Guest Post by Jerilynn Prior, M.D.,  Centre for Menstrual Cycle and Ovulation Research

Yes! I’m sure you can hear my whoop of excitement and vindication. Finally, something negative about estrogen and positive about progesterone in the mainstream media. According to this article by Emily Anthes in the current issue of Scientific American: Mind,  women’s risk for addiction, and potential for successful withdrawal, are both linked to our menstrual cycle hormones. Estrogen increases women’s addictive behaviors while progesterone assists with successful addiction recovery.

Why am I feeling vindicated? Because I recently declared that hot flushes/flashes and night sweats are estrogen addiction (1). That wild but supportable hypothesis is based on the evidence that prolonged or high-dose estrogen exposure is required for hot flushes to occur. But, it is the subsequent abrupt decrease in estrogen levels that triggers vasomotor symptoms. Drug exposure—drug withdrawal symptoms. And do women feel high on estrogen? Perhaps. Clearly the withdrawal is miserable—as one woman said, “I continued to take it only because I couldn’t stand being off the hormone. I really couldn’t function.” (p. 2130 (2). Just ask any woman taking estrogen for hot flushes who has tried to stop it.

Rat brains are not the focus of my research—and I generally think rodents aren’t much like women. However, the animal evidence showing that estrogen increases addictive behaviours is strong and extensive. About a year ago I had occasion to visit a recovery facility for women with addictions—it suddenly struck me that most of the women there were perimenopausal. They were experiencing estrogen’s highs and the roller coasters and because normal ovulation is rare in perimenopause they were not having enough progesterone—and battling drug dependence. Sure enough, as Anthes states, hundred of experiments show that female rats become addicted more quickly than male rats, are less likely to become addicted without their ovaries but the quick-dependence problem returns when they are given estrogen (3).

As Anthes reports, it is exciting from animal data that progesterone assists to prevent or treat addictions. However, even more important is the notion that progesterone can assist in addiction recovery—not just in rats but in women. The data strongly suggest that progesterone aids women trying to stop cigarettes (4). Progesterone also appears to decrease the drug “high,” and certain actions of cocaine such as fast heart rate in women who are addicted (5). That was true whether cocaine was administered in the luteal phase (when progesterone is normally high) compared with the estrogen-dominant follicular phase, or when progesterone or placebo were administered to women in the follicular phase (5).

The effect of stress can add another layer of understanding to the addiction arena. We know that estrogen amplifies the responses of the stress hormones ACTH, cortisol and norepinephrine to social stress (ironically, based on a randomized, placebo-controlled trial in men) (6). Could that be one of the reasons estrogen increases women’s addiction susceptibility? It is known but rarely discussed that stress makes both addictive behaviors and hot flushes worse. Progesterone’s positive role in both addictions and hot flush treatment may be because of its effects to improve sleep and decrease anxiety. Two different randomized, placebo-controlled, double masked (neither researchers nor participants knew the identity of the pills) trials show that oral micronized progesterone (Prometrium—300 mg at bedtime) improves sleep without a morning hangover (7), and decreases anxiety in women with premenstrual symptoms (8). These actions may play important roles in progesterone’s potential use as a treatment for addictions and for hot flushes.

I’m happy to see this recent review of women and addictions—in addition to being a fact-based exception to the “good-news-estrogen-tune” that the media usually sings, the evidence that progesterone might help women with addictions toward successfully withdrawal is fundamentally good news. Finally, these differing brain-centered actions of progesterone and estrogen fit with the Susan Baxter’s and my message that for good health our two important hormones need to be in balance—the theme of our recent book, The Estrogen Errors—Why Progesterone is Better for Women’s Health (Praeger, Westport, CT 2009)(9).

Cross-posted at The Estrogen Errors.

Want to help? If you are a woman who has diary data of hot flushes/night sweats before, during and after stopping estrogen, we at CeMCOR would love to talk with you (cemcor@interchange.ubc.ca). These data aren’t captured in the published estrogen-hot flush trials but could be very important for women’s decisions about whether to take estrogen or medroxyprogesterone for hot flush treatment—we have shown that they are equally effective (10). We have recently documented the progesterone and placebo withdrawal experiences of women in a hot flush trial.

References

1. Prior JC. Hot flush pathophysiology predicts prevention and treatment – a model of estrogen addiction with progesterone-facilitated withdrawal. J Women’s Health 19, 629. 2010.
2. Grady D. A 60-year-old woman trying to discontinue hormone replacement therapy. JAMA 2002; 287:2130-2137.
3. Larson EB, Anker JJ, Gliddon LA, Fons KS, Carroll ME. Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access. Exp Clin Psychopharmacol 2007; 15(5):461-471.
4. Allen SS, Allen AM, Pomerleau CS. Influence of phase-related variability in premenstrual symptomatology, mood, smoking withdrawal,
   and smoking behavior during ad libitum smoking, on smoking cessation outcome. Addict Behav 2009;
   34(1):107-111.
5. Evans SM, Foltin RW. Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men. Neuropsychopharmacology 2006; 31(3):659-674.
6. Kirschbaum C, Schommer N, Federenko I, Gaab J, Neumann O, Oellers M et al. Short-term estradiol
   treatment enhances pituitary-adrenal axis and sympathetic responses to psyhosocial stress in healthy
   young men. J Clin Endocrinol Metab 1996; 81:3639-3643.
7. Schussler P, Kluge M, Yassouridis A, Dresler M, Held K, Zihl J et al. Progesterone reduces wakefulness in sleep EEG and has no effect on
   cognition in healthy postmenopausal women. Psychoneuroendocr 2008; 33(8):1124-1131.
8. Dennerstein L, Spencer-Gardner C, Gotts G, Brown JB, Smith MA. Progesterone and the premenstrual syndrome: a double blind crossover trial. Br Med J 1985; 290:1617-1621.
9. Baxter S, Prior JC. The Estrogen Errors: Why Progesterone is Better For Women’s Health. Westport: Praeger Publishers,
   2009.
10. Prior JC, Nielsen JD, Hitchcock CL, Williams LA, Vigna YM, Dean CB. Medroxyprogesterone and conjugated oestrogen are equivalent for hot flushes: a 1-year randomized double-blind trial following premenopausal ovariectomy. Clin Sci (Lond) 2007; 112(10):517-525.