The federal government’s discontinuance of the “Women’s Health Initiative,” one of the largest ongoing studies of the risks and benefits of hormonal supplementation in the periand post-menopause did not go unnoticed by women – especially those taking Premarin and Provera or other forms of hormonal therapy or supplementation.
This article will make sense of the muddle and hopefully give women some direction in determining their individual paths. It will answer the questions:
1. Why take hormones? What are the risks?
2. What are alternatives to hormones?
3. If I use hormonal supplementation, how long should I do so?
4. What are the “best” (most effective with lowest short and long-term side effects and risks) forms of hormonal supplementation?
5. Who can work with me to individualize my regimen?
First a brief definition of terms:
HRT: Hormonal supplementation therapy consisting of a combination of estrogen (the “active ingredient”) and either progesterone or a “progestin.”
Progestins are synthetic compounds inexpensively made to mimic the effects of progesterone. These provide a degree of protection against the possible development of uterine carcinoma from continuous exposure to “unopposed estrogen.”
ERT: Hormonal supplementation with estrogen only.
A phytoestrogen is a compound from a plant source which has activities mimicking those of estrogens, especially on some of the disturbing symptoms of (peri-)menopause such as hotflashes and mood/memory alterations.
A bioidentical is a compound synthesized from a plant source (usually soybeans) to be essentially the same molecule as the natural product produced from the ovaries that it was designed to supplement or replace.
WHY TAKE HORMONES?
This advice has radically changed over recent years, as more knowledge of the risks as well as benefits of hormones are clear, and as more non-hormonal agents have become available. The most immediate reason for initiating hormonal supplementation are the often severely disturbing discomforts of (peri-) menopause, including hotflashes, mood, memory and sleep problems, and disturbance in one’s “sense of well being.” These are invariably promptly and usually completely controlled by the right dose of estrogen administered in the right way (in my opinion transdermally, but a majority of women find relief in oral preparations as well). Additionally, estrogens do well in preventing excessive bone loss and in offering cardiac protection. If taken for a short term (certainly less than 2-3 years, probably up to 4-5 years), they do not increase the risk of breast cancer.
However, there is a potential short and long-term price to pay for hormonal supplementation. If you already have blood vessel disease secondary to plaque, laid down from continually elevated LDL cholesterol and triglycerides and/or genetic factors, the “blood slowing” effects of estrogens (especially oral estrogens) will increase your risk of heart attack or stroke in the short term (first 1-2 years), especially if the estrogen is taken along with a progestin, and especially if that progestin is medroxyprogesterone acetate (“Provera”). (Although of note is the fact that estrogensCespecially if taken aloneCdo confer long term cardiac protection.)
Additionally, long-term (over 5 years) administration of estrogens, especially above the “super low doses” increase the risk of breast cancer. Additionally, the risk of thromboembolism (blood clot, stroke) as well as gallbladder disease is higher in women taking hormonal supplementation.
The statistical risk (and this is calculated for oral mid-dose Premarin and Provera only) is this: If 10,000 people take “mid-dose” estrogens, combined with progestins, there will be 8 additional cases of breast cancer and severe cardiovascular disease and 9 more cases of blood clots and stroke. However, there will be 8 fewer cases of colon cancer and severe osteoporotic fractures.
ALTERNATIVES TO HORMONE REPLACEMENT THERAPY
For peri-menopausal discomforts, phytoestrogens and botanicals (red-clover and wild yam derivatives, black cohosh, chaste berry tree fruit, soy, etc.) may offer anything from a modicum of help to significant relief without sacrificing safety. The tradeoff is expense and frequently less-than-desired effect.
Exercise and proper diet always confer both protection and symptomatic relief. Vitamin E 800 mg a day can help with hotflashes, as can low-dose Effexor, a psychoactive medication sometimes used for depression. Certain high dose progestins alone can help, but do no favors for your cholesterol.
Certainly avoiding hotflashes-triggers, such as heat, spicy foods, hot drinks, alcohol, strong emotions, etc. and keeping cool, reducing stress via yoga or meditation, etc. helps as well.
A new class of compounds known as SERMs (“selective estrogen receptor modulators”) offer similar bone and cardiovascular protection as estrogens while actually decreasing the incidence of breast cancer. SERMs are synthesized compounds that mimic estrogens in their actions while causing no uterine tissue build up. Raloxifen (Evista) is the presently available SERM. Unfortunately, raloxifen in no way helps with menopausal discomforts and, in fact, may make symptoms more severe. However, when the FDA gets around to approving tibolone (used for over 10 years in Europe) and other “second generation SERMs,” American women may have finally found the nearest thing yet to the hormonal holy grail: a compound that helps relieve symptoms, inhibits bone loss, lowers LDL cholesterol, does not build up uterine lining, and diminishes breast cancer risk (look for this in 1-2 years).
HOW LONG TO USE HORMONES
If you elect to start hormone therapy because of peri-menopausal symptoms, once these symptoms have been controlled for 6-12 months, it’s probably best to taper down to the next lowest dose for a year, and then slowly taper off over the next 1-2 years.
If there are bone density issues, you may wish to substitute one of the “bisphosphonates” (alendronate or “Fosamax,” risedronate or “Actonel,” or etidronate or “Didronel”) for estrogens or start usage when you taper off.
For adverse lipids (elevated cholesterol, triglycerides), any of the “statin” drugs (Lovastatin, “Zocor,” Lipitor, Mevacor) confer protection and actually provide bone protection at the same time.
If you wish to use hormones because of a strong family history of Alzheimers, or because they “make you feel better” when you’re on them, and you elect to continue long-term, use the lowest possible dose with the lowest amount of progesterone necessary to prevent uterine cancer, and understand that you may have a trade-off of a very slightly increased risk of breast cancer.
