natural and synthetic hormone replacement western university college of pharmacy jenny vu, pharmd...
TRANSCRIPT
Natural and Synthetic Hormone Replacement
Western University College of Pharmacy
Jenny Vu, PharmD 2008
Objectives
• What are hormones?• What is estrogen? What is its functions?• What is progesterone? What is its function?• Difference between a natural hormone
replacement and synthetic hormone replacement
• History of HRT• SEs, Contraindications, the risks of synthetic
estrogens and progesterone medications (synthetic HRT).
• Benefits of natural hormones replacement
What are hormones?• Works as the “couriers” in your body• Deliver messages from your brain that tell your cells what to do-
such as begin ovulation, go to sleep, or become aroused.• Keeps your body working all day.• Deal primarily with sexual functions, characteristics, and also have
thousands of other functions• Estrogen, Progesterone, and Testosterone are sex steroid
hormones that most affect women’s health, sexuality, and well-being.
• Other hormones are DHEA, cortisol• They are constantly working with each other so that your hormonal
makeup remains balanced.
Conrad Christine, et. al. A Woman’s Guide to Natural Hormones. A Perigee Book. Revised and Updated Edition. 2005.
Estrogen• Is not a single hormone• Is a family of hormones produced by your body, primarily by your
ovaries• Three most important are estrone (E1), estradiol (E2), and estriol
(E3)• E2 is the most active and is the one that most doctor prefer for
controlling hot flashes and other menopausal Sxs.• E3 is the largest one in your body and is considered generally safe
in term of breast cancer risk. It may protect against breast cancer
Conrad Christine, et. al. A Woman’s Guide to Natural Hormones. A Perigee Book. Revised and Updated Edition. 2005.
EstrogenEstrogen has 400 crucial functions in your body:• Stimulates the production of choline acetyltransferase, an enzyme, which
prevents Alzheimer’s disease• Increase your metabolic rate• Improve insulin sensitivity• Regulates body temperature• Helps maintain muscle • Helps you sleep deeply• Helps maintain the elasticity of your arteries• Dilates your small arteries• Inhibits platelet stickiness• Decreases blood pressure, LDL• Reduces the overall risk of Heart disease by 40% to 50%• Decrease wrinkles• Etc
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003.
EstrogenSxs of Decreased estrogens:• Thinner skin• More wrinkles• Decrease in breast size• Stress incontinence• Acne• Decreased sex drive• Increase in insulin resistance and possible diabetes• Vaginal dryness• Decrease memory• Osteoporosis• Urinary tract infections• Increased cholesterol
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003.
Estrogen• Has many protective affects on your brain. Without estrogen, your
memory usually declines. • A recent study conducted on 1889 older women in Utah revealed
that women who had taken HRT were 40% less likely to develop Alzheimer’s disease. Furthermore, the longer they were on HRT the lower was their risk.
• Researchers have concluded that estrogen use would decrease the rate of heart disease by almost 50%
• You need estrogen for optimal health. The amount of estrogen you have is important. Too little or too much can cause symptoms or disease.
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003.
Progesterone• Is one of your sex hormones and is made in your ovaries before
menopause
• Plays a vital role in maintaining your health:-improve sleep-has a natural calming effect-eliminate water retention-improves the body’s ability to use and eliminate fats-lower high blood pressure-stimulates new bone formation-protect against breast cancer-normalizes your sex drive-regrow scalp hair in women
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003.
Conrad Christine, et. al. A Woman’s Guide to Natural Hormones. A Perigee Book. Revised and Updated Edition. 2005.
ProgesteroneSxs of decreased progesterone:• Anxiety• Depression• Irritability• Mood swings• Insomnia• Pain and inflammation• Osteoporosis• Decreased HDL• Excessive menstruation
Remember that progesterone is natural hormone while progestin or MPA is a synthetic hormone. They are different.
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003
Difference Between Nature vs. Synthetic Hormones
• Nature Hormones (NH) are the same chemical structure as the ones that your body made
• NH is also called bio-identical hormones• NH are synthesized from wild yam or soy and match
your own hormones exactly• NH work in your body in the same manner as your own
hormones• NH don’t interfere with your body’s own hormone
production• Natural progesterone is synergistic and increases the
protective affects of estrogen on your heart• Natural HR don’t have the same SEs and long-term risks
like synthetic HR
Difference Between Nature vs. Synthetic Hormones
• Synthetic estrogens are artificial, or not found in nature, and are created from various sources, such as horse urine, or plants
• Premarin: most commonly prescribed HR, is a mixture of estrone, sodium equilin sulfate, contains horse estrogens, equilin and equilenin, and additives that are synthetic. These additives cause some SEs including: burning in the urinary tract, allergies, joint aches, and pains.
