Blog of the Society for Menstrual Cycle Research

Hooked on Estrogen

May 13th, 2010 by Elizabeth Kissling

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

Estrogen moleculeYes! 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.

  

4 Responses to “Hooked on Estrogen”

  1. Liberality says:

    From my own experience I began menopause at 39 years of age. I had not been on
    the pill or using any form of hormones but the hot flashes were so bad that I
    quickly began a hormone treatment. I have gone off hormones twice now, (I’m 46 and
    will turn 47 this autumn), and each time I became so miserable that I returned to
    using hormones once again. The flashes are bad enough but it’s the lack of sleep,
    the itchiness, and diminished sex drive, and brain fog that truly make me feel crazy.
    I take progesterone, since I still have my uterus, but I hate it more than the
    estrogen. Progesterone makes me weepy, bloated, and crave chocolate–not a state of
    being I like necessarily.

  2. Laura Wershler says:

    Liberality, I hope Jerilynn Prior will respond to your comment. There is a better treatment option than the one you are on.

  3. This is so fascinating – a whole new way of thinking about women and addiction. I’m thinking back to the early pill – the mix of alcohol (in private) and then getting “tranquilizers” from the doctor, and then add in the first oral contraceptives – like there’s a whole cohort of women from back in the 70s charting unexplored addictive territory – and taking their kids along for the ride, in some cases…

    I’m also fascinated that the menstrual “monologue” in Vagina Monologues was not really a monologue at all, but, as Irralie Doel pointed out (in a paper she presented at Liverpool Blood, Body, Brand conference), was just a string of separate one-liners, “snippets” – not a fully-formed narrative like the other monologues.

    Ensler has stated in interviews that she had a drinking problem as a young woman…I can’t imagine, if she was having regular menstrual cycles (Ensler hasn’t said) in the midst of the drinking crazies / possible PTSD, that her cycles were too enjoyable…

    …I guess what I’m getting at is, it’s fascinating how scientific research and empirical data open up new ways for writers, filmmakers, etc., to create new, and hopefully more accurate, narratives of women’s experiences…maybe The Vagina Monologues should have been named The Estrogen-Progesterone Dialogues? :)

  4. Hello Liberality,
    I don’t blame you at all for being unhappy feeling “weepy, bloated, and crave chocolate.” It seems likely to me, however, that it is the combination of the estrogen and the progestin/progesterone you are on that are causing those negative experiences, not the progesterone.

    I suspect that you are taking a pill form of estrogen and in a 100% or higher dose (like 0.625 mg of Premarin or 2 mg of Estrace) and that you are on a low dose, and probably cyclic form of synthetic progesterone, a progestin (like 5 mg of medroxyprogesterone) for part of the month.

    There are better approaches to dealing with coming to menopause too early. If you look at the CeMCOR website http://www.cemcor.ubc.ca/help_yourself/articles/oht_early_menopause you’ll find a different approach to treatment of menopause that comes at a young age. I think that estrogen should always be given in a patch or gel or cream form (to lessen the risk for blood clots and because this is the more physiologic therapy) and that the molecularly identical form of progesterone (Prometrium) is ideal.

    Prometrium does not cause those problems in trials in which it is given alone (not with estrogen) and also not when it is given with transdermal estrogen (although that has been less well studied). The dose of progesterone that you need to help your sleep as well as to control your hot flushes is 300 mg taken just before you sleep at night. (Prometrium is expensive–if you cannot afford it, once you are on transdermal estrogen I think you would be fine on the less expensive medroxyprogesterone 10 mg/day.) A randomized blinded controlled trial shows that when combined with the estrogen patch, medroxyprogesterone does not cause mood or other side effects.

    Once you have a combination of bio-identical hormones that feels good for you, because you came up short of the good things that having estradiol and progesterone do for your body, I’d suggest you continue both until you are 50 or 51. The risks shown for women with menopause at a normal age who take more hormones later are not true for someone in your circumstance.

    When you are 51 and want to stop estrogen, I’d be sure to start or continue Prometrium in a 300 mg dose and follow the instructions on the CeMCOR website for stopping estrogen therapy http://www.cemcor.ubc.ca/help_yourself/articles/stopping_estrogen. You can decrease the estrogen dose as slowly as you need and eventually end up having progesterone control your hot flushes/flashes, give you a better sleep and eventually find yourself no longer addicted to estrogen.

    Hope this is helpful for you,
    All the best,
    Jerilynn

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