WHICH HORMONE IS FOR YOU?
Basically, all forms of hormones (type, brand, and delivery method) are more or less metabolized into the same thing. The differences are the “stops along the way.” That said, my personal choice of compound is estradiol, and of delivery method, transdermal application.
Estradiol is a “bioidentical,” one of the major estrogens naturally produced by the ovaries. Orally, it comes in mid- and low-dose strengths and is a scored tablet, easy to break in half for dosage-tapering. Transdermally, it comes in varying size patches, including one the size of a Chicklet, with the hormone imbedded in the polymer, also making for ease in tapering by progressively cutting off portions of patch to taper down.
I like transdermals over pills because they bypass the GI tract and liver on their “first pass,” minimizing adverse symptoms. Additionally, while oral estrogens have the effect of increasing “sex hormone binding globulin,” taking some free testosterone out of circulation (sometimes adversely affecting sexual desire), transdermals have no such effect.
Transdermals are available commercially in patch form (Climera, Vivelle, Alora, Combipatch, etc.) and as creams (estriol, estradiol, estrone) which can be individually compounded by special pharmacies to meet individual needs in cases where women have had difficulty with other forms or hormonal supplementation.
With regards to progesterone, if it is needed, the natural product (oral micronized progesterone, or Prometrium, and probably 3-5% progesterone cream) or the synthesized norethindrone (or “NET”) is probably best.
WHO TO SEE FOR CARE?
Unfortunately, not all doctors are “created equal” when it comes to knowledge of hormonal, botanical, and non-hormonal regimens for health maintenance, protection and therapy in periB and post-menopausal women.
If you find your practitioner wanting in this area, you might suggest to her/him a post-grad course or update. Failing that, the best way to find a practitioner knowledgeable in periand post-menopausal women’s medicine is to find a member of the North American Menopause Society (NAMS), especially one who is “certified” as a menopause clinician. To do this, go to their web site and follow instructions to find NAMS members in your area. Look especially for the names in BOLD print, who are certified menopause clinicians.
“The Bottom Line”
The bottom line is: hormones work in the many areas described, and for short periods of time (less than 4-5 years), especially if taken alone or combined with low doses of natural progesterone or periodic progesterone/progestin withdrawal, are quite safe. But the bottom line also is that there are now also many non-hormonal alternatives in most all of these areas. So:
1. For (peri-)menopausal symptoms that are bothersome enough to warrant therapy, use either botanicals or low dose estrogens. Both are quite safe in the short term. If utilizing estrogens for symptoms, and you have not had a hysterectomy, use along with the lowest dose of natural progesterone, or NET, or utilize periodic (every 3-4 months) progestin withdrawal (utilizing either natural progesterone, NET, or Provera taken for 2 weeks every several months to “bleed off” any tissue that may have formed), or you may use estrogen only in ultra low doses following the endometrium with periodic ultrasound.
2. If utilizing estrogens for adverse symptoms, use a moderate strength product for +/- 1-2 years, tapering off over another 1-2 years. If symptoms recur during “taper,” add in one of the botanical supplements.
3. If taking estrogens to treat osteopenia or prevent osteoporosis, switch during the end of the tapering off period to a bisphosphonate or SERM. If adverse symptoms occur, add in a botanical or consider super-low dose estrogen with or without progesterone. Also important is calcium and weight bearing exercise. DHEA and/or low dose testosterone also protect bone.
4. If considering estrogen for cardiac protection (strong family history of heart disease; abnormal lipids) use a statin drug as first line therapy (these also confer bone protection).
5. If considering estrogen for Alzheimers: there is no data that estrogen lessens the risk of Alzheimers in the general population, but there is information that risk is diminished in women with a strong family history of the disease. If this is the case, especially if estrogens are helpful for other indications (see above), use the lowest dose, weakest progesterone, etc.
6. If using estrogens “just because it makes me feel better,” or “I’m so worried how I’ll feel if I go off…”: Start to slowly taper off, adding in a botanical as needed. If there are problems, you can decide to stay on ultra low dose estrogen supplementation (see above).
7. Await further developments: “New generation” SERMs are around the corner which will offer both bone and cardiac protection while allowing no increased breast cancer riskCand temper periBmenopausal discomforts at the same time.
HOW DO I TAPER OFF?
This is one of the reasons I like transdermals. You “taper off” by simply very slowly and imperceptively lowering your dose over a period of many months. For example, if you are on a 0.05 mg patch, you may taper down very slowly (e.g., a month at a time), cutting off small amounts of the patch (e.g., 10%-20%, etc.) so that after approximately 6 months, you’ve cut off 1/3 of your patch. There are five patch doses and each lower dose is approximately 25-35% lower than the previous dose. So, if you start on 0.05 mg, you’d be down to 0.0375 mg in approximately 6 months, to 0.025 mg in a year, and down to zero in 12-2 years from the time you started your taper.
For oral preparations, take your present dose and the next lowest dose and mix them all together in the bottle, starting by alternating two of the higher with one of the lower dose on alternate days, going down in several months to one of each on alternate days, and then switching to one higher-to-2 lower dose to downregulate eventually over a 6-9 month period of time to the next lower dose. If you desire to go lower still, repeat the process again (you can see why it’s easier to do this with patches or creams). If you separately take progesterone, stay with your present dose until you halve the estrogen, then halve the progesterone as well.
FOR MORE INFORMATION
To learn more about peri-menopause/menopause, check the NAMS website. To learn more about the Women’s Health Initiative, check the WHI website.
Image source: Fahad Z