• Premarin contains many form of estrogen that do not fit into the estrogen receptors in your body. Your own estradiol are eliminated from your body within a few hours. Conversely, equilin (estrogen derived from the urine of horses) has been shown to stay in your body for up to13 weeks. This is due to the fact that your enzymes are designed to metabolize your own estrogen and not equilin
• Premarin can cause endometrial cancer
Difference Between Nature vs. Synthetic Hormones
• Synthetic progesterone is called progestin. It is very different from natural progesterone since it does not have the same chemical structure as the progesterone that your body makes on its own.
• Progestins were designed to mimic the actions of natural progesterone, but it don’t reproduce the actions of natural progesterone
• Progestins are contained in Provera, and Prempro/ Premphase.
Difference Between Nature vs. Synthetic Hormones
• Recent study has shown that the use of synthetic progesterone increase the risk of breast cancer by 800% as compared to the use of estrogen alone. Furthermore, an article cancer that was predicted to rise by nearly 80% after 10 years of use of estrogen-progestin (synthetic) HRT and 160% after 20 years [6]
Difference Between Nature vs. Synthetic Hormones
• Dr. Stephen Sinatra, a well-known cardiologist, states in his book, Heart Sense for Women, “I have found that synthetic progestins can lead to serious cardiac side effects in my patients, including shortness of breath, fatigue, chest pain, and high blood pressure.
• Progestin has many side effects and doesn’t function the same way in your body as natural progesterone. Progestins stop the protective effects of estrogen on your heart
Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone Replacement Therapy Puzzle. Healthy Living Books Inc. 2003
History of HRT
• Menopause was considered to be a disease needing treatment
• Early 1940s, Russell Marker, chemist, discovered a way to replicate human hormones by synthesizing the plant substance diosgenis, found in yam.
• He wanted to make the substance available to anyone.• No U.S. drug company would decide to market the natural
hormones because of limiting potential profit.• 1960s, doctors began prescribing estrogen therapy for
women, and millions of women began using the synthesized estrogen (Premarin).
• 1977, studies done at Kaiser Permanente Hospital in San Franciso showed that women on Premarin had a rate of endometrial cancer five times higher than that of non-users.
History of HRT
• To fix this problem, many doctors began prescribing the progestin Provera along with Premarin to protect the uterus from endometrial cancer. Also, Prempro (Premarin and Provera) drug was introduced to many women.
• 1996, Postmenopausal Estrogen/Progestin Intervention (PEPI) trial revealed that women on estrogen daily had high risk of endometrial cancer
• 1998, Heart and Estrogen/Progestin Replacement Study (HERS) found that women on estrogen/progestin Prempro had 4-5 times increase the risk of breast cancer with 5-10 year use.
• 2002, Women’s Health Initiative found that women on Prempro: ↑breast cancer after 5 years, ↑ coronary heart disease events, ↑VTE.
Postmenopausal Estrogen/Progestin Intervention (PEPI) Trial 1996
• Randomized, double-masked, placebo-controlled with 3 yrs of follow-up conducted to assess the influence of estrogen with or without progestin
• N= 596 healthy postmenopausal women• Mean age 53 (range 45 to 64)• Drug:0.625mg CEE; 0.625mg CEE with 2.5mg MPA; 0.625mg CEE
with 10mg MPA; 0.625mg CEE with 200mg MP
• Note: Conjugated equine estrogens (CEE) Medroxyprogesterone (MPA) Micronized progesterone (MP)
JAMA. 1996; 275:370-375
PEPI Results
• Women assigned to estrogens only had 11% to 27% of increased risk of endometrial cancer.
• Women on placebo and women on CEE and MPA or MP had less chance of developing endometrial cancer.
