Bahamas Anti-Aging Medical Institute

Women’s health is an enormous topic — and it’s one that has only come into its own in the past 30 years. Before that time most people (including physicians, unfortunately) saw women’s health issues as being essentially related to obstetrics and gynecology — the areas in which women’s bodies differ most obviously from men’s. But we’ve made great strides since then, both as a society and as a community of health professionals.

We now understand that the sex hormones, estrogen, progesterone, testosterone, and their derivatives, are found in some quantity in people of both sexes — and we know that these vital cellular signaling molecules have functions that extend far beyond simply running our reproductive systems. In fact, all of the major sex hormones are now recognized to be neurosteroid hormones with powerful effects on brain structures that begin even before birth ^1-5.

We now recognize that age-related changes in sex hormone levels are intimately and intricately involved in many of the other age-related changes that our bodies experience – so it’s no accident that women age differently than do men. Fierce debates continue to rage about how and whether hormone replacement therapy is safe and effective at preventing or reversing some of these changes ^6-8. The answers are likely to be as complicated as the endocrine (hormonal) system itself, so stay tuned to this website and others like it to keep abreast of emerging data. Here are just a few of the ways in which we now recognize a vital role for sex hormones in women’s health:

• Everyone complains about menopause, but no one does anything about it, to paraphrase Mark Twain. Of course, medical scientists have been exploring the phenomenon known as menopause for decades, and some progress has been made. Menopause occurs when levels of the primary female sex hormone, estrogen, fairly suddenly drop. The familiar hot flashes, mood changes, and other symptoms are all essentially related to estrogen withdrawal. There’s also evidence that significant brain functions are affected, possibly related to ultimate cognitive decline ^9-11.
• Osteoporosis [Link to Osteoporosis Article] is a potentially-devastating consequence of dropping estrogen levels; while not unique to women, it is still much more common than in men. Recent studies have raised major safety issues about hormone replacement therapy, relating it to increased cancer and cardiovascular disease ⁸. Fortunately, many nutritional interventions are available, and regular exercise can also stave off the progress of this crippling condition. Bisphosphonate drugs (like Fosamax® and others) may play a role when used properly.
• Cardiovascular disease — it’s not just for men anymore. Women have probably had higher rates of heart attacks than we recognized for years (in fact they have them almost as often as men), but because heart attack symptoms are different in women we often missed the signs until it was too late ¹². Couple that with a genuine increase in obesity, type 2 diabetes, atherosclerosis, and other plagues of modern society, and we have a genuine epidemic on our hands ¹³. Recent evidence shows that estrogen has direct effect on maintaining the health of heart muscle, which may explain why women tend to develop cardiovascular disease at older ages than do men ^14,15. Dropping estrogen levels may be related to the blood vessel changes called atherosclerosis, and many of the very factors that cause bone to lose calcium in osteoporosis actually cause calcium deposits to grow in blood vessel walls, contributing to inflammation and vessel blockage ^16-18. These factors all contribute to increased risk of heart attacks, strokes, and other diseases of the cardiovascular system, especially at and after menopause ^19-22.
• Cancer is a threat to everyone with advancing age, but cancers of the ovary and uterus, and most breast cancers, are of course unique to women²³. We’re learning, sadly, that other cancer rates are rapidly rising in women — lung cancer rates in particular have skyrocketed in the past 40 years^24,25. Most scientists who understand the causation of cancer believe that these increases are related in part to our sedentary lifestyles and in part to dietary and environmental factors that trigger cancers and then stimulate their further growth through a combination of oxidative stress and inflammation; fortunately, we’re also learning how dietary and lifestyle interventions can address many of these factors^26,27.
• Cognitive decline – just as the female brain forms differently during fetal development as the result of estrogen, it also ages differently in full maturity as the result of a lifetime of estrogen exposure and the abrupt withdrawal of estrogen at menopause ^2,4,5. Scientists are just now beginning to understand how diet, lifestyle, and nutritional supplements can help to prevent and, in some cases, actually reverse some of these changes.

For more in-depth coverage of women’s health issues, go to the Life Extension

Foundation’s on-line textbook at http://www.lef.org/protocols/.

References

(1) Tsutsui K. Progesterone biosynthesis and action in the developing neuron. Endocrinology. 2008;149:2757-2761.

(2) Wang JM, Irwin RW, Liu L, Chen S, Brinton RD. Regeneration in a degenerating brain: potential of allopregnanolone as a neuroregenerative agent. Curr Alzheimer Res. 2007;4:510-517.

