The Progesterone Puzzle: We Have Some Explaining To Do!

When women think of hormone therapy, the first thing that comes to mind is usually estrogen. Estrogen is often the hormone of praise ("It got rid of my hot flashes!") and blame ("My mother took estrogen, and she got breast cancer!"). Its virtues and faults are debated endlessly online and in the media. Progesterone, the other hormone usually included in a perimenopause or menopause hormone plan, has its fans and detractors as well. But what is progesterone? And why would women in midlife want or need to take it?

Some Terminology

Progestogen is the umbrella term for any substance that produces progesterone-like effects in the body. It is a broad category that includes naturally occurring progesterone and many synthetic products. A progestin is a synthetic compound designed to produce some or all of progesterone's biological effects. Progesterone is the hormone produced naturally in the ovary by the corpus luteum, a cyst that forms after ovulation. Progesterone is also produced by the placenta during pregnancy.

Of note: The term synthetic does not inherently mean "worse" or "dangerous." A synthetic ingredient is chemically identical or similar to a natural one. The word natural also does not imply that something is somehow "better" or "safer," including in discussions of hormones.

In everyday conversation, the words progestogen, progestin, and progesterone are often used interchangeably, but they are not technically identical.

Why Do Women Taking Estrogen Need a Progestogen?

Estrogen stimulates the lining of tissue inