How old do people think you are? Are you 60 going on 25? Then you are well on your way to a life of longevity. Perceived age is a term often used by physicians to recognize a patient’s level of health, in which an individual may look younger or older than his or her chronological age. Is there really an internal fountain of youth that radiates through your appearance?

Researchers from the University of Denmark decided to put this idea to the test. The study recruited 1,826 Danish twins (70 years and older) to take physical and cognitive tests. The twins also had their faces photographed. Next, volunteers looked at the photos and determined the subjects’ age based on their appearance. After a seven-year follow up, researchers found that longevity was significantly related to perceived age, as it was more likely that the older-looking twin died first. Additionally, younger-looking individuals had greater physical and mental capacities.

Researchers concluded common genetic factors associated with a younger appearance might also explain the findings. They determined perceived age is a strong indication of aging and longevity.

Reference

Christensen K, Thinggaard M, McGue M, Rexbye H, et al. Perceived age as clinically useful biomarker of ageing: cohort study. BMJ. 2009 Dec 10;339:b5262.

Description

The butterfly-shaped thyroid gland is located in the front of your neck and wraps partially around the windpipe. The gland is responsible for making thyroid hormones that control the metabolism of all cells in your body.

If the thyroid overproduces hormones, you can have a condition called hyperthyroidism. This condition commonly causes symptoms such as a forceful and rapid heart beat, insomnia, sudden weight loss, breathlessness, nervousness, irritability, sweating, and frequent bowel movements.1

Many people can also suffer from different degrees of low or underactive thyroid function, called hypothyroidism. Symptoms of a thyroid gland producing too little thyroid hormone can include a slow metabolism, listlessness, lowered body temperature, weight gain, constipation, muscle soreness, feeling cold, fatigue, depression, high cholesterol and homocysteine, painful joints, dry skin, and hair loss.1-4

There are two types of thyroid hormones: Thyroxine (T4) and Triiodothyronine (T3). T4 is inactive and kept in reserve; T3 is the active hormone. Thyroid hormones control the growth, differentiation, and metabolism of each cell in our body. They also control how fast our body uses the fuel that we consume, particularly carbohydrates and fat.1 This helps to regulate our body temperature and fat percentage. About 80% of thyroid hormone production is T4, the inactive thyroid hormone that is typically held in reserve by the body. T3 makes up only 20% of thyroid hormone production,5 but it is the active hormone that the body uses to function. T4 is converted into T3 when thyroid hormone is needed.

The release of the thyroid hormones is controlled by the thyroid stimulating hormone (TSH), which is produced in the pituitary gland. Low circulating levels of thyroid hormone are detected by the hypothalamus, which then instructs the pituitary to release TSH. When sufficient amounts are released, the hypothalamus communicates with the pituitary to stop or slow down. Because of this complicated feedback loop, high levels of TSH in the blood often mean the pituitary is trying to stimulate thyroid hormone production, but the thyroid gland is not responding. This condition is known as hypothyroidism.

 Benefits of Thyroid

• Regulates temperature, metabolism, and cerebral function
• Increases energy, body temperature, and warmth
• Increases fat breakdown, resulting in decreased weight and lower cholesterol2
• Protects against cardiovascular ailments3,6
• Improves cerebral metabolism
• Supports cognitive function7
• Relieves symptoms of thin sparse hair, dry skin, and brittle nails

Side Effects

The most common side effects from too high a dose of thyroid hormone are heart palpitations,8 increased pulse, excessive sweating, heat intolerance, and nervousness.

Administration

The recommended form of thyroid replacement is an Armour Thyroid Compound, which is a combination of T3 and T4.9 Studies show that a percentage of patients prefer the combination of T4 and T3 over T4 alone.10,11 The combination allows the body to receive the active and inactive form to treat those patients who are not able to properly convert. In contrast, traditional physicians continue to prescribe the synthetic thyroid hormone T4 or Synthroid. Synthroid is only T4 and may not convert to T3.

References

1. Huber MA, Terézhalmy GT. Risk stratification and dental management of the patient with thyroid dysfunction. Quintessence Int. 2008 Feb;39(2):139-50.
2. Asranna A, et al. Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S347-9.
3. Kutluturk F, et al. Changes in metabolic and cardiovascular risk factors before and after treatment in overt hypothyroidism. Med Glas (Zenica). 2013 Aug;10(2):348-53.
4. Rao ML, et al. Low plasma thyroid indices of depressed patients are attenuated by antidepressant drugs and influence treatment outcome. Pharmacopsychiatry. 1996 Sep;29(5):180-6.
5. Sapin R, Schlienger JL. [Thyroxine (T4) and tri-iodothyronine (T3)determinations: techniques and value in the assessment of thyroid function]. Ann Biol Clin (Paris). 2003 Jul-Aug;61(4):411-20.
6. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med.2001;344(7): 501-509.
7. Bunevicius R, et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med. 1999 Feb 11;340(6):424-9.
8. Toft AD. Thyroid hormone replacement – one or two? N Engl J Med. 1999 Feb 11;340(6):469-70.
9. Gaby AR. Sub-laboratory hypothyroidism and the empirical use of Armour thyroid. Altern Med Rev. 2004 Jun; 9(2):157-179.
10. Escobar-Morreale HF, et al. Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 Mar 15;142(6):412-24.
11. Sesmilo G, et al. Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism.Endocrinol Nutr. 2011 Jan;58(1):9-15.