(3) Mellon SH. Neurosteroid regulation of central nervous system development. Pharmacol Ther. 2007;116:107-124.

(4) Bicikova M, Hampl R. [Neurosteroids and their function]. Cas Lek Cesk. 2007;146:223-226.

(5) Leskiewicz M, Budziszewska B, Basta-Kaim A, Zajac A, Kacinski M, Lason W. Effects of neurosteroids on neuronal survival: molecular basis and clinical perspectives. Acta Neurobiol Exp (Wars ). 2006;66:359-367.

(6) Pike MC, Wu AH, Spicer DV, Lee S, Pearce CL. Estrogens, progestins, and risk of breast cancer. Ernst Schering Found Symp Proc. 2007;127-150.

(7) Prentice RL. Women's health initiative studies of postmenopausal breast cancer. Adv Exp Med Biol. 2008;617:151-60.:151-160.

(8) Billeci AM, Paciaroni M, Caso V, Agnelli G. Hormone replacement therapy and stroke. Curr Vasc Pharmacol. 2008;6:112-123.

(9) Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006;3:185-190.

(10) Legrain S, Girard L. Pharmacology and therapeutic effects of dehydroepiandrosterone in older subjects. Drugs Aging. 2003;20:949-967. Copyright 2008 – Bahamas Anti Aging Medical Institute – page 4 of 6

(11) Vallee M, Mayo W, Darnaudery M et al. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci U S A. 1997;94:14865-14870.

(12) Regitz-Zagrosek V, Lehmkuhl E, Lehmkuhl HB, Hetzer R. Gender aspects in heart failure. Pathophysiology and medical therapy. Arch Mal Coeur Vaiss. 2004;97:899-908.

(13) Vitale C, Miceli M, Rosano GM. Gender-specific characteristics of atherosclerosis in menopausal women: risk factors, clinical course and strategies for prevention. Climacteric. 2007;10 Suppl 2:16-20.:16-20.

(14) Regitz-Zagrosek V. Cardiovascular disease in postmenopausal women. Climacteric. 2003;6 Suppl 3:13-20.:13-20.

(15) Nordmeyer J, Eder S, Mahmoodzadeh S et al. Upregulation of myocardial estrogen receptors in human aortic stenosis. Circulation. 2004;110:3270-3275.

(16) Beulens JW, Bots ML, Atsma F et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2008.

(17) Saito E, Wachi H, Sato F, Sugitani H, Seyama Y. Treatment with vitamin k(2) combined with bisphosphonates synergistically inhibits calcification in cultured smooth muscle cells. J Atheroscler Thromb. 2007;14:317-324. Copyright 2008 – Bahamas Anti Aging Medical Institute – page 5 of 6

(18) Kaneki M, Hosoi T, Ouchi Y, Orimo H. Pleiotropic actions of vitamin K: protector of bone health and beyond? Nutrition. 2006;22:845-852.

(19) Carlson S, Peng N, Prasain JK, Wyss JM. Effects of botanical dietary supplements on cardiovascular, cognitive, and metabolic function in males and females. Gend Med. 2008;5 Suppl A:S76-90.:S76-S90.

(20) Meyer MR, Haas E, Barton M. Need for research on estrogen receptor function: importance for postmenopausal hormone therapy and atherosclerosis. Gend Med. 2008;5 Suppl A:S19-33.:S19-S33.

(21) Collins P, Rosano G, Casey C et al. Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists. Climacteric. 2007;10:508-526.

(22) Thomas CM, Smart EJ. Gender as a regulator of atherosclerosis in murine models. Curr Drug Targets. 2007;8:1172-1180.

(23) Prat J, Gallardo A, Cuatrecasas M, Catasus L. Endometrial carcinoma: pathology and genetics. Pathology. 2007;39:72-87.

(24) Mazieres J, Rouquette I, Brouchet L. [Lung cancer in women and pregnancy: towards a hormonal origin?]. Rev Mal Respir. 2007;24:983-997. Copyright 2008 – Bahamas Anti Aging Medical Institute – page 6 of 6

(25) Ben-Zaken CS, Pare PD, Man SF, Sin DD. The growing burden of chronic obstructive pulmonary disease and lung cancer in women: examining sex differences in cigarette smoke metabolism. Am J Respir Crit Care Med. 2007;176:113-120.

(26) Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007;55:224-236.

(27) Gazak R, Walterova D, Kren V. Silybin and silymarin--new and emerging applications in medicine. Curr Med Chem. 2007;14:315-338.