Role of Progesterone on Bone Health

Progesterone's bone building effects have long been known in laboratory experiments (Stimulatory effects of estrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro. B A Scheven, C A Damen, N J Hamilton, H J Verhaar, S A Duursma, 1992; also see Steroid hormone receptor expression and action in bone. R Bland, 2000 for a review). Furthermore, progesterone declines long before estrogen (right around the time bone starts to decline) as corpus luteum's progesterone secretion function gets weaker and ovulation starts to fail long before menstruation finally stops. 

• Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system. Georgina E Hale, Xue Zhao, Claude L Hughes, Henry G Burger, David M Robertson, Ian S Fraser, 2007 (Ovulatory cycle FSH, LH and estradiol (E2) levels increased with progression of STRAW stage, and mean luteal phase serum progesterone decreased. Early cycle (ovulatory and anovulatory) inhibin B (INHB) decreased steadily across the STRAW stages and was largely undetectable during elongated ovulatory and anovulatory cycles in the menopause transition.)
• Neuroendocrine physiology of the early and late menopause. Janet E Hall 2004
• Total and Unopposed Estrogen Exposure across Stages of the Transition to Menopause. Kathleen A O'Connor, Rebecca J Ferrell, Eleanor Brindle, Jane Shofer, Darryl J Holman, Rebecca C Miller, Deborah E Schechter, Burton Singer, Maxine Weinstein 2009;
• Progesterone and ovulation across stages of the transition to menopause. Kathleen O'Connor, Rebecca Ferrell, Eleanor Brindle, Benjamin Trumble, Jane Shofer, Darryl Holman, Maxine Weinstein 2009;
• Characterization of reproductive hormonal dynamics in the perimenopause. Santoro N, Brown JR, Adel T, Skurnick JH. 1996).
• Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women during a Nine-Year Period Prior to Menopause. Britt-Marie Landgren, Aila Collins, Giorgy Csemiczky, Henry G Burger, Lyrissa Baksheev, David M Robertson 2004

Fig. 2 is a graph showing typical perimenopause cycle pattern variations including cycles with estrogen rising without corresponding progesterone and/or bleeding.  

 

Figure 2. PDG = progesterone metabolite in urine, E1G = estrogen metabolite in urine. The dark bands on the day axis indicate menstruation bleeding days. Source: Progesterone and ovulation across stages of the transition to menopause. Kathleen O'Connor, Rebecca Ferrell, Eleanor Brindle, Benjamin Trumble, Jane Shofer, Darryl Holman, Maxine Weinstein 2009

 

What does the reduced progesterone do to your bone?

If you look at studies that recorded monthly hormonal status along with bone metabolism status, you can see a clear bone building role of progesterone (Progesterone and bone: a closer link than previously realized. V Seifert-Klauss, M Schmidmayr, E Hobmaier, T Wimmer 2012).

A monthly cycle can be divided into 2 parts: before ovulation (follicular phase) and after ovulation (luteal phase). Progesterone is secreted only after ovulation while estrogen is secreted in both before and after. In terms of presence or absence of the two hormones during the luteal phase (after ovulation) of a monthly cycle, there are 4 possible combinations. The conditions in #2 in the table below are the conditions that cause estrogen dominance and the comparison between #1 and #2 will reveal the role of progesterone in the presence of normal or higher than normal estrogen level.

luteal phase	Progesterone present	Progesterone absent or low
Estrogen present	1. Normal cycle	2. Ovulatory Disturbances (no ovulation or short/weak luteal phases)
Estrogen very low	3. does not happen in naturally occurring condition.	4. skipped cycle or surgical/natural menopause

The researchers have found that in perimenopause women (42% of the cycles did not have ovulation) the bone formation marker BAP increased during the luteal phase of ovulatory cycles with high progesterone levels, but not during anovulatory (no progesterone) cycles. The bone resorption marker pyridinoline decreased during the luteal phase of ovulatory cycles with high progesterone levels and decreased to a lesser extent in anovulatory cycles. In other words, progesterone promotes bone building AND suppresses bone resorption. Naturally, those who maintained normal BMD had more normal ovulatory cycles. For those who lost BMD over the 2 year study period, 42% of the BMD change was correlated with skipped cycles, bone resorption, and cortisol.

Studies on younger women (n = 458, mean age 31 years) demonstrated that BMD increased 0.5% per year in association with normal ovulation, and decreased by 0.7% per year in women with ovulatory disturbances (Progesterone and Bone: Actions Promoting Bone Health in Women. by Vanadin Seifert-Klauss, Jerilynn C Prior 2010: meta-analysis and review).

These pre- and peri menopause conditions that results in lower progesterone is a phenomenon well known as estrogen dominance, and lower BMD is only one of many health risks it causes. The logical thing to do in these conditions is to boost progesterone by low dose transdermal progesterone made of real progesterone (That's what has been recommended by Ray Peat and John R. Lee as a preventative treatment for estrogen dominance) as opposed to progesterone mimicking drugs used in birth control drugs and hormone therapy drugs.

Also, let's not forget that stress (high cortisol) reduces progesterone secretion for a prolonged period (Stress and female reproductive function: a study of daily variations in cortisol, gonadotrophins, and gonadal steroids in a rural Mayan population. Pablo A Nepomnaschy, Kathy Welch, Dan McConnell, Beverly I Strassmann, Barry G England 2004; Stress and the menstrual cycle: relevance of cycle quality in the short- and long-term response to a 5-day endotoxin challenge during the follicular phase in the rhesus monkey. E Xiao, L Xia-Zhang, A Barth, J Zhu, M Ferin 1998; Inadequate luteal function is the initial clinical cyclic defect in a 12-day stress model that includes a psychogenic component in the Rhesus monkey. Ennian Xiao, Linna Xia-Zhang, Michel Ferin. 2002), thus amplify the harmful effects of cortisol in pre- and peri-menopause years (So imagine how disadvantaged your body is in post menopause years without real progesterone supplementation).

As I said, the logical thing to do in these situations is to boost progesterone, however, I have yet to come across a study that is designed to examine the effects of progesterone supplementation during pre- and peri-menopause years. If you are a researcher in this field, here is a chance to make a name for yourself. Just make sure that progesterone is transdermal, real, potent, and does not exceed 40mg/day.

 

Bone series articles:

1. Menopause and What Really Happens to your Bones
2. False Promise of Fosamax
3. Estrogen Paradox
4. Role of Progesterone in Bone Health  <<You are here
   
5. Stress Hormones Destroy Bones
6. Menopause and How estrogen helps bone health?
7. Sad State of Progesterone Research
8. Bone Quality Is Just as Important as Density
9. How to Maintain Bone Health