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Life Extension Magazine

LE Magazine June 2003

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The Overlooked Female Hormone

By Melissa L. Block, M.Ed.

If ovulation does not occur, no progesterone is made. Ano­vulatory cycles are not easily detected, since menstruation still happens on schedule as long as estrogen does its part. The resulting imbalance of estrogen (which reaches its highest levels at around the 12th day of the menstrual cycle, with the first day falling on the first day of menstruation) and progesterone leads to a condition of estrogen dominance. When this cycle repeats itself frequently, and when it is amplified by environmental estrogens and those made in excess body fat, the body is in a near-constant state of estrogen overload. Estrogen-sensitive tissues get the message to grow and proliferate, and the symptoms listed in the sidebar on page 73 are the end result. By adding progesterone back into each cycle, and gently augmenting progesterone production during ovulatory cycles, balance can be reestablished.

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Women who are in or past menopause can also benefit from natural progesterone supplementation. Natural progesterone stimulates the formation of new bone and may help to prevent breast cancer. It counteracts the blood clotting effects of estrogens, improves vascular tone (the ability of blood vessels to stretch and contract in response to the body's requirements), and is believed to protect against the buildup of atherosclerotic plaques and coronary artery spasms that lead to heart attack.5-7 It's a gentle mood enhancer and helps to maintain normal libido.

Low thyroid activity is a common problem for postmenopausal women. Estrogen inhibits thyroid hormone activity.19 Balancing excess estrogens with progesterone enables the body to better utilize thyroid hormone, and can help women to wean themselves off of thyroid hormone replacement drugs.

Progesterone builds bones

One of the main arguments in favor of HRT is that it has been shown in multiple studies to preserve bone mass and protect against osteoporotic fractures. The truth is that while estrogens - even the horse-derived estrogens that comprise Premarin - do preserve bone mass, the overall risks of HRT have been found to outweigh any beneficial effects it might have on bone health.

The synthetic progestin medroxyprogesterone has been found to increase bone density when given to young women who are not menstruating or ovulating.20 The work of John Lee, M.D., and other like-minded clinicians has shown that natural progesterone has the same bone-building effect in both pre- and postmenopausal women, without the side effects that often occur with the synthetic progestins.

Estrogen maintains bone mass by subduing the activity of osteoclasts - specialized bone cells that break down old bone to make room for new. Progesterone builds bone by stimulating the activity of osteoblasts, bone cells that pull calcium, magnesium and phosphorus from the blood so that it can be incorporated into the bones.

Progesterone and breast cancer

Progesterone modulates much more than the course of a pregnancy. It interacts with estrogen in dozens of ways; the best detailed explanation of these effects can be found in Dr. Lee's writings. The short story on progesterone's relationship with cancer is that while estrogen encourages cellular growth (which is why it is carcinogenic in excess), progesterone encourages cells to differentiate, or mature. Immature cells are more likely to turn into cancerous cells.

Progesterone also encourages cells to undergo apoptosis - programmed cell death. A cell that becomes cancerous avoids apoptosis; it can continue to divide and survive as long as it has fuel and a place to grow. The mechanisms by which estrogen encourages cell growth are also thought to help switch off the genetic machinery that brings on programmed cell death.9-12

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Progesterone also reduces the production of a carcinogenic form of estrogen (4-hydroxyestrone) and enhances the production of estriol, a safer, non-carcinogenic estrogen. Breast cancer surgery or biopsy performed during the luteal phase of the menstrual cycle - the phase during which progesterone levels peak - is associated with significant improvements in prognosis and survival time.21-23 Proges­terone counteracts estrogen's effects on breast duct cells, which are usually the place where breast tumors begin to form.

Estrogen encourages breast duct cell proliferation; progesterone encourages those cells to mature and differentiate. This is how estrogen and progesterone interact during pregnancy to ready the breasts for lactation. Mature, differentiated cells are far less vulnerable to cancerous changes, a fact that explains why women who have had full-term pregnancies are at less risk of developing breast cancer.

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How to Supplement with natural progesterone

When taken orally, natural progesterone is almost completely degraded by the liver before it can reach the tissues that need it. Even micronized natural progesterone - now available as a prescription drug called Prometrium® - must be given in high doses to make it through the first pass through the liver. This puts undue stress on the liver and may create metabolites that have harmful effects.

Natural progesterone can be given in the form of suppositories and injections. Both work to move progesterone into the bloodstream, but the first is messy and the latter is inconvenient. The simplest way to supplement with progesterone is transdermally, in the form of a skin cream that contains bioidentical progesterone made from soy or wild yams. When the cream is smoothed onto the skin, the progesterone molecules are absorbed into the layer of subcutaneous fat. The bioavailability of transdermal progesterone has been proven in several studies.

Once absorbed through the skin, the progesterone molecules gradually diffuse into the circulation. This method provides the closest possible approximation to the natural production of progesterone by the ovaries - as long as the dosages are properly timed.

Massage progesterone cream into the breasts, chest, underarms, face, abdomen, buttocks or inner thighs. Rotate the site where cream is applied so that subcutaneous fat cells don't become saturated in any one site. Use a cream that contains 500 mg to 700 mg of progesterone per ounce.