Description

Testosterone, important to both men and women,1 is a hormone secreted by the ovaries, adrenal glands, and testes.2 Women require less testosterone than men, but the hormone is needed to sustain a woman’s libido and enhance the functions of estrogen.3 In both males and females, it strengthens bones to help prevent bone loss.2

Testosterone is the primary male sex hormone, responsible for male sexual development and critical in maintaining erectile function, libido, energy levels, mood, and a wide range of other physical functions throughout the body.2 As with other hormones, testosterone declines with age. Testosterone levels begin declining when a man is in his thirties. Although the total testosterone does not drop dramatically, the free testosterone, which is the biologically active testosterone, declines dramatically with age.4 Because the drop in testosterone is gradual, andropause symptoms appear over a longer period of time as compared to female menopause.5 Symptoms appear as a gradual decrease in energy, thinning bones and muscles, increased visceral fat, depression, and impaired sexual function.1,5,6 Testosterone deficiency has also been linked to hypertension, obesity, and increased heart disease risks. Stress levels may also play a role in declining testosterone levels. Testosterone replacement therapy is available @ Preventative Medicine Clinic in Bend.

Benefits of Testosterone Therapy or Testosterone Optimization

The focus of testosterone therapy and reaching optimal levels result in:

• Increase in bone density, bone formation, and bone minerals2,7-10
• Increase in energy5,11-13
• Improvement in sexual function3,5,6,11,13-19
• Increase in sexual satisfaction16,18-20
• Decrease in body fat or improved body composition5,7-9,12,16,18,21
• Balance healthy cholesterol and/or improve lipid profiles21,22
• Decrease in cardiovascular ailments5,7,16,21,23-25
• Improved brain function, learning, concentration, and memory5,12,16,26
• Improved blood glucose levels5,7,21
• Balance healthy blood pressure5,21,22
• Increase in sexual desire16,20,22,27-29
• Increase in both muscle strength and in the diameter of muscle fibers8,30
• Enhancement of skin and hair texture5
• Improved mood6,10,11,13,14,18,22,29,31,32

Side Effects

Too much testosterone can increase aggressive behavior. Testosterone should not be prescribed if prostate cancer is present. Testosterone has not been shown to cause prostate cancer; however, it may accelerate the growth of a tumor. PSA levels should be monitored yearly or every 6 months.

Administration

Testosterone therapy includes administration of bio-identical or synthetic testosterone orally, by injection (hormone pellets), patches, pellet implants or application of a cream/gel form. The most common way to take testosterone is in the cream or gel form. It is quickly absorbed, short-acting, and less toxic for the liver. Dosing is usually done in the morning and evening, and the strength varies from 50–100 mg. Other testosterone therapy includes implantation of pellets and regular injections. Many patients find these delivery systems convenient and cost effective.

Frequently Asked Questions

Q. Will women taking testosterone have an increase in hair growth?
A. No. They would have to take a man’s dose to experience any hair growth. While men take 100–200 mg daily, women take only 4–8 mg.

Q. How often can I get my prescription refilled?
A. Testosterone is a controlled substance and cannot under any circumstances be refilled before your dose is due to run out. Take your medication exactly as prescribed by your doctor.

Q. Will taking testosterone cause my body’s own production to decrease?
A. Yes, it can in some cases and some men may experience a small decrease in testicle size, which may be unsettling but does not impact sexuality or well-being.

References

1. Horstman AM, et al. The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1140-52.

2. De Oliveira DH, et al. Androgens and bone. Minerva Endocrinol. 2012 Dec;37(4):305-14.

3. van Anders SM, et al. Preliminary clinical experience with androgen administration for pre- and postmenopausal women with hypoactive sexual desire. J Sex Marital Ther. 2005
May-Jun;31(3):173-85.

4. Krasnoff JB, et al. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab. 2010 Jun;95(6):2790-9.

5. Tsujimura A. The Relationship between Testosterone Deficiency and Men’s Health. World J Mens Health. 2013 Aug;31(2):126-135.

6. Hori Y, et al. Clinical study of 62 patients with symptoms of male climacterium. Hinyokika Kiyo. 2013 Aug;59(8):491-5.

7. Corona G, et al. Risks and Benefits of Late Onset Hypogonadism Treatment: An Expert Opinion. World J Mens Health. 2013 Aug;31(2):103-125.

