The Hormonal Chaos of the Menopause Transition

And why blood tests aren't helpful

Many people get blood work to tell them if they are menopausal or how far away they might be from menopause, meaning the final menstrual period, but it isn’t standard of care. In fact, all of the guidelines advise against it. The blood work that we are discussing here is estradiol, the main estrogen released by the follicles in the ovaries, and follicle stimulation hormone or FSH, a hormone released by the pituitary gland that stimulates the follicles. 

Many people, and unfortunately this includes a lot of providers, think of the menopause transition, also known as perimenopause or premenopause, as a gradual, but predictable march towards the final menstrual period. Meaning, ovulation just starts to space out, and estradiol gradually drops and FSH gradually rises. And if this is what someone believed, then I can see how that would translate to “we can track these hormones.” But this thinking is incorrect. While ultimately 1-2 years after the final menstrual period estradiol levels are lower for everyone, the process of the menopause transition, going from regular ovulation to that last period, is not steady or predictable, hormonally speaking. 

Before we start reviewing how estradiol levels change in the menopause transition, let’s review the typical ovulatory pattern. It’s always good to have a baseline. Normally, estradiol levels are low at the start of the cycle (20-40 pg/ml) during the early follicular phase and then rise, as high as 400 pg/ml or higher, during ovulation. There is a second smaller peak after ovulation during the luteal phase. 

Averaging things out, including the highs and the lows, the average daily level of estradiol is approximately 100 pg/ml. This translates to the estrogen received from a 100 mcg patch or 2 mg of estradiol by mouth. Unfortunately, there are some providers recommending doses that are higher than this in menopause, and the idea that someone would need more estradiol than their body typically makes isn’t supported by the literature, and frankly, it’s potentially dangerous. Unfortunately, I’ve seen some people who appear to be on 200 mcg of estradiol a day transdermal or even much higher.

Now back to hormone fluctuations in the menopause transition. There are four general trajectories of estrogen levels during the menopause transition, and this data comes to use from the Study of Women’s Health Across the Nation. 

• Estradiol levels rise for about 5-6 years and then drop 1 year before the final period

• Estradiol levels rise until the final period and then decline over 2 years after the final period 

• A slow decline of estradiol during the menopause transition to after the final period 

• Low levels of estradiol with no real decline

A random blood sample of estradiol, or even a few, can’t tell you which of the 4 trajectories you are on, or where you might be on that timeline. Even multiple levels can’t predict, because within each trajectory there are ups and downs and in the menopause transition these ups and downs can be chaotic.

So how does this hormonal chaos happen? 

Let’s go back to a typical ovulatory cycle. Follicle stimulating hormone or FSH triggers waves of follicles to develop during the follicular phase, and the “best” follicle from the last wave is the one that dominates. Levels of estradiol rise significantly. FSH levels also rise, but it’s less dramatic. When estradiol levels are high enough, the messaging switches and levels of luteinizing hormone or LH quickly rise (often called a surge), triggering ovulation and the luteal phase. After ovulation (during the luteal phase) estradiol, FSH, and LH levels all drop. The cells left behind after ovulation organize into the corpus luteum, which produces progesterone as well as estradiol (although estradiol levels don’t rise as high as they did during the follicular phase). If pregnancy doesn’t occur, the corpus luteum reaches the end of its life span, and progesterone and estradiol levels drop and the cycle starts again. 

Here’s how ovulation can change during the menopause transition: