestrogen levels. Why? With cause these symptoms12. Why, then, do BCMJ 47, 538–542 (2005). 12. Miller, H. G. & Li, R. M. Measuring hot flashes: the menstrual cycle as the gold standard, perimenopausal women experience vaso summary of a National Institutes of Health workshop. oestradiol levels are measured in picomoles, motor symptoms when they ‘have rather Mayo Clin. Proc. 79, 777–781 (2004). (REF. 1) 13. MacLennan, A. H., Broadbent, J. L., Lester, S. & whereas progesterone levels are in the high levels of oestrogens’ ? The authors Moore, V. Oral oestrogen and combined oestrogen/ nanomolar range; in percentage terms, from state that: “Hypothalamic insensitivity to progestogen therapy versus placebo for hot flushes. Cochrane Database Syst. Rev. 18, CD002978 (2004). cycle day 1, oestradiol levels rise 225% to its oestrogens also explains why menopausal 14. Prior, J. C. et al. Medroxyprogesterone and mid-cycle peak, but ovulatory progesterone symptoms — such as hot flushes and night conjugated oestrogen are equivalent for hot flushes: a 1‑year randomized double-blind trial following levels rise 1,400% to its luteal-phase plateau sweats — commonly occur at this stage premenopausal ovariectomy. Clin. Sci. (Lond.) 112, (admittedly, for only 10–16 days of the [perimenopause]… as well as why exogenous 517–525 (2007). 3 15. Hitchcock, C. L. & Prior, J. C. Oral micronized average ovulatory cycle) . In this Primer, oestrogens are effective in reducing the progesterone for vasomotor symptoms — a placebo- discussion of progesterone, the second main symptoms” (REF. 1). Randomized controlled controlled randomized trial in healthy postmenopausal gonadal steroid in women, is virtually non- trials have shown that menopausal vaso women. Menopause 19, 886–893 (2012). existent; it is even missing from a diagram of motor symptoms are effectively treated Competing interests menstrual cycle hormones1. by oestrogen or oestrogen–progestin13, The author declares no competing interests.

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