8. Cunningham GR. Andropause or Male Menopause? Rationale for Testosterone Replacement Therapy in Older Men with Low Testosterone Levels. Endocr Pract. 2013 Sep 6:1-18. PubMed PMID: 24014001.

9. Miller KK, et al. Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2011 Jul;96(7):2081-8.

10. Dolan Looby SE, et al. Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial. AIDS. 2009 May 15;23(8):951-9.

11. Amano T. Role of Androgen in the Elderly. Clinical androgen replacement therapy for late-onset hypogonadism. Clin Calcium. 2013 Aug;23(8):1179-84.

12. Blick G. Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels. Postgrad Med. 2013 Mar;125(2):30-9.

13. Studd J. Ten reasons to be happy about hormone replacement therapy: a guide for patients. Menopause Int. 2010 Mar;16(1):44-6.

14. Miner MM, et al. Twelve-month observation of testosterone replacement effectiveness in a general population of men. Postgrad Med. 2013 Mar;125(2):8-18.

15. Panay N, et al. Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric. 2010 Apr;13(2):121-31.

16. Davis SR. Androgen therapy in women, beyond libido. Climacteric. 2013 Aug;16 Suppl 1:18-24.

17. Abdallah RT, Simon JA. Testosterone therapy in women: its role in the management of hypoactive sexual desire disorder. Int J Impot Res. 2007 Sep-Oct;19(5):458-63.

18. Blick G, et al. Testosterone replacement therapy in men with hypogonadism and HIV/AIDS: results from the TRiUS registry. Postgrad Med. 2013 Mar;125(2):19-29.

19. Kingsberg S, et al. Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. J Sex Med. 2007 Jul;4(4 Pt 1):1001-8.

20. Davis S, et al. Safety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal women: a randomized trial. Ann Intern Med. 2008 Apr 15;148(8):569-77.

21. Saad F. Androgen therapy in men with testosterone deficiency: Can testosterone reduce the risk of cardiovascular disease? Diabetes Metab Res Rev. 2012 Dec;28 Suppl 2:52-9.

22. Stephenson K, Neuenschwander PF, Kurdowska AK. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. Int J Pharm Compd. 2013 Jan-Feb;17(1):74-85.

23. Poliwczak AR, Tylińska M, Broncel M. Effect of short-term testosterone replacement therapy on heart rate variability in men with hypoandrogen-metabolic syndrome. Pol Arch Med Wewn. 2013 Aug 19. doi:pii: AOP_13_047. PubMed PMID: 23974276.

24. He H, et al. Sex hormone ratio changes in men and postmenopausal women with coronary artery disease. Menopause. 2007 May-Jun;14(3 Pt 1):385-90.

25. Worboys S, et al. Evidence that parenteral testosterone therapy may improve endothelium-dependent and -independent vasodilation in postmenopausal women already receiving estrogen. J Clin Endocrinol Metab. 2001 Jan;86(1):158-61.

26. Möller MC, et al. Effect of estrogen and testosterone replacement therapy on cognitive fatigue. Gynecol Endocrinol. 2013 Feb;29(2):173-6.

27. Gettler LT, et al. Do testosterone declines during the transition to marriage and fatherhood relate to men’s sexual behavior? Evidence from the Philippines. Horm Behav. 2013 Sep 7.PubMed PMID: 24018138.

28. Lejeune H, Huyghe É, Droupy S. Hypoactive sexual desire and testosterone deficiency in men. Prog Urol. 2013 Jul;23(9):621-8.

29. Vigesaa KA Pharmd, et al. Efficacy and Tolerability of Compounded Bioidentical Hormone Replacement Therapy. Int J Pharm Compd. 2004 July-Aug;8(4):313-319.

30. Sinha-Hikim I, et al. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E197-205.

31. Miller KK, et al. Low-dose transdermal testosterone augmentation therapy improves depression severity in women. CNS Spectr. 2009 Dec;14(12):688-94.

32. Goldstat R, et al. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause. 2003 Sep-Oct;10(5):390-8.

Description

Progesterone is a hormone produced by the ovaries and adrenal glands, and it functions to balance the effects of estrogen. Natural progesterone enhances the action of estrogen, as these hormones work together to maintain a normal hormone balance. A lack of progesterone causes disease processes similar to those caused by a deficiency of estrogen. They include osteoporosis, heart disease, decrease in libido, and a significantly diminished quality of life. The combination of natural progesterone and estrogen can prevent this downward spiral by keeping women vital, strong, and healthy.

The ovaries begin producing progesterone around puberty, and the monthly ebb and flow of this hormone, in harmony with estrogen and other hormones, continues until menopause. Progesterone’s primary role during this moment is to help make the uterus ready for implantation of a new embryo, the first major event – after fertilization of the egg – in the nine months of human gestation. If the egg is not fertilized, progesterone production temporarily ceases, and the uterus sheds its endometrial lining.