JAMA. 1996; 275:370-375
HERS Trial 1998
• Heart and Estrogen/Progestin Replacement Study (HERS)
• Randomized, blinded, placebo-controlled secondary prevention trial
• N=2763 postmenopausal women with established CHD
• Mean age 66.7 yrs ( less than 80 yo)• Drug: CEE 0.625 mg/2.5mg MPA for 4 yrs
JAMA. 1998; 280: 605-613
HERS Trial Results
• No benefit overall after4.1 years• Did not reduce overall cardiovascular risk• Increase risk for VTE: 3-Fold• Increase risk for gallbladder disease 40%• 4-5 times ↑ risk of breast cancer with ≥ 5-
10 year use
JAMA. 1998; 280: 605-613
Women’s Health Initiative (WHI) 2002
• Randomized, placebo controlled primary prevention trial (planned duration 8.5 yrs)
• N=16,608 healthy women with intact uterus• 40 Us centers from 1993-1998• Mean age 63 yrs (range 50-79)• Drug: Prempro (CEE 0.625mg/2.5mgMPA)• Duration: 5.2 yrs (early termination due to
increased invasive breast cancer)
JAMA. 2002; 288:321-333
WHI Results
Risks:• 26% ↑ in invasive breast
cancer• 29% ↑ in coronary heart
disease events (CHD)• 41% in CVA (stroke, MI)• Double risk of venous
thromboembolic (VTE)Benefits:• 37% ↓ in colorectal cancer• 33% ↓ in hip fracture• 24% ↓ in total fracture
JAMA. 2002; 288:321-333
WHI: Clinical Implication
• Long-term estrogen plus progestin therapy failed
to preserve health and prevent common disease in postmenopausal women
• Combination HRT increases breast cancer and
cardiovascular disease events• Combination HRT is NOT a viable intervention
for primary prevention of chronic diseases
Synthetic Estrogen (Premarin): SEs
• Breast Tenderness• Weight Gain• Fluid Retention• Headache – some migraines are estrogen
related• Nausea• GI upset• Heavy withdrawal/bleeding• Decreased libido
Synthetic Estrogen (Premarin): SEs
• Increased risk of gallstones• Blood clots– Increase clotting factors• ACHES:– Abdominal pain (severe)– Chest pain– Headache– Eye problems (vistual disturbance)– Severe leg pain
Synthetic Estrogen: SEs
• Risk of breast cancer in postmenopausal
women:
– No increased risk < 5 years use
– > 35% increased risk > 5 years use
– Increase risk with E+P combination
Synthetic Estrogen (Premarin): Contraindications
• Hypersensitivity to estrogens• Venous thromboembolic disorders (DVT, PE)• Arterial thromboembolic disease (Stroke, MI) • Estrogen-dependent cancer• Breast cancer• Undiagnosed abnormal genital bleeding• Hepatic dysfunction or disease• Pregnancy (Category X)
Synthetic Estrogen: US Boxed Warning
• Estrogens with or without progestin should not be used to prevent coronary heart disease
• The risk of dementia may be increased in postmenopausal women
• Unopposed estrogens may increase the risk of endometrial carcinoma in postmenopausal women
Sythetic Progesterone (Progestin/ Provera): SEs
• Central nervous system: dizziness, HA, nervousness
• Decrease libido
• Menstrual irregularities
• Abdominal pain/ discomfort, bloating, nausea
• Edema
• Depression, fatigue, insomnia
Synthetic Progesterone (Progestin/ Provera): Contraindications
• Hypersensitivity to MPA• VTE (deep vein thrombosis (DVT) or
pulmonary emboli (PE))• Cerebral vascular disease• Severe hepatic dysfunction• Carcinoma of the breast or genital organs• Undiagnosed vaginal bleeding• Pregnancy
Sythetic Progesterone (Progestin/ Provera): Black Boxed Warnings
• Prolonged use of Provera may result in a loss of bone mineral density
• Long-term use (ie, ≥2 yrs) should be limited
• Use caution with cardiovascular disease• Progestin and estrogen combination may
increase the risks of HTN, MI, stroke, PE, DVT
• May cause glucose intolerance in DM pts
Premphase/ Prempro (Combination of E+P Products): SEs
• CNS: HA, dizziness, pain, depression• Breast pain, dysmenorrhea• Abdominal pain, nausea• Back pain• Infection, flu-like syndrome• Peripheral edema• Vaginitis, vaginal hemorrhage• Weakness, leg cramps• Adnormal vaginal bleeding, amenorrhea• Hypertension, triglycerides increased• Libido changes• Pancreatitis, cholelithiasis
Premphase/ Prempro (Combination of E+P Products): Contraindications
• Hypersensitivity to conjugated Estrogen, MPA• Undiagnosed abnormal vaginal bleeding• VTE• Arterial thromboembolic disease• Breast cancer• Estrogen-dependent tumor• Hepatic dysfunction• Pregnancy
Premarin/ Provera and Synthetic Hormones: Long-term risks
• Breast cancer• Endometrial cancer• Ovarian cancer• Gallbladder disease• Liver disease• Stroke• Blood clots
Conrad Christine, et. al. A Woman’s Guide to Natural Hormones. A Perigee Book. Revised and Updated Edition. 2005.
