More confusion about perimenopause—author responds

Issue: BCMJ, vol. 48, No. 6, July August 2006, Pages 256-257 Letters
By: Jerilynn C. Prior, MD, FRCPC

In his recent letter (BCMJ 2006;48:66), Dr Timothy Rowe took issue with my assessment of results of the controlled trial of a 20 µ-ethinyl estradiol oral contraceptive (OC) in perimenopause.[1] I stand by what I said: therapy with OC in perimenopausal women does not significantly improve hot flushes or quality of life.[2]

Dr Rowe correctly recalls the article’s figures but has forgotten the scientific comparison of change on OC with change on placebo. The 50% hot flush “differences were not statistically significant.” (p. 143)[1] Likewise, “There were no significant between-group differences in the endpoint quality of life scores.” (p. 145)[1]

I share Dr Rowe’s concern about the lack of randomized placebo-controlled trial data of oral micronized progesterone as a therapy for symptomatic perimenopausal women. Except for one trial showing the effectiveness of cyclic progesterone for premenstrual symptoms using a double blind placebo-controlled cross-over design,[3] controlled trials are lacking. The lack of evidence does not negate the science documenting that perimenopause is a time when estrogens average 30% higher and are not reliably suppressed by exogenous estrogen[4,5] and progesterone is significantly lower[4,6] than in premenopausal women. Given the less-than-satisfactory scientific results of the Casper trial,[1] does progesterone therapy not make more physiological sense for perimenopausal treatment than the supraphysiological estrogen and androgenic progestin of oral contraceptives?

Thanks, Dr Murray Allen, for lauding our “attempts to proffer some sense to the confusion surrounding perimenopause” (BCMJ 2005;47:66). Sorry we failed to “excite” you and to recommend “the king of the female replacement hormones, testosterone.” Again, relying on physiology to direct therapy, we would not use testosterone because there is no significant decrease in free androgen levels in perimenopause.[7] Perimenopausal women are not using the Daily Perimenopause Diary[8] to “tabulate their grief” but to feel some control over the difficult symptoms of perimenopause that get better in (untreated) menopausal women.[9]

—Jerilynn C. Prior, MD, FRCPC
Centre for Menstrual Cycle and Ovulation Research, 
Division of Endocrinology, UBC

References

1. Casper RF, Dodin S, Reid RL, Study Investigators. The effect of 20 µg ethinyl estradiol/1 mg norethindrone acetate (Minestrin), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997;4:139-147. 
2. Prior JC. Clearing confusion about perimenopause. BCMJ 2005;47:538-542. Full Text 
3. Dennerstein L, Spencer-Gardner C, Gotts G, et al. Progesterone and the premenstrual syndrome: A double blind crossover trial. BMJ 1985;290:1617-1621. PubMed Abstract 
4. Santoro N, Rosenberg J, Adel T, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab 1996;81:4,1495-1501. PubMed Abstract 
5. Prior JC. Perimenopause: The complex endocrinology of the menopausal transition. Endocr Rev 1998;19:397-428. PubMed Citation Full Text 
6. Prior JC. The ageing female reproductive axis II: Ovulatory changes with perimenopause. In: Chadwick DJ, Goode JA. (eds). Endocrine Facets of Ageing. Chichester, UK: John Wiley and Sons Ltd; 2002. 172-186 pp. 
7. Burger HG, Dudley EC, Cui J, et al. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab 2000;85:2832-2838. Full Text 
8. Hale GE, Hitchcock CL, Williams LA, et al. Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life women: Information collected using the Daily Perimenopause Diary. Climacteric 2003;6:128-139. PubMed Abstract Full Text 
9. Neugarten BL, Kraines RJ. Menopausal symptoms in women of various ages. Psychomatic Med 1965;27:266-273. PubMed Citation 

Jerilynn C. Prior, MD, FRCPC. More confusion about perimenopause—author responds. BCMJ, Vol. 48, No. 6, July, August, 2006, Page(s) 256-257 - Letters.


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