Benefits of Progesterone Replacement

• Precursor to the sex hormones (estrogen and testosterone)1
• Maintains uterine lining2
• Promotes the survival of the embryo and fetus throughout gestation3-5
• Supports hormonal balance supporting breast tissue against fibrocystic breasts6
• Natural diuretic7
• Supports healthy moods by itself and when balanced with other hormones8-14
• Aids thyroid hormone action15-18
• Supports healthy blood clotting19-21
• Supports a healthy brain and neuroplasticity22-28
• Helps healthy blood sugar levels29-34
• Protects against abnormal cell development in the endometrium and breast tissue35-40
• Sustains strong bones41-43

Side Effects

There are no side effects associated with natural progesterone. However, women who are estrogen-dominant may experience premenstrual mood swings, depression, breast swelling, heavy or irregular periods, and sleep disturbances. If a dose of progesterone is missed, a woman may experience menstrual bleeding.

Administration

Natural progesterone comes in many forms, most commonly a topical cream, an oral capsule, and a sublingual tablet. Progesterone’s half-life is approximately eight hours, which results in the need to take natural progesterone twice a day. Progesterone levels should be measured by a physician to ensure levels are in a therapeutic range.

References

1. Imataka H, et al. Biosynthetic pathways of testosterone and estradiol-17 beta in slices of the embryonic ovary and testis of the chicken (Gallus domesticus). Gen Comp Endocrinol. 1989 Jan;73(1):69-79.
2. Csapo AI, Pinto-Dantas CA. The effect of progesterone on the human uterus.
   Proc Natl Acad Sci U S A. 1965 October; 54(4): 1069–1076.
3. Halasz M, Szekeres-Bartho J. The role of progesterone in implantation and
   trophoblast invasion. J Reprod Immunol. 2013 Mar;97(1):43-50.
4. Spencer TE, Bazer FW. Biology of progesterone action during pregnancy
   recognition and maintenance of pregnancy. Front Biosci. 2002 Sep 1;7:d1879-98.
5. Kumar P, Magon N. Hormones in pregnancy. Niger Med J. 2012 Oct;53(4):179-83.
6. Thalabard JC, et al. Endocrine markers in benign breast diseases]. Zentralbl Gynakol. 1986;108(6):354-8.
7. Couette B, et al. Aldosterone antagonists destabilize the mineralocorticosteroid receptor.Biochem J. 1992 Mar 15;282 ( Pt 3):697-702.
8. Kulkarni J, et al. A pilot study of hormone modulation as a new treatment
   for mania in women with bipolar affective disorder. Psychoneuroendocrinology.
   2006 May;31(4):543-7.
9. Chouinard G, et al. Estrogen-progesterone combination: another mood stabilizer? Am JPsychiatry. 1987 Jun;144(6):826.
10. Huang MC, et al. Estrogen-progesterone combination for treatment-refractory post-partum mania. Psychiatry Clin Neurosci. 2008 Feb;62(1):126.
11. Frye CA. Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice. Pharmacol Biochem Behav. 2011 Oct;99(4):525-31.
12. Carta MG, et al. GABAergic neuroactive steroids: a new frontier in bipolar disorders?Behav Brain Funct. 2012 Dec 19;8:61. doi
13. Valenzuela SK. The power of natural progesterone: treating hormone-related
    postpartum depression. Midwifery Today Int Midwife. 2012 Autumn;(103):22-5.
14. Schwartz E, Holtorf K. Hormone replacement therapy in the geriatric patient:
    current state of the evidence and questions for the future. Estrogen,
    progesterone, testosterone, and thyroid hormone augmentation in geriatric
    clinical practice: part 1. Clin Geriatr Med. 2011 Nov;27(4):541-59.
15. Kumar P, Magon N. Hormones in pregnancy. Niger Med J. 2012 Oct;53(4):179-83.
16. Jahagirdar V, et al. Maternal hypothyroidism decreases progesterone receptor expression in the cortical subplate of foetal rat brain. J Neuroendocrinol. 2012 Aug;24(8):1126-34.
17. Szelényi Z, Péczely P. Thyroxin induced moult in domestic hen. Acta Physiol Hung. 1988;72(2):143-9.
18. Leers J, et al. A thyroid hormone receptor-dependent glucocorticoid induction. MolEndocrinol. 1994 Apr;8(4):440-7.
19. Kaibara M, et al. Effect of high-dose progestogen on hemostatic properties of blood in patients with endometrial cancer. Clin Hemorheol Microcirc. 2001;24(2):93-9.
20. Matsuoka T, et al. Effects of restricted feeding on fetal and placental development in pregnant rabbits. J Toxicol Sci. 2012 Feb;37(1):207-14.
21. Henriquez S, et al. Progesterone utilizes distinct membrane pools of tissue factor to increase coagulation and invasion and these effects are inhibited by TFPI. J Cell Physiol. 2011 Dec;226(12):3278-85.
22. Singh M, et al. Non-genomic mechanisms of progesterone action in the brain. Front Neurosci. 2013 Sep 19;7:159.
23. Singh M, et al. Estrogens and progesterone as neuroprotectants: what animal models teach us. Front Biosci. 2008 Jan 1;13:1083-9.
24. Balasubramanian B, et al. (2008). Nonclassical mechanisms of progesterone action in the brain: II. Role of calmodulin-dependent protein kinase II in progesterone-mediated signaling in the hypothalamus of female rats. Endocrinology 149, 5518–5526.
25. Liu B., Arbogast L. A. (2009). Gene expression profiles of intracellular and membrane progesterone receptor isoforms in the mediobasal hypothalamus during pro-oestrus. J.Neuroendocrinol. 21, 993–1000.
26. Intlekofer KA, Petersen SL. Distribution of mRNAs encoding classical progestin receptor, progesterone membrane components 1 and 2, serpine mRNA binding protein 1, and progestin and ADIPOQ receptor family members 7 and 8 in rat forebrain. Neuroscience. 2011 Jan 13;172:55-65.
27. Jodhka PK, et al. The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression. Endocrinology. 2009 Jul;150(7):3162-8.
28. Cai W, et al. Two different molecular mechanisms underlying progesterone neuroprotection against ischemic brain damage. Neuropharmacology. 2008 Aug;55(2):127-38.
29. Castrogiovanni D, et al. Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone. Nutrients. 2012 Aug;4(8):1137-50.
30. Flock GB, et al. Activation of enteroendocrine membrane progesterone receptors promotes incretin secretion and improves glucose tolerance in mice. Diabetes. 2013 Jan;62(1):283-90.
31. Ordóñez P, et al. 17beta-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):287-94.
32. Ordóñez P, et al. Insulin sensitivity in streptozotocin-induced diabetic rats treated with different doses of 17beta-oestradiol or progesterone. Exp Physiol. 2007 Jan;92(1):241-9.
33. Moorthy K, et al. Effect of estradiol and progesterone treatment on carbohydrate metabolizing enzymes in tissues of aging female rats. Biogerontology. 2004;5(4):249-59.
34. Bagis T, et al. The effects of short-term medroxyprogesterone acetate and micronized progesterone on glucose metabolism and lipid profiles in patients with polycystic ovary syndrome: a prospective randomized study. J Clin Endocrinol Metab. 2002 Oct;87(10):4536-40.
35. 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; 28(6):360–369.
36. Pasqualini JR. Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54.
37. Campagnoli C, et al. Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. J Steroid Biochem Mol Biol. 2005; 96(2):95-108.
38. Fournier A, et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005; 114:448–454.
39. Pasqualini JR. Differential effects of progestins on breast tissue enzymes. Maturitas. 2003; 46(1):45-54.
40. Moise M, et al. Immunohistochemical profile of the estrogen and progesterone receptors in mammary benign lesions. Rev Med Chir Soc Med Nat Iasi. 2012 Jul-Sep;116(3):875-82.
41. Singh M, et al. Non-genomic mechanisms of progesterone action in the brain. Front Neurosci. 2013 Sep 19;7:159.
42. Seifert-Klauss V, Prior JC. Progesterone and bone: actions promoting bone
    health in women. J Osteoporos. 2010 Oct 31;2010:845180.
43. Clark AP, Schuttinga JA. Targeted estrogen/progesterone replacement therapy
    for osteoporosis: calculation of health care cost savings. Osteoporos Int. 1992
    Jul;2(4):195-200.

