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.
17. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002 Aug 21;288(7):872-81.
18. Gambrell RD Jr. The women’s health initiative reports in perspective: facts or fallacies?Climacteric. 2004 Sep;7(3):225-8.
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.
2. Srinivasan V, et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119(6):821-46.
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.
28. Maldonado MD, et al. Melatonin protects mast cells against cytotoxicity mediated by chemical stimuli PMACI: possible clinical use. J Neuroimmunol. 2013 Sep 15;262(1-2):62-5.
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.
37. Wilhelmsen M, et al. Anxiolytical, analgesic and sedative effects of melatonin in the perioperative phase. Ugeskr Laeger. 2011 May 16;173(20):1424-7.
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.
43. Pandi-Perumal SR, et al. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;21(12):995-1018.
44. Sánchez-Barceló EJ, et al. Clinical uses of melatonin: evaluation of human trials. Curr Med Chem. 2010;17(19):2070-95. Review.
45. Pallesen S, Bjorvatn B. Circadian rhythm sleep disorders. Tidsskr Nor Laegeforen. 2009 Sep 24;129(18):1884-7.
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.

Description

Dehydroepiandrosterone (DHEA) is a steroid hormone produced in the adrenal glands, gonads (testes and ovaries), and brain.1 DHEA is often referred to as the “mother of all hormones” because it is the building block from which both male and female hormones are produced. It is synthesized in the adrenal glands, brain, and gonads, and it is locally metabolized into other steroid hormones including androstenedione, testosterone, and 17-B-estradiol (E2).1 DHEA is absorbed from the small intestine and transported to the liver to be metabolized and distributed to the various tissues where metabolites are synthesized. DHEA production declines in your mid-thirties to forties, leading to a deficiency that can make you feel mentally and physically exhausted. Exhaustion and stress are related to an increase in cortisol levels2 and DHEA’s role in countering cortisol levels is often overlooked.3,4 Cortisol is necessary for many important functions and is related to a normal stress response. When cortisol stays too high for too long, it becomes dangerous for those tissues that respond to cortisol.5 DHEA can help to bring cortisol back into balance.6 High sustained cortisol levels are known to be associated with many stress-related conditions. Given the high levels of stress everyone seems to deal with these days, it would be wise for adults of both genders to monitor their DHEA levels. Low DHEA levels can also lead to weakened immunity and increased inflammation.7

Benefits of DHEA Replacement

• Improves function of the immune system6,8-11
• Cognitive enhancement4,9,12
• Increases energy
• Reduces body fat and cholesterol13
• Increases insulin sensitivity14
• Potent antioxidant
• Slows some of the effects of aging in women15
• Improves mood4,16
• Supports healthy bones and calcium absorption in men17,18

Side Effects

DHEA should not be used by individuals with a history of prostate, uterine, ovarian or breast cancer. Diabetics should carefully monitor blood sugar levels, as DHEA may alter glucose regulation. Use with caution in individuals with hepatic dysfunction or hypertension.

Consult your physician before supplementing with DHEA if you are taking these medications: 4-androstenedione, 4-androstenediol, 5-androstenedione, 19-4-norandrostenedione and 19-5-norandrostenediol, testosterone replacement therapy, or estrogen replacement therapy (Premarin, Estrace, etc.).

Anti-depressants: fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa).

Medicines for seizures, certain mental disorders or pain: For example, fluphenazine (Prolixin), thorazine (Stelazine), thioridazine (Mellaril), clozapine (Clozaril), haloperidol (Haldol), risperidone (Risperdal), lithium (Lithonate, Lithobid), loxapine (Loxitane), olanzapine (Zyprexa), quetiapine (Seroquel), carbamazepine (Tegretol), valproic acid (Depakote).

Administration

DHEA is usually taken orally in capsule form; however, creams or gels are also effective. DHEA can be obtained over the counter or through a compounding pharmacy. Pharmacies that compound DHEA produce a micronized, slow-release form for a more consistent serum level. Hormones obtained through a pharmacy are usually of a higher pharmaceutical grade than over the counter.

