Bioidentical, Commercial, Pellet, Oh my! Forms of HRT Explained
Most of what will be discussed in this blog is marketing. Why? There is only so much science to go around. The female sex hormones were discovered in the early part of the 20th century and we quickly deduced the actions of each of these hormones. They were dubbed sex hormones because they absolutely played a role in reproduction. However, its something of a misnomer because there are receptors for these hormones in almost every tissue in the body. That’s partly why when you are a preteen and hit puberty everything changes and when you hit (peri)menopause it feels like all of you falls apart.
The most dominant of the female hormones is testosterone. Yeah, that wasn’t a typo. We have more testosterone than any of the other sex hormones. (If you’ve ever read your labs, you may wonder about that, but they are measured in different units.) Testosterone is responsible for our sex drive, but also impacts bone health, muscle formation, core strength and hair growth and development. Our blood levels go up and down throughout the month paralleling estrogen production. There’s a reason we want to have sex when we ovulate. Estrogen is next up. It is resposible for thickening the lining of the uterus in preparation for an embryo to arrive, but also is what makes breasts show up and hips get wider in the pubertal years as well as helping form the adult skeleton. It’s also responsible for making the adult vagina lubricated, stetchy and able to have “relations.” Progesterone is our mothering and calming hormone. It makes the lining of the uterus change from the growth phase under estrogen to a stabilized secretory phase that can let an embryo implant. It also helps us sleep at night and fight off anxiety. I personally think it’s the dysregulation in this hormone that causes most of the perimenopausal symptoms.
So, now that we know the basic players, what’s in HRT? Testosterone is generally the same in every formulation. There is no commercially available testosterone only product for women. (Estratest is a combination estrogen/testosterone oral supplement that generally isn’t the best way to get either product.) What are the options for women who need to replace their most dominant hormone? You can use a product for men and try to get 1/10th the dose - very challenging when the instructions are apply one pump to skin daily. You can get something compounded in either a troche (lozenge), topical cream or oral supplements. This is my preferred dosing. There are also injectable versions and pellets. The injectable is usually given weekly and pellets monthly. My real problems with these versions is that because they are supposed to last for a long period of time, they have to be dosed such that you get more than you need at the beginning and then by the time it’s time to redose your levels are really falling.
Estradiol is the most potently active of the many forms of estrogen we make. One of the early forms of estrogen was premarin (PREgnant Mares, urINe) which was derived from the pee of pregnant horses. There are approximately 11 forms of estrogen. This was the primary hormone used in the Womens Health Initiative (WHI) and is about 10x more likely to cause a blood clot than plain estradiol. It’s likely repsonsible for the first year bump in heart attack/stroke risk that was seen in the WHI, though the risk evened out in the second year and was reduced in the third and beyond. (For anyone concerned, this is why we don’t start women who are 20 years postmenopausal on HRT, but that’s what they did in the WHI). Bioidentical Estradiol and Bi-est are plant derived estrogens with estradiol being just estradiol alone and Bi-est being a combination of estradiol and estrone - a much weaker estrogen. It can be delivered in oral capsule, troche and topical cream. It’s usually one of these that are in pellets, but that’s more a form of administration than a particular estrogen. We also have straight up lab made estradiol that is chemically identical to the estrogen you make in your body. It can be delivered a pill, a vaginal ring, a topical cream, a mist and most commonly - a patch. Vaginal estradiol and vaginal premarin are both low dose preparations that are not absorbed systemically and something I think of separately from HRT because it only for treatment of genitourinary symptoms of menopause. Just to note, the hormone in birth control is ethinyl estradiol - a synthetic estrogen that is very potent and also about 100x more likely to cause a blood clot than naturally produced estrogen.
Progesterone is most commonly given as an oral capsule and this is my favorite form for anyone with sleep disturbance or anxiety as only oral formulation cause the sleep effect - make sure you take it at bedtime. It can also be given as a topical cream and a pellet. There is a commercial estrogen-progesterone patch version - combipatch - and is so expensive that I’ve only ever had one person take it. Bioidentical is plant derived, but really just a marketing gimmick. We have the same pellet problem here as elsewhere, though this seems less noticable than the estrogen and testosterone effects. There are generic versions - medroxyprogesterone acetate and norgestimate and these should be avoided in the postmenopausal crew especially since there is now an affordable generic of prometrium (straight up progesterone).
Let’s talk cost. I’ll do my best here, but talking cost in medicine is often like trying to follow a story from my 4 year old. It’s so mish mash that you can only guess what’s true. So, let’s assume an uninsured person is checking good RX for the commercial and what I’ve had patient’s told me for the bioidentical:
Commercial oral estradiol and oral progesterone - about $18-55/month.
Commercial estrogen patch (generic) and oral progesterone - about $125-250/month
Combipatch - $268-291/month
Femring - $980/ 3 month ring ($327/month)
Commercial testosterone injection - $32-95/month
Generic Androgel - $91-140 for 30 packets, but you have to figure out how to use 1/10th of a packet.
Compounded Estradiol/Progesterone/Testosterone - at the compounding pharmacy I use - $55-65/month (or something close), but I’ve heard numbers as high at $300-400/month.
Pellets - $300-500/every 3 months
As you can see from the numbers above, there is a wide variation in cost. All of the above products accomplish roughly the same thing. What’s my scientific recommendation? If you need the testosterone, go compounded. If you don’t, and you can get an estrogen patch at a reasonable price (many people’s insurance will cover it) that’s the direction I would go. If not, then a topical compounded formulation without testosterone would be my choice. I have a number of people who prefer one over the other, but I don’t have a strong preference because they should theorhetically do the same thing.
Final thoughts - the damage done to women’s hormone therapy by the Women’s Health Initiative and the false narrative that HRT causes breast cancer that was never borne out by the evidence in the trial cannot be understated. For reasons beyond anyone’s understanding, the further decision to label all estrogen products with a black box warning saying they caused stroke and breast cancer further destroyed industry’s desire to bring HRT products to market and limited further study. Women were told to suck it up for face the risk of what became the biggest health fear of the last 20 years - breast cancer. Enter the charlatains, nutraceuticals and gimmickery. There’s everything from something you ferment under the bathroom counter to unregulated supplements packed with plant estrogens that are “safe and natural”. Most recently, I’ve seen the rise of HRT only clinics that do lots of expensive testing to sell even more expensive hormone products. And since YouTube has roughly guessed my age, I get tons of advertising for every new HRT trend and supplement. One of the interesting statistics from the recent FDA panel is that the average women will talk to 6 providers about her peri/post-menopausal concerns. It rings true to me because I talk to so many frustrated patients. Thankfully the FDA has reversed course and removed the class warning label. At least now I can stop recurrent UTIs in my 70 year olds without them worrying about breast cancer. What I would love to see is more rigorously performed clinical trials for longer durations in appropriate age patients so I can give better advice. In the meantime, I’ll settle for fixing the symptoms and offering patients the best science has to offer.