Description

Estrogen is a foundational hormone that regulates the brain and body bioenergetics in the female body.1 There are three types of estrogen found in a female body: estrone, estradiol, and estriol. The levels of all of these hormones fall dramatically at the onset of menopause. Estrogen is produced in a woman’s ovaries and adrenal glands. An extremely small amount of estrogen is produced in men through the conversion of testosterone. Symptoms characteristic of female menopause are hot flashes, insomnia, vaginal dryness, bladder problems, difficulty concentrating and anxiety.2,3 Unfortunately, health risks, including cardiovascular disease, stroke, osteoporosis, and Alzheimer’s disease, increase in the absence of estrogen.4-6

Rapid bone loss after menopause has been attributed to the decline in estrogen production, which is essential for bone growth. In addition, the loss of estrogen can result in the development of heart disease.7 Estrogen may lower total blood cholesterol and raise HDL (good cholesterol).8 And while estrogen protects the heart,5 it also protects the brain from cognitive impairments.6,9,10

There is no doubt that estrogen can protect a woman against many of the diseases of aging and that post-menopausal women on estrogen typically feel better and stay healthier. Unfortunately, most of the estrogen that is prescribed to women is synthetic estrogen, an estrogen that is not natural to the human body. Because of this, many women develop side effects. A healthy trend these days is to avoid synthetic estrogens and prescribe natural estrogens.11-13 Human receptor sites were designed to accept natural estrogen, not a synthetic form that can cause adverse symptoms. Studies have shown that long-term use of synthetic estrogens increases the formation of breast cancer.14  In contrast, natural estrogen, especially when taken in conjunction with natural progesterone, can protect against breast cancer similar to the way it protects against uterine cancer.15 In addition, the use of estriol, which is a weak estrogen, has been shown to lower the incidence of breast cancer.

Benefits of Estrogen Replacement

• Protects against cardiovascular risks4,7,16
• Supports healthy cholesterol8
• Enhances memory and cognitive function6,9
• Decreases symptoms of menopause17
• Prevents bone loss by slowing down the process17,18
• Improves vaginal dryness and eliminates bladder problems3,19

Side Effects

Side effects of estrogen therapy are often due to estrogen dominance, meaning no progesterone is providing a counter-balance or the progesterone level is too low compared to the amount of estrogen. Estrogen dominance can result in mood swings, depression, breast swelling, fibrocystic breast tissue, craving for sweets, sleep disturbances, uterine fibroids, weight gain, acne, and water retention.

Administration

Estrogen is best administered in the natural form as an estradiol or bi-est preparation. Estradiol is the most predominant estrogen in our body and the safest to replace. Bi-est contains estriol and estradiol and is supplied orally, transdermally or vaginally.

References

1. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23994581.
2. Al-Azzawi F, Palacios S. Hormonal changes during menopause. Maturitas. 2009 Jun 20;63(2):135-7.
3. Nappi RE, Lachowsky M. Menopause and sexuality: prevalence of symptoms and
   impact on quality of life. Maturitas. 2009 Jun 20;63(2):138-41. Epub 2009 May 21. Review. PubMed PMID: 19464129.
4. Lobo RA. Benefits and risks of estrogen replacement therapy. Am J Obstet
   Gynecol. 1995 Sep;173(3 Pt 2):982-9.
5. Masood DE, et al. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab. 2010 Oct;11(8):693-714.
6. Yao J, Brinton RD. Estrogen regulation of mitochondrial bioenergetics:
   implications for prevention of Alzheimer’s disease. Adv Pharmacol.
   2012;64:327-71.
7. Kano H, et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002 May 24;71(1):31-42.
8. Persson L, et al. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):810-4.
9. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic
   systems in the brain and body. Front Neuroendocrinol. 2013 Aug 29. [Epub ahead of print] PubMed PMID: 23994581.
10. Yao J, Brinton RD. Estrogen regulation of mitochondrial bioenergetics:
    implications for prevention of Alzheimer’s disease. Adv Pharmacol.
    2012;64:327-71.
11. L’Hermite M. HRT optimization, using transdermal estradiol plus micronized
    progesterone, a safer HRT. Climacteric. 2013 Aug;16 Suppl 1:44-53.
12. Mahmud K. Natural hormone therapy for menopause. Gynecol Endocrinol. 2010 Feb;26(2):81-5.
13. Conaway E. Bioidentical hormones: an evidence-based review for primary care providers.J Am Osteopath Assoc. 2011 Mar;111(3):153-64.
14. Beral V. Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27.
15. Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009 Jan;121(1):73-85.
16. Masood DE, Roach EC, Beauregard KG, Khalil RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab. 2010 Oct;11(8):693-714.
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19. Quinn SD, Domoney C. The effects of hormones on urinary incontinence in postmenopausal women. Climacteric. 2009 Apr;12(2):106-13.

Description

Melatonin is produced naturally in the body by the pineal gland.1.2 It is a primary hormone involved in regulating the body’s circadian rhythms and female menstrual cycle.1,3,4 It also plays important roles in blood pressure regulation, seasonal reproduction, immune system health, and bone and tooth health.1,5.6

Melatonin levels are higher at night, suppressed by bright light, and decline as we age. Low levels of melatonin can cause sleep disturbances, as it is a primary component in the sleep-wake cycle.1,7 Melatonin is derived from tryptophan, an essential amino acid. When tryptophan is consumed through the foods we eat, it is converted into serotonin (a neurotransmitter) and then broken down further into melatonin at night.1

Benefits

• Has powerful antioxidant effects.1,8-11
• Promotes brain health even under challenging conditions.1,12-17
• Potentially beneficial in preventing abnormal cellular development.1,17-24
• Has immune-enhancing properties.1,25-32
• Beneficial when used peri-operatively (surrounding surgeries).1,33-41
• Promotes better sleep.1,42-46
• Helps avoid jet lag.1,47-50
• Aids in the biologic regulation of circadian rhythms.1,3,51
• Supports reproductive and follicular health in women desiring to get pregnant.4,9,52-57
• Has adaptogenic properties.58-60
• Promotes a healthy inflammatory response.61-66

Side effects

Adverse reactions associated with melatonin include morning grogginess and daytime hangover. Aspirin, NSAIDS, and beta-blockers may lead to decreased melatonin levels. Use of melatonin with benzodiazepenes, sedating antihistamines, sedating antidepressants, and other sedating drugs may cause additive sedation and increase incidence of adverse effects.