Premenopausal women: Women who have not gone through menopause and have estrogen dominance symptoms (including fibrocystic breasts and ovarian cysts) should use 1/4 to 1/2 tsp of progesterone cream, an amount which should provide 20 mg to 40 mg of progesterone, starting on the 8th day of the cycle. (Day one is the first day of menstruation.)

Continue to apply the cream until day 26 of the cycle, and allow seven days (whether menstruation occurs or not) before begin­ning to apply it again.

PMS: Begin to apply 1/4 tsp of cream on the 12th day after the first day of menstruation and continue until day 26.

Endometriosis: Women with endometriosis should use 1/2 tsp twice a day from days 6 through 26 of the menstrual cycle.

Menopausal and postmenopausal women: Women who are past menopause or who have had a hysterectomy should use 1/4 to 1/2 tsp of cream twice a day for 25 days, followed by five days off. Repeat this cycle for three months, then decrease the dosage to 1/4 tsp twice a day. If you have a uterus and are using supplemental estrogen of any kind, use progesterone cream every day of the month.

Osteoporosis: To help prevent osteoporosis in postmenopausal women, use 1/8 to 1/4 tsp daily from the 12th day to the last day of each monthly cycle. If still menstruating, use the first day of your period to mark the first day of the cycle. Women who have been diagnosed with osteoporosis should apply 1/2 teaspoon morning and night until the first jar is used up, and then 1/4 teaspoon morning and night until the second jar is used up. The latter dosage can be used for maintenance, or can be cut in half once again if bone scans show improvement. In addition to progesterone, supplementation with at least 1000 mg a day of calcium along with magnesium, zinc, boron, manganese, vitamin D and vitamin K are essential in the prevention of osteoporosis.

Progesterone supplementation

Natural progesterone cream is increasingly being used in lieu of synthetic progestin drugs. Like any hormone - natural or synthetic - it's bound to have more significant effects in some people than in others, because of subtle biochemical differences. Fortunately, there is no risk involved in trying it as long as it is used properly. Natural progesterone is now available in an enhanced delivery skin cream (QuSome® encapsulated) to better maintain a consistent youthful level of progesterone in the body.


References

1. Prior JC. Perimenopause: the complex endocrinology of the menopausal transition. Endocr Rev 1998 Aug;19(4):397-428.

2. Teede HJ, et al. A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function. Clin Endocrinol (Oxf) 2001 Nov;55(5):673-82.

3. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy menopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333.

4. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999 Aug;94(2):225-8.

5. Mercuro G, et al. Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women. Am J Cardiol 1999 Jul 15;84(2):214-8.

6. Ylang YL, et al. Effects of estrogen and progesterone on age-related changes in arteries of postmenopausal women. Clin Exp Pharmacol Physiol 1997 Jun;24(6):457-9.

7. Hata K, et al. Transition of ovarian arterial compliance during the human menstrual cycle, assessed by Doppler ultrasound-correlation with serum hormone levels. Nippon Sanka Fujinka Gakkai Zasshi 1990 Jul;42(7):662-6.

8. Prior JC. Progesterone as a bone-trophic hormone. Endocr Rev 1990 May;11(2):386-98.

9. Chang KJ, et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 1995 Apr;63(4):785-91.

10. Foidart JM, et al. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril 1998 May;69(5):963-9.

11. Horita K, et al. Progesterone induces apoptosis in malignant mesothelioma cells. Anticancer Res 2001 Nov-Dec;21(6A):3871-4.

12. Formby B, Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Ann Clin Lab Sci 1998 Nov-Dec;28(6):360-9.

13. Desreux J, et al. Progesterone receptor activation. An alternative to SERMs in breast cancer. Eur J Cancer 2000 Sep;36 Suppl 4:S90-1.

14. Zapantis G, Santoro N. Ovarian ageing and the menopausal transition. Best Pract Res Clin Obstet Gynaecol 2002 Jun;16(3):263-76.

15. te Velde ER, et al. Developmental and endocrine aspects of normal ovarian aging. Mol Cell Endocrinol 1998 Oct 25;145(1-2):67-73.

16. Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Fertil Steril 2003 Jan;79(1):221-2.

17. Cooper A, et al. Systemic absorption of progesterone from Progest cream in postmenopausal women. Lancet 1998 Apr 25;351(9111):1255-6.

18. Annual meeting of the society for maternal-fetal medicine, February 6, 2003.

19. Vasudevan N, Ogawa S, Pfaff D. Estrogen and thyroid hormone receptor interactions: physiological flexibility by molecular specificity. Physiol Rev 2002 Oct;82(4):923-44.

20. Prior JC, et al. Perimenopausal bone loss: more than estrogen depletion. J Bone Miner Res 2001 Dec;16 (12):2365-6. 25.

21. Cooper LS, et al. Survival of premenopausal breast carcinoma patients in relation to menstrual cycle timing of surgery and estrogen receptor/progesterone receptor status of the primary tumor. Cancer 1999 Nov 15;86(10):2053-8.

22. Badwe RA, Mittra I, Havaldar R. Timing of surgery during the menstrual cycle and prognosis of breast cancer. J Biosci 2000 Mar;25(1):113-20.

23. Macleod J, Fraser R, Horeczko N. Menses and breast cancer: does timing of mammographically directed core biopsy affect outcome? J Surg Oncol 2000 Jul;74(3):232-6.

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