Getting Started on Menopause Hormone Therapy

Regimens, doses, and key questions to get you started

I think this is the post many of you have been waiting for!

In many ways, getting started on menopause hormone therapy (MHT) is not that complicated because there are a couple of go-to starter regimens. But as is the case with many things in medicine, there are some nuances, and one size doesn’t fit everyone. Therefore, I think it’s good to know the basics (and even more advanced information) about hormone combinations and doses to get the most evidence-based care that suits your specific needs. Being informed can also protect you against disinformation about estrogen doses and regimens. Sadly, some providers inaccurately promote estrogen as a wonder drug and give very high doses or lead people to think that’s what they should be taking, which can create safety issues. It’s important to know that all the information we have about the safety of hormone therapy is based on the use of standard doses. So, if you exceed the standard doses, you are marching into unknown and potentially unsafe territory. 

We’ve addressed the background information on MHT, such as reasons to take it and safety considerations, in some detail in several previous posts, so if you are new to this series or want a refresher, you can find a Table of Contents for that information here.

There are A LOT of Products

Like a lot (at least there are in the United States). Think The Cheesecake Factory menu number of products. (For those of you unfamiliar with the Cheesecake Factory, it is a chain restaurant with a menu that seems like it never ends).

There are estrogens, such as estradiol, ethinyl estradiol, Premarin, or estetrol. The estrogens can be administered via a patch, pill, vaginal ring, or topicals like gels or lotions. 

If a progestogen is needed, then there is a decision you will need to make between progesterone or a progestin. Progesterone is taken orally, although some people also use it vaginally (there is less data here). And if a progestin is used, there are pills, a patch, and the IUD. And, of course, there is a selective estrogen receptor modulator, bazedoxifene, available combined with Premarin for those who don’t want to take or can’t take progesterone or progestins. Read here if you need a primer on the difference between progesterone and progestins.

And there are also combined products. Oral estradiol with progesterone, Premarin with a progestin, and two different estradiol patches with a progestin, not to mention all the different estrogen-containing oral contraceptive pills. 

So yes, there are a lot of permutations and combinations, and it’s easy to see how it could be overwhelming.

A Word About Estrogen Doses 

The amount of estradiol in the blood during the menstrual cycle averages out to about 100 pg/ml a day, which is approximately the blood level achieved with a 100 mcg patch. This is why, for women with primary ovarian insufficiency or surgical menopause before the age of 40, we generally recommend a 100 mcg estradiol patch (or an equivalent dose taken by mouth). Because, in this situation, we want to replace what is missing. However, estrogen levels don’t need to be this high to treat hot flashes night sweats, or to protect the bones, and so the amount of estrogen needed for women ages 45 or older is typically less.

While estradiol levels don’t correlate well with hot flashes, in the KEEPS study, an estradiol level of 44 pg/ml was associated with an almost complete resolution of hot flashes, and this is the dose that would approximately come from a 50 mcg patch. Another study looking at oral estradiol found that a 50 pg/ml estradiol level (achieved with a 1 mg oral dose) also significantly improved hot flashes. Estrogen levels of 40-50 pg/ml are the levels you expect to experience in the early part of the menstrual cycle, so it makes sense that a 50 mcg estradiol patch or 1 mg of oral estradiol works really well for hot flashes. Even lower doses of estradiol will protect the bones from osteoporosis. 

Estrogen doses can be divided into very low, low, moderate, and high. The low and moderate doses are the most tested for longer-term use, and studies show they work well for hot flashes, night sweats, and osteoporosis prevention.

The table below shows roughly the dose equivalents between a transdermal patch, oral estradiol, estradiol ring (the ring where the hormones enter the blood from the vagina), and oral Premarin. There are very few head-to-head studies comparing the products, so there is probably some wiggle room in deciding equivalent doses because there are different ways of looking at the equivalence. We could use estradiol levels, and while that might seem like a good idea, it’s not always the entire story. Premarin has many other estrogens, so it’s not just about the estradiol, and oral estradiol is converted into estrone, and some of its benefits come via this estrogen. We could also look at the percentage improvement in hot flashes or the effect on proteins made by the liver to decide which dose of estrogen is equivalent to another. 

Estimated Estrogen Equivalences

In the UK, there is apparently a different conversion from the estradiol patch to oral estradiol, but every US source, including the Endocrine Society and the Menopause Society, uses the patch-to-pill conversion in the table above. Also, I’ve been prescribing hormones for over thirty years, and I have only ever heard of this patch-to-pill conversion. 

A Word About Progesterone/Progestin Doses

Progesterone is the preferred starting progestogen as it is believed to be associated with the lowest risk for breast cancer, but this does not mean that hormonal IUDs or an oral progestin are wrong. We don’t really have data on the IUD and breast cancer risk for MHT, so it’s hard to provide specifics, although the general belief is the risk is quite low. While oral progestins have a slightly higher risk of breast cancer than oral progesterone, for some people, a progestin will be a safer product because progestins are better at protecting the endometrium of the uterus from cancer and are better at controlling bleeding. 

