Taking a step back, I have been an advocate for biological hormone replacement for menopausal women for more than 25 years—back when there were only a few compounding pharmacies and no conventional pharmacy preparations that were safe.

There were no conventional options because, around that time (2002), the gigantic Women’s Health Initiative released early findings that hormone replacement increased the risk of breast cancer.

A second look at that data yielded the opposite finding: estradiol replacement in menopause—then and now—has been shown to reduce the risk of breast cancer. Not a complete preventative, but if it occurs, it’s usually a manageable breast cancer.

What We Know Now

The main benefits I focus on for replacing lost hormones at menopause are reductions in:

• Alzheimer’s disease

• Cardiovascular disease (heart attacks and high blood pressure)

• Osteoporosis

• Breast and colon cancer

There’s more—but that’s enough, right?

Let’s get into some details of how we prescribe these hormones.

So far, we have all recommended topical estrogen and oral progesterone—oral because it seemed to enhance sleep issues that arise in perimenopause and menopause itself.

So, imagine my surprise when our trusted OB-GYN and prescribing expert, Felice Gersh, MD,  had a dramatic change of heart. It has evidently been well substantiated—and we’ve all missed it—that there is a better way to prescribe progesterone. (No significant change in estrogen.)

So, What’s the Deal?

(Scroll down to “Bottom Line” if this gets tedious.)

There are two problems with how we have been prescribing progesterone:

1. We’ve been giving it orally, and

2. We’ve been giving it continuously.

The Problem with Oral Progesterone

We have long known that estrogen isn’t safe when taken orally: the liver gets the first crack at it and changes regular estradiol to estrone, in various forms, which increase the risk of blood clots, raise LDL (“bad”) cholesterol, impair short-term memory, and increase brain inflammation.

So for years, we have relied on skin applications of estradiol for safe and effective replacement of pre-menopausal levels.

It turns out that progesterone is also modified by the liver—how did we not think of this before?! The literature exists, and it turns out that the liver has its way with progesterone, producing two effects:

• The primary circulating hormone, after the liver, becomes allopregnanolone

• Actual circulating levels of progesterone (needed to protect the uterine lining) are quite low—less than optimal—only about 20% of the liver’s products are actually progesterone

So, we keep increasing the progesterone dose to get a good blood level of progesterone, but at the cost of lots of allopregnanolone, which:

• Is sedating—but not through “normal” sleep, rather a medicated sleep, and

• Stimulates appetite for “high-energy” (read: high-calorie) foods, and

• While low levels of allopregnanolone stimulate brain regrowth, higher levels lead to memory decline and hippocampal shrinkage

One of the sweet effects of estradiol in menopause is that it restores blood pressure and arterial function to premenopausal health (one reason women have less heart disease than men).
It doesn’t work if you take it orally—there are fewer beneficial effects on your heart and blood vessels.

Solution: For the benefit of your brain and heart, avoid oral progesterone.
Give progesterone vaginally, in doses of 100–400 mg, either compounded (gel or suppository) or as the regular capsule provided at the pharmacy (usually used orally, but can be used vaginally).

The Problem with Continuous Progesterone

In the interest of better sleep and to prevent problematic vaginal bleeding, we have tended to prescribe higher doses of oral progesterone and have advised patients to take it continuously.

Remember that I also credit hormone replacement with reducing the risks of Alzheimer’s disease, heart disease, and osteoporosis. It turns out that for all three, it’s much better to cycle progesterone—use it half the time, and forego it half the time.

Growth: Brain and Bones

Estrogen causes the lining of the uterus to grow—too much growth is hazardous!
But the process of growing is mediated by “growth factors,” which also cause growth in brain cells and bone cells.
So—we want growth factors!

However, if you’re causing the uterine lining to grow continuously, that can create its own risks. It’s better to shed the lining periodically. You could enable shedding by stopping both hormones, but it’s enough to just stop the progesterone.

Yes, there will be some bleeding—more for younger women, less for older women.

Solution: For better brains and better bones, it’s smarter to cycle progesterone: take it two weeks on, two weeks off (or any similar spacing you prefer—I use calendar dates more than weeks, e.g., 1st and 2nd half of the month).

Bottom Line

The reasons we use hormone replacement in menopause are many. Besides keeping us more “youthful”—hard to quantify—hormone replacement reduces the risks of:

• Alzheimer’s disease

• Cardiovascular disease (heart attacks and high blood pressure)

• Osteoporosis

• Breast and colon cancer

We benefit from the replacement of estrogen and progesterone, and how we replace them determines how beneficial it is.

• Estrogen should be used as topical estradiol, yielding good circulating levels of estradiol, which is the most beneficial form of estrogen.

• Progesterone should be administered vaginally, in doses sufficient to yield good circulating levels, and should be used about half the time (cycled).

Whew—that’s a lot of back-and-forth science, but bottom line, I hope it’s all clear.

By the way, if you’ve had a progesterone refill recently, you’ll see I’ve changed the instructions—and now you know why. I have references for all of this if you’re scientifically curious—let me know!