Greater Benefits of Natural Hormone Replacement
• Match your own hormones exactly• Leave the body more quickly than
synthetics, thereby not posing the same health risk like synthetic HR
• Don’t have the side effects of synthetic HRT drugs if used at the proper dosage
• Natural mood enhancers (progesterone provide this benefit, while progestin can’t)
• Don’t have long-term risks as synthetics
Greater Benefits of Natural Hormone Replacement
• Are much safer than synthetic HR
• Don’t inhibit the benefits of estrogen on lowering cholesterol, as does a progestin
• Natural progesterone will not cause you to bleed for duration of use of HRT, as can progestin
• Natural progesterone may protect against breast cancer
Greater Benefits of Natural Hormone Replacement
Natural progesterone affects not seen with progestins:• Helps balance estrogen• Leaves your body quickly• Helps you sleep• Natural calming effect• Lowers high BP and cholesterol• May protect against breast cancer• Increases scalp hair• Normalizes libido• Increases the beneficial effects of estrogens on blood vessel dilation
in atherosclerotic plaques• Decrease the rate of cancer• Natural antidepressantNatural progesterone offers a safer approach to HRT than synthetic
progesterone
Natural Hormone Replacement
5 reasons you should consider NHR:1. relief of Sxs (PMS, hormonal imbalance,
menopause)2. Prevention of memory loss (Alzheimer’s
disease)3. Protection against heart disease4. Bone production (prevention of
osteoporosis)5. Growth and repair (anti-aging benefits)
Natural Hormone Replacement Therapy
• Is a better and safer therapy
• Has received increasing attention since the results of the WHI studies were announced
• Will become more and more the standard hormone treatment through compounding pharmacies
Natural Hormone Replacement Therapy
• Emphasis on topical administration; avoids problems such as blood clotting that are caused by the rapid metabolism of orally administered hormones[4]
• Individualized compounded doses may be prescribed, rather than "one dose fits all" approach of conventional hormone replacement therapy[5]
Conclusions
Your hormones function as a web. The right levels of all of your hormones are needed for you to achieve optimal health.
• If you are going to use hormone replacement, than natural hormone replacements are in every sense a better choice.
References1. Smith W. Pamela. HRT: The Answers A Concise Guide for Solving the Hormone
Replacement Therapy Puzzle. Healthy Living Books Inc. 2003.2. Conrad Christine, et. al. A Woman’s Guide to Natural Hormones. A Perigee Book.
Revised and Updated Edition. 2005.3. Wright V. Jonathan and Morgenthaler John. Natural Hormone Replacement for Women
Over 45. Smart Publication, Petaluma, CA. 1997.4. Scarabin, PY; Oger E, Plu-Bureau G (2003). "Differential association of oral and transdermal estrogen-replacement therapy with venous thromboembolism risk".
Lancet 362: 428-32. 5. Romero, M (2002). "Bioidentical hormone replacement therapy. Customizing care
for perimenopausal and menopausal women". Advance for Nurse Practitioners 10 (11): 51-2.
6. Schairer C. et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 2000;283: 485-491.
7. No author. Effects of Hormone Replacement Therapy on Endometrial Histology in Postmenopausal Women The Postmenopausal Estrogen/Progestin Interventions
(PEPI) Trial. JAMA. 1996; 275:370-375.8. No author. Risks and Benefits of Estrogen Plus Progestin in Healthy
Postmenopausal Women Principal Results from the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2002; 288:321-333.
9. Hulley Stephen, Grady D. and et. al. For HERS Group. Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women. JAMA. 1998; 280: 605-613.
10. Access PDA Lexi.com on November 21, 2007.