References

1. Shah AH, et al. DHEA and estradiol levels in brain, gonads, adrenal glands, and plasma of developing male and female European starlings. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2011 Oct;197(10):949-58.
2. Wolfram M, et al. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers. Stress. 2013 Jan;16(1):54-64.
3. Bauer ME, et al. Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review. Biogerontology. 2013 Feb;14(1):9-20.
4. Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on
   episodic memory, cortisol and mood in healthy young men: a double-blind,
   placebo-controlled study. Psychopharmacology (Berl). 2006 Nov;188(4):541-51.
5. Cohen S, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA. 2012 Apr 17;109(16):5995-9.
6. Buford TW, Willoughby DS. Impact of DHEA(S) and cortisol on immune function
   in aging: a brief review. Appl Physiol Nutr Metab. 2008 Jun;33(3):429-33.
7. Huerta-García E, et al. Dehydroepiandrosterone protects endothelial cells against
   inflammatory events induced by urban particulate matter and titanium dioxide
   nanoparticles. Biomed Res Int. Epub 2013 Jan 14. PubMed PMID: 23484113.
8. Szkróbka W, Krysiak R, Okopień B. [Adrenopause]. Pol Merkur Lekarski. 2008
   Jul;25(145):77-82.
9. Davis, SR, Shah, SM, et al. Dehydroepiandrosterone sulfate levels are associated with more favorable cognitive function in women. J Clin Endocrinol Metab. 2008 Mar; 93(3):801-808.
10. Maes, M, Mihaylova, I, De Ruyter, M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct; 26(5):487-492.
11. Khorram, et al. Activation of immune function by dehydroepiandrosterone (DHEA) in age- advanced men. J Gerontol A Biol Sci Med Sci. 1997 Jan; 52(1):M1-7.
12. Hampl R, Stárka L. [Dehydroepiandrosterone, “the youth hormone”, in the light
    of recent findings]. Cas Lek Cesk. 1998 Jan 12;137(1):8-12.
13. Villareal, DT, Holloszy, JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA. 2004 Nov 10;292(18):2243-8.
14. DHEA. Monograph. Altern Med Rev. 2001 Jun;6(3):314-8.
15. Genazzani AR, et al. Long-term low-dose oral administration of dehydroepiandrosterone modulates adrenal response to adrenocorticotropic hormone in early and late postmenopausal women. Gynecol Endocrinol. 2006 Nov;22(11):627-35.
16. Schmidt PJ, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005 Feb; 62(2):154-162.
17. Sun Y, et al. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate.Chin Med J (Engl). 2002 Mar;115(3):402-4.
18. Chen RY, et al. Relationship between calcium absorption and plasma dehydroepiandrosterone sulphate (DHEAS) in healthy males. Clin Endocrinol (Oxf). 2008 Dec;69(6):864-9.

Description

Pregnenolone, a steroid hormone synthesized from cholesterol, is found in the brain, gonads and adrenal cortex.

Research shows that correcting low steroid hormones can actually help to normalize cholesterol levels. Having a higher-than-ideal cholesterol level might be the body’s way of creating a precursor for the steroid hormones it needs.1,2

Pregnenolone is a precursor to DHEA, progesterone, estrogen, and testosterone. It is also imperative to cognitive function. Pregnenolone levels are highest in the brain and studies have shown that it enhances many of our mental capacities.3 Pregnenolone also benefits mood, sleep, memory, cholesterol, and cellular repair in the brain and nerve tissues.4-10 Pregnenolone enhances the release of acetylcholine, a neurotransmitter that is important to memory function.11 Individuals with memory ailments often have low pregnenolone levels. Pregnenolone can stimulate neuron function to aid memory. Studies have shown levels of pregnenolone to be lower in the brains of people suffering from Alzheimer’s disease.12

Benefits

• Promotes nerve regeneration
• Enhances memory9,13
• Improves sense of well-being14,15
• Increases energy
• Improves sleep quality9,16,17
• Reduces the harmful effects of stress18,19
• Support healthy moods13,20,21
• Supports cholesterol homeostasis1,2

Side Effects

There are no reported significant adverse effects. However, pregnenolone may be converted to steroids such as DHEA, which may cause acne, particularly in women. There are no known drug interactions.

Administration

Pregnenolone is generally administered by capsule; however, it can also be utilized in a cream or gel form. It is generally taken in doses ranging between 10–100 mg per day. Since pregnenolone is quickly converted to other hormones in the body, it is difficult to accurately measure. Therefore, as a person ages, it is typically replaced with 25–50 mg per day.

Frequently Asked Questions

Q. What changes will I notice if I take pregnenolone?
A. Some people do report an improvement in their memory.

Q. Can pregnenolone be measured by a blood test?
A. Yes it can; however, it is difficult to get an accurate measurement because it converts to other hormones quickly.

