Hormone Replacement Therapy (HRT) Basics

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SHOULD I TAKE HORMONE REPLACEMENT THERAPY?
What are the Risks of HRT?

  • Studies have shown increased risk of blood clots, heart attack, stroke, and gallbladder disease in women who have taken combined HRT (estrogen + progesterone) or estrogen only HRT.  Most cardiovascular events occurred in the first year of HRT use.  Also, an increased risk of breast cancer has been shown with combined HRT. A large study, the WHI,  did not show an increased risk of breast cancer with estrogen only hormone use.  In women over age 65 combined HRT has been associated with increased risk of dementia. 
  • Studies in subgroups of younger women (age 50-59) have shown only an increased risk of blood clot (1/500)  for women taking combined HRT. Pregnancy has a risk of blood clot of about 1/1000.  Birth control pill use has a blood clot risk of about 1/2500.
  • Estrogen taken alone in a woman with a uterus can lead to uterine cancer. Progesterone has the opposite effect.  Therefore, women with a uterus need both estrogen and progesterone if they are taking HRT.
  • The Women's Health Initiative (WHI) study, a large study funded by the NIH, showed an increased risk of breast cancer, blood clots, stroke, and heart attack in women who took combined HRT for 5 years compared with women who took placebo.  These women were on average 63 years old.  4% of them had had a prior heart attack, angioplasty, TIA, or stroke. 36% of them had hypertension, 13% were on cholesterol medication, 4% were on treatment for diabetes, and 11% were smokers.  Women with severe hot flashes were excluded from the study.  The drop out rate was high. 38 - 53% of the participants in the different treatment groups were no longer taking their treatment at 5 years.  Also, 11% of one placebo group (combined HRT study) and 6% of the other placebo group (estrogen only study) had started hormones by the end of the study.  The point of the study was to investigate whether HRT prevented cardiovascular events in women.  It was not a study to look at hot flashes and menopausal symptoms in the menopausal transition.  This study was done because observational studies had shown a decrease risk of coronary artery disease and improved cholesterol profile in women who had taken estrogen. The WHI was a randomized-controlled trial.  This is a better way of studying a problem. This was a study of prevention of chronic disease in aging.  It really was not about women during the few years around the menopausal transition.
  • The actual findings in the WHI were that out of 10,000 women there would be 8 more breast cancers, 7 more heart attacks, 8 more strokes, and 8 more pulmonary embolisms in the women who took combined HRT compared with the women who took placebo.

What are the Benefits of HRT?

  • Decreased hot flashes, decreased vaginal dryness, better sleep, decreased bone fractures, decreased colon cancer (combined HRT), and decreased muscle aches and pains. Decreased risk of fracture and colon cancer occurs after 5 years of use.
  • Hot flashes are very common and very variable.  Most women have hot flashes for 6 months to 2 years after the period stops.  However, others may have hot flashes for years.  

What HRT should you take?

  • The dose of hormones and type of hormones used in the WHI study are really not commonly prescribed now.  The estrogen used is called combined conjugated equine estrogen.  The formula is not available.  However, it is known to be a combination of estrogens derived from the urine of pregnant horses.  The estrogen in our bodies is estradiol and estrone.  There is also estriol which is a breakdown product of the other estrogens and is weaker.  There are products available now that are almost identical to our natural estrogens.  These can be referred to as bioidentical hormones.  These do not have to be made by a compounding pharmacy.  There are products that are regulated by the FDA.  Some women do like to use products from a compounding pharmacy -- make sure it is a quality pharmacy if you go this route.
  • Products are available that contain 17-B estradiol which is derived from Mexican wild yams.  Also, estradiol valerate, which the body converts to the active form of estradiol.  You can take estradiol as a cream, gel, patch, pill, or vaginal insert.  Taking estradiol as a patch or other skin absorption method will affect cholestrol less than taking it by mouth.
  • Progesterones can also be synthetic or bioidentical.  Micronized progesterone is a natural progesterone synthesized from plant sources and finely ground to improve absorption (Prometrium is the brand name).   Medroxyprogesterone acetate (Provera) is a synthetic progesterone structurally related to natural progesterone.  Norethindrone is a synthetic progesterone related to testosterone.
  • Bioidentical progesterone has been found to reduce sleep problems, anxiety, depression, menstrual bleeding, cognitive difficulties, and sexual function compared with medroxyprogesterone acetate.  These data are limited, but it can be worth it to try micronized progesterone if you're feeling a little "PMS-y" on another progesterone.
  • All progesterones act in the lining of the uterus to inhibit the action of estrogen and prevent uterine cancer.  However,  in laboratory studies bioidentical progesterone decreases the estrogen effect on breast tissue, whereas synthetic progestins increased estrogen stimulated breast cell activity. Large studies in Europe have shown that bioidentical estrogen therapy alone does not increase the risk of breast cancer, but synthetic progesterone does increases the risk.  A study in France in which women used bioidentical estradiol and progesterone had no increased risk of breast cancer.  
  • After the menopause our testosterone levels stay pretty even unless we have had our ovaries removed.  In that case it may help to try a testosterone cream or gel.  The androgen (larger category of hormones that includes testosterone) that drops after menopause is androstenodione.  This mostly comes from the adrenal.  You can take DHEA (dehydroxyepiANDROSTENODIONE) as a vitamin.

Can I make this simpler?

  • If you are having menopausal symptoms (hot flashes, insomnia, vaginal dryness) that are bothering you, then you need some estrogen.  If you have had breast cancer, heart attack, stroke, history of deep vein thrombosis or pulmonary embolism then you need to avoid estrogen, but you may be able to try micronized progesterone.  
  • Try bio-identical estrogen.  Estrace is a micronized 17-B estradiol that is a pill.  Estrace also comes in a vaginal cream.  Using a vaginal cream 2 or 3 times a week in the vagina, or a tablet (Vagifem, or ring (Estring) will help keep the vulva and vagina skin plump and stretchy.  There are a lot of patches that contain micronized 17-B estradiol (Alora, Climara, Esclim, Estraderm, Vivelle, Vivelle-Dot).  Estrogel is an estradiol gel.  Estrasorb is an estradiol topical emulsion.
  • If you have a uterus (and some would say cervix) then you need progesterone in addition to estrogen.  Try Prometrium (micronized progesterone -- But it is made with peanut oil -- so you can not take it if you have a peanut allergy).
  • Consider testosterone gel or cream if you have had your ovaries removed.
  • Consider a DHEA supplement.
  • Take the lowest dose that makes you feel better.  Adjust the dose down with time.  The dose that will protect your bones is very small.  When hot flashes start you will need a higher dose then after a year or two you may be able to decrease the dose.  The goal is not to bump your hormone blood levels back to premenopausal levels.  The goal is to feel better.  Blood tests do not really help adjust hormone levels.  It's good to check a basic panel when you start and this should include a test of thyroid function.  However, the hormone dose should be adjusted to your symptoms.
  • Get a mammogram yearly.  
  • Pay attention to cardiovascular risk factors: family history, hypertension, diabetes, high cholesterol, and smoking.

Please talk to your doctor.  This website is meant as information only so that you can have an informed conversation with your doctor.  This is not meant to be a substitute for medical care and advice.