Questions and Suggestions to Consider Before Starting

What if  I still have a period?  If yes…

• If depression is the reason you are taking estrogen or one of the reasons for taking hormones, the dose of estrogen that was tested and shown to be effective is a 100 mcg estradiol patch. There have been questions about this, so I will do a deeper dive soon. 

• If you are taking MHT for hot flashes or night sweats, you need a progestin/progesterone every month. Your own periods do not protect you from the risk of cancer that is inherent to taking estrogen, meaning you should not just take estrogen.

• You can take estrogen-containing contraception or standard MHT. Standard MHT (IUD excluded) might result in more bleeding irregularities than contraception, but you really don’t know until you try. Some people don’t want to risk bleeding issues and prefer hormonal contraception; others want to try MHT (which has lower doses of estrogen than contraception) and see how it goes. A great option is estrogen plus the 52 mg levonorgestrel IUD. If you decide on standard MHT, you can take the progesterone daily or cyclic (12-14 days a month). Many people suggest taking it cyclically because we think it will result in fewer bleeding issues, but this has not been rigorously studied. 

Do I need contraception? Yes…

• If you want your hormone therapy to do double duty, the options are an estrogen-containing oral contraceptive pill or an estrogen product and the 52 mg levonorgestrel IUD. I’ll cover hormonal contraception options and switching from the pill to standard MHT in an upcoming post.

Do I have heavy and/or frequent periods? Yes…

• Oral contraception or a levonorgestrel IUD plus estrogen are likely the best options. 

• If you choose standard MHT, progestins are generally better at controlling bleeding compared with progesterone. It doesn’t mean it’s wrong to try progesterone, but it’s something to know. You can also start with a progestin, and once your periods stop, switch to progesterone. 

Am I allergic to peanuts? Yes…

• Progesterone may not be an option, as most brands are made with peanut oil. In Canada, a brand of progesterone is free of peanut oil, although it was recently recalled as somehow the pills were switched, and the peanut oil-containing ones found their way into the supposedly peanut-free bottles!?!?!?!? 

Can I tolerate progesterone/a progestin? No, every time I have tried one of these hormones, it has been a disaster…

• The best option is likely Duavee (Premarin and a selective estrogen receptor modulator). However, there are some tips and tricks, and I will post on them soon. 

Am I at higher risk for endometrial cancer? Yes…

• The best progestogen is a progestin. The primer for the difference between products and why it matters is here.  

Am I at a higher risk for blood clots or a higher risk for heart disease? Yes…

• If you are still in the safe range for taking hormones, you should only consider transdermal therapy. You can find more information here.

Am I suffering from PMD/PMDD? 

• If yes, oral contraception is likely the best option. 

Have my periods stopped, and I am under the age of 45? Yes…

• This is a diagnosis of either primary ovarian insufficiency or premature menopause. We recommend a 100 mcg patch (or equivalent dose) until age 51 (average age of menopause), and then the dose can be reduced to the moderate or low range. Some people under age 40 may need to go up to as high as the equivalent of a 150 mcg patch.

Am I over age 45 and clearly in my menopause transition or in menopause and having bothersome symptoms but with none of the concerns listed above? Yes…

• A 50 mcg estradiol patch or equivalent is enough for most people to reduce hot flashes greatly. Some people do well with lower doses. 

• The standard starting dose of estradiol is between a 25 mcg-50 mcg estradiol patch or equivalent. The higher dose works faster, so for people who are really suffering, a 50 mcg patch or equivalent is usually the starting dose. It’s not wrong to start at 50 mcg and then try to reduce later if desired. It’s also not wrong to start at 25 mcg and then work up. 

• If someone stopped their period at age 45, 46 or 47 and has severe hot flashes, I’d probably discuss starting at a 50-75 mcg patch equivalent range. But it’s never wrong to start low and work up.

• If someone went through surgical menopause at age 45, 46, or 47 and had regular cycles before (meaning they weren’t in the late menopause transition), I might start with a 100 mcg patch and then reduce the dose around age 50-51. Again, there is lots of room for discussion of doses based on symptoms and how you feel about taking hormones.

• A lot of what we do here is based on experience and training, and clearly, there is shared decision-making with your physician.

You Are Not Married to Your Hormone Regimen

What I mean by this is sometimes people get hung up or worried about making the “right” choice, but this isn’t an unbreakable vow. You can always change, although it’s a good idea to give a product at least a 4-week trial, but depending on the symptoms you are trying to treat and the dose of estrogen, it may take 6-8 weeks to see how it’s really going to work (lower doses generally take longer). Obviously, if you hate it, you can stop before then. 