References

1. Dzugan SA, et al. Correction of steroidopenia as a new method of hypercholesterolemia treatment. Neuro Endocrinol Lett. 2011;32(1):77-81.
2. Dzugan SA, Arnold Smith R. Hypercholesterolemia treatment: a new hypothesis or just an accident? Med Hypotheses. 2002 Dec;59(6):751-6.
3. Martín-García E, Pallarés M. A post-training intrahippocampal anxiogenic dose of the neurosteroid pregnenolone sulfate impairs passive avoidance retention. Exp Brain Res. 2008 Nov;191(2):123-31.
4. Yau JL, et al. Central administration of a cytochrome P450-7B product 7 alpha-hydroxypregnenolone improves spatial memory retention in cognitively impaired aged rats. J Neurosci. 2006 Oct 25;26(43):11034-40.
5. Mayo W, Le Moal M, Abrous DN. Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations. Horm Behav. 2001 Sep;40(2):215-7.
6. Mayo W, et al. Individual differences in cognitive aging: implication of pregnenolone sulfate. Prog Neurobiol. 2003 Sep;71(1):43-8.
7. Rupprecht R. The neuropsychopharmacological potential of neuroactive steroids. J Psychiatr Res. 1997 May-Jun;31(3):297-314.
8. Steiger A, et al. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Res. 1993 Jul 2;615(2):267-74.
9. George O, et al. Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes. Psychopharmacology(Berl). 2006 Jun;186(3):402-13.
10. Mayo W, et al. Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus. Neurobiol Aging. 2005 Jan;26(1):103-14.
11. Darnaudery, M, et al. Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition. Brain Res. 2000 Jan 3;852(1):173-179.
12. Naylor JC, et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer’s disease compared to cognitively intact control subjects. Biochim Biophys Acta. 2010 Aug;1801(8):951-9.
13. Marx CE, et al. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience. 2011 Sep 15;191:78-90.
14. Barrot M, et al. The neurosteroid pregnenolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens. Eur J Neurosci. 1999 Oct; 11(10):3757-3760.
15. Carta MG, Bhat KM, Preti A. GABAergic neuroactive steroids: a new frontier in bipolar disorders? Behav Brain Funct. 2012 Dec 19;8:61. doi: 10.1186/1744-9081-8-61.
16. Darbra S, et al. Sleep-wake states and cortical synchronization control by pregnenolone sulfate into the pedunculopontine nucleus. J Neurosci Res. 2004 Jun 1;76(5):742-747.
17. Terán-Pérez G, et al. Steroid hormones and sleep regulation. Mini Rev Med Chem. 2012 Oct;12(11):1040-8.
18. Semeniuk T, Jhangri GS, Le Mellédo JM. Neuroactive steroid levels in patients with generalized anxiety disorder. J Neuropsychiatry Clin Neurosci. 2001 Summer;13(3):396-8.
19. Sripada RK, et al. Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. Biol Psychiatry. 2013 Jun 1;73(11):1045-53.
20. Ritsner MS, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010 Oct;71(10):1351-62.
21. Osuji IJ, et al. Pregnenolone for cognition and mood in dual diagnosis patients.Psychiatry Res. 2010 Jul 30;178(2):309-12.

Are you tired, irritable, having trouble sleeping? Depressed Anxious? Skin drying, suddenly gaining weight when diet and exercise haven’t changed, and libido lagging? These questions aren’t for women. They are for men. Bioidentical hormone therapy and testosterone therapy is available in Bend for men.

Men have as many issues with hormones as women, they have the same symptoms, but  it isn’t talked about as much. It’s truly unfortunate because men can benefit as much from education and bio-identical hormone therapy too.

First, men need to understand that they have more hormones than testosterone. Secondly, they need to understand that testosterone is important for overall heath, not just sexual function.

As I evaluate men’s health, i pay attention to five hormone functions: thyroid, insulin, testosterone, cortisol, human growth hormone and DHEA. All combined they regulate a man’s health and body function. Unfortunately, men don’t have a monthly ‘report card’ like women do, so it’s less clear when something or a combination of things is off track.

While women often initially cite emotional and psychological concerns like feeling anxious and depressed, men zero in on physical issues like middle-aged bulge, lack of energy or increases healing time after a minor injury. Men notice that their physical performance has changed, often they think they need to tough it out, but it’s more than enough reason to seek out some medical advise.

This is something that women can be very sensitive to, perhaps suggesting men in their lives to see a doctor. If a woman is changing metabolically, she can assume her male partner is too. It is not uncommon for a man in his 40’s and 50’s to see a significant drop in his production of testosterone, or see the thyroid function falter. Both result in symptoms like fatigue, being short-tempered, drying of skin and a vague sense of depression. But many men don’t seek help until sexual function is involved. That’s a man’s ‘report card’.

Once trouble with the prostate is ruled out, that’s when I as a specialist in bio-identical hormone replacement therapy can have a candid and comprehensive conversation about hormone balance and overall health. It’s all about goals with men once the labs are in and the numbers are on the table, most men are very willing to talk about diet exercise and treatments. Most often, they zero in on testosterone, and while improving intimacy is an important goal, hormonal balance is critical in protecting against heart disease and bone loss too. The first goal is to get the thyroid functioning at optimum levels, this gland is the traffic cop for any body, it has to be functioning well for other systems to work as they should. With that done, testosterone in the form of creams and injections can be considered. Bringing those levels up can significantly change how a man is feeling, both physically and emotionally. They will also see an increase in energy, brighter looking skin and better moods, The same feeling women experience when they are correctly balanced.

Many men are feeling the benefits of bio-identical hormone replacement therapy. Dr. Brust @ Preventative Medicine Clinic in Bend is a specialist in this area. However, don’t assume that testosterone is an easy fix. It requires consultations with the prescribing physician frequently, and having labs drawn at least twice a year, as testosterone is a controlled substance. Also don’t confuse hormonal balance with anabolic steroids, each have different goals, different dosages and different results. It’s best to focus on feeling your best regardless of your age. Men shouldn’t avoid the conversation, they should feel comfortable in seeking out options.  Testosterone is supplemented in a variety of forms: hormone pellets, creams, gels, and intramuscular injections.  To find out if this therapy is right for you, please contact Preventative Medicine Clinic in Bend @ 541-383-3424.