Administration

Those who use melatonin supplements to help with sleep disturbances or jet lag usually take about 3 mg at bed time. Morning drowsiness indicates a dose is too high. Dose can be increased under physician supervision to obtain a good night’s sleep.

References

1. No authors listed. Melatonin. Monograph. Altern Med Rev. 2005 Dec;10(4):326-336.
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3. Bittencourt LR, et al. Chronobiological disorders: current and prevalent conditions. J Occup Rehabil. 2010 Mar;20(1):21-32.
4. Shi L, et al. Melatonin and hypothalamic-pituitary-gonadal axis. Curr Med Chem.2013;20(15):2017-31.
5. Liu J, et al. Melatonin effects on hard tissues: bone and tooth. Int J Mol Sci. 2013 May 10;14(5):10063-74.
6. Arushanian ÉB, et al. Therapeutic potential of melatonin in oral cavity diseases. Eksp Klin Farmakol. 2012;75(6):48-52.
7. Shechter A, et al. Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder. Sleep Med. 2012 Sep;13(8):1071-8.
8. Ortiz F, et al. The beneficial effects of melatonin against heart mitochondrial impairment during sepsis: inhibition of iNOS and preservation of nNOS. J Pineal Res. 2013 Sep 30. doi: 10.1111/jpi.12099. PubMed PMID: 24117944.
9. Tamura H, et al. Melatonin as a free radical scavenger in the ovarian follicle. Endocr J.2013 Jan 31;60(1):1-13.
10. Farías JG, et al. Melatonin protects the heart, lungs and kidneys from oxidative stress under intermittent hypobaric hypoxia in rats. Biol Res. 2012;45(1):81-5.
11. Pandi-Perumal SR, et al. Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotox Res. 2013 Apr;23(3):267-300.
12. Marchetti C, et al. Melatonin protects PLPC liposomes and LDL towards radical-induced oxidation. J Pineal Res. 2011 Oct;51(3):286-96
13. Srinivasan V, et al. Role of melatonin in neurodegenerative diseases. Neurotox Res. 2005;7(4):293-318.
14. Arushanian EB, Baida OA, Mastiagin SS. Effect of melatonin on memory, individual time perception, and anxiety in young people of different chronotype groups. Eksp Klin Farmakol. 2006 Jan-Feb;69(1):21-23.
15. Rosales-Corral SA, et al. Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin. J Pineal Res. 2012 Mar;52(2):167-202.
16. Cecon E, Markus RP. Relevance of the chronobiological and non-chronobiological actions of melatonin for enhancing therapeutic efficacy in neurodegenerative disorders.Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):91-9.
17. Rios ER, et al. Melatonin: pharmacological aspects and clinical trends. Int J Neurosci. 2010 Sep;120(9):583-90.
18. Brzozowski T, et al. The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. J Pineal Res.1997 Sep;23(2):79-89.
19. Di Bella G, et al. Melatonin anticancer effects: review. Int J Mol Sci. 2013 Jan 24;14(2):2410-30.
20. Wang J, et al. Melatonin potentiates the antiproliferative and pro-apoptotic effects of  ursolic acid in colon cancer cells by modulating multiple signaling pathways. J Pineal Res. 2012 Dec 8. doi: 10.1111/jpi.12035. PubMed PMID: 23330808.
21. Wang J, et al. Melatonin suppresses migration and invasion via inhibition of oxidative stress pathway in glioma cells. J Pineal Res. 2012 Sep;53(2):180-7.
22. Cui P, et al. Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression. J Pineal Res. 2012 Mar;52(2):236-43.
23. Bizzarri M, et al. Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review. Expert Opin Ther Targets. 2013 Sep 14.
24. Hill SM, et al. Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth. Curr Aging Sci. 2013 Feb;6(1):125-33.
25. Cardinali DP, et al. Melatonin and the immune system in aging. Neuroimmunomodulation.2008;15(4-6):272-278.
26. Nasrabadi NN, et al. Expression of MT2 Receptor in Patients with Gastric Adenocarcinoma and its Relationship with Clinicopathological Features. J Gastrointest Cancer. 2013 Oct 19.
27. Jung JH, et al. Melatonin Suppresses the Expression of 45S Preribosomal RNA and Upstream Binding Factor and Enhances the Antitumor Activity of Puromycin in MDA-MB-231 Breast Cancer Cells. Evid Based Complement Alternat Med. 2013;2013:879746. doi: 10.1155/2013/879746. Epub 2013 Apr 7.
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29. Csaba G. The pineal regulation of the immune system: 40 years since the discovery. Acta Microbiol Immunol Hung. 2013 Jun;60(2):77-91.
30. de Oliveira Tatsch-Dias M, et al. The concept of the immune-pineal axis tested in patients undergoing an abdominal hysterectomy. Neuroimmunomodulation. 2013;20(4):205-12.
31. Carrillo-Vico A, et al. Melatonin: buffering the immune system. Int J Mol Sci. 2013 Apr 22;14(4):8638-83.
32. Sokolovic D, et al. Melatonin protects rat thymus against oxidative stress caused by exposure to microwaves and modulates proliferation/apoptosis of thymocytes. Gen Physiol Biophys. 2013 Mar;32(1):79-90.
33. Jarratt J. Perioperative melatonin use. Anaesth Intensive Care. 2011 Mar;39(2):171-81.
34. Maitra S, et al. Melatonin in perioperative medicine: Current perspective. Saudi J Anaesth.2013 Jul;7(3):315-321.
35. Kurdi MS, Patel T. The role of melatonin in anaesthesia and critical care. Indian J Anaesth.2013 Mar;57(2):137-44.
36. Yoshitaka S, et al. Perioperative plasma melatonin concentration in postoperative critically ill patients: its association with delirium. J Crit Care. 2013 Jun;28(3):236-42.
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38. Sultan SS. Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth. 2010 Sep;4(3):169-73.
39. Ismail SA, Mowafi HA. Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth Analg. 2009 Apr;108(4):1146-51.
40. Caumo W, et al. Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain. 2009 Jan;10(1):100-8. doi: 0.1016/j.jpain.2008.08.007.
41. Caumo W, et al. The clinical impact of preoperative melatonin on postoperative outcomes in patients undergoing abdominal hysterectomy. Anesth Analg. 2007 Nov;105(5):1263-71.
42. Pandi-Perumal SR, et al. The effect of melatonergic and non-melatonergic antidepressants on sleep: weighing the alternatives. World J Biol Psychiatry. 2008 Jan; 4:1-13.
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46. Lemoine P, Nir T, et al. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007 Dec;16(4):372-380.
47. Zee PC, Goldstein CA. Treatment of shift work disorder and jet lag. Curr Treat Options Neurol. 2010 Sep;12(5):396-411.
48. Srinivasan V, et al. Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813.
49. Paul MA, et al. Phase advance with separate and combined melatonin and light treatment.Psychopharmacology (Berl). 2011 Mar;214(2):515-23.
50. Paul MA, et al. Melatonin treatment for eastward and westward travel preparation.Psychopharmacology (Berl). 2010 Feb;208(3):377-86.
51. Gitto E, et al. Update on the use of melatonin in pediatrics. J Pineal Res. 2011 Jan;50(1):21-8.
52. Tamura H, et al. The role of melatonin as an antioxidant in the follicle. J Ovarian Res. 2012 Jan 26;5:5. doi: 10.1186/1757-2215-5-5.
53. Reiter RJ, et al. Peripheral reproductive organ health and melatonin: ready for prime time.Int J Mol Sci. 2013 Apr 2;14(4):7231-72.
54. Rizzo P, et al. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci. 2010 Jun;14(6):555-61.
55. Batıoğlu AS, et al. The efficacy of melatonin administration on oocyte quality. Gynecol Endocrinol. 2012 Feb;28(2):91-3.
56. Carlomagno G, et al. Contribution of myo-inositol and melatonin to human reproduction.Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):267-72.
57. Reiter RJ, et al. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum Reprod Update. 2013 Oct 16. PubMed PMID: 24132226.
58. Arushanian EB, Beĭer EV. Pineal hormone melatonin is an universal adaptogenic agent.Usp Fiziol Nauk. 2012 Jul-Sep;43(3):82-100. Russian.
59. Arushanian EB, Naumov SS. Comparative experimental study of the psychotropic and chronotropic activity of adaptogenic phytopreparations and melaxen. EkspKlin Farmakol.2010 Jan;73(1):7-9.
60. Smirnova AV, Naumcheva NN. Solar activity and cardiovascular diseases. Klin Med(Mosk). 2008;86(1):10-7.
61. Mauriz JL, et al J. A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J Pineal Res. 2012 May 31. doi: 10.1111/j.1600-079X.2012.01014.x.
62. Jaworek J, et al. Protective effect of melatonin on acute pancreatitis. Int J Inflam.2012;2012:173675. doi: 10.1155/2012/173675.
63. Ochoa JJ, et al. Melatonin supplementation ameliorates oxidative stress and inflammatory signaling induced by strenuous exercise in adult human males. J Pineal Res. 2011 Nov;51(4):373-80.
64. Esposito E, Cuzzocrea S. Antiinflammatory activity of melatonin in central nervous system.Curr Neuropharmacol. 2010 Sep;8(3):228-42.
65. Hardeland R, et al. Melatonin–a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011 Mar;93(3):350-84.
66. Alamili M, et al. Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model. J Crit Care. 2013 Oct 16. pii: S0883-9441(13)00326-2. doi: 10.1016/j.jcrc.2013.09.006.