Some More About Doses

The very low doses of estradiol don’t work quite as well for hot flashes, but they still help some and are enough to protect bones. I typically only use this dose for someone who really wants to try estrogen and who is very concerned about or has previously had issues with hormone side effects. I’ve started some people on this dose, and then after two months, if they are still having symptoms and they don’t have negative side effects, they feel more comfortable increasing the dose. It is never wrong to start low and work up if that makes you comfortable. The other advantage of the very low-dose patch is that you can do the progesterone twice a year, which is helpful for people who don’t tolerate progesterone. I’ll address progesterone/progestin tolerance and options in a future post. 

Regarding oral progesterone, for someone taking a low to moderate dose of estradiol, we know that 100 mg of progesterone daily or 200 mg 12-14 days a month is enough to protect the uterus for most people, with the caveat that someone at high risk for endometrial cancer may be better off with a progestin. For people who are still having their period, the progesterone is taken the same way, either daily or 12-14 days a month. Sometimes, the daily progesterone can cause spotting, but you never know until you try. 

There needs to be more consideration about oral progesterone/progestin with the high doses of estradiol. The most studied regimen for a 100 mcg patch (or equivalent) is 10 mg of medroxyprogesterone acetate, a progestin, for 12-14 days a month. There is a study looking at 100 mg of progesterone daily with a 100 mcg estradiol patch, but that was not an endometrial safety study, so it didn’t look at the risk of cancer. So, for people who are using a 75 mcg or 100 mcg patch (or equivalent oral dose), the right progestogen might vary based on risk factors for endometrial cancer and personal comfort level. The options are:

• The standard dose of progesterone, 100 mg of progesterone a day or 200 mg for 12-14 days a month

• A higher dose of progesterone, 200 mg daily or 300 mg for 12-14 days a month.

• Medroxyprogesterone acetate 5 mg daily or 10 mg for 12-14 days of the month or an equivalent dose of a different progestin.

• The 52 mg levonorgestrel IUD

The ultimate choice for progesterone vs. progestin and dose depends on shared decision-making with your physician. 

The First Choice: A Three-Way Tie

The starting regimen for someone with no contraception concerns and who isn’t having bleeding issues is one of the following: 

• Transdermal estradiol in the 25 mcg-50 mcg estradiol patch equivalent range and oral progesterone 100 mg a day or 200 mg 12-14 days a month for those with a uterus. An estradiol patch is often the default as it has the most data, but the other transdermal products and the ring are fine, too. 

• Transdermal estradiol in the 25 mcg-50 mcg estradiol patch equivalent range with a levonorgestrel IUD (based on the available data, the IUD should be changed every five years). This is especially good for someone with bleeding issues, at higher risk of endometrial cancer, or who needs contraception.

• Premarin plus bazedoxifene. May have the lowest risk of breast cancer. There are no studies using this in the menopause transition, but I can’t think of a biological reason why it couldn’t be tried for someone in the menopause transition as long as there was informed consent about being off-label.

Other Good Choices

Combination patches with estradiol and progestin are good for people who can’t use progesterone because of a peanut allergy, have difficulties remembering to take a pill or who don’t want to take a pill, and/or when a progestin IUD isn’t desired. 

Oral estradiol 0.5 mg-1 mg a day and, for those with a uterus, oral progesterone 100 mg a day or 200 mg for 12-14 days a month.

Oral contraception for those who need contraception and/or have bleeding issues and a progestin IUD isn’t desired. 

I will continue to write posts spotlighting other products to build out a library of the full breadth of what is available. 

Summary

I hope I’ve wrestled all this information about getting started and doses into a cohesive piece. This gives you an idea of the most common starting regimens and some of the general thinking behind what we recommend. 

In some upcoming Menoverse posts, I’ll dive more into estrogen-containing contraceptives for the menopause transition and how to switch to hormone therapy, the different transdermal preparations, and troubleshooting when your MHT isn’t helping.  

As always, the information here is not direct medical advice. If you have questions, leave them below. I try to reply to the easier ones directly in the comments (obviously, again, not individual medical advice). For those questions that are more complex, I tuck them away to incorporate them in future posts.

Coming up next: hormonal contraception in the menopause transition and how to switch to MHT.

References

Cynthia A. Stuenkel et. al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 11, 1 November 2015, Pages 3975–4011, https://doi.org/10.1210/jc.2015-2236.

The 2022 hormone therapy position statement of The North American Menopause Society. Menopause 2022;29:767-794.

Martin KA, Barbieri RL. Preparations for menopausal hormone therapy. UpToDate. 2023.

Santoro N, Allshouse A, Neal-Perry G, et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study. Menopause 2017;24:238-246.

Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8(Suppl 1):3-63.

Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril 2016;106:1588-1599.

Converting Between Estrogen Products. The Pharmacists’ Letter/the Prescriber’s Letter. 2009:25, Number 251109.

Notelovitz M, Lenihan JP, McDermott M, et al. Initial 17β-Estradiol dose for treating vasomotor symptoms. Obstet Gynecol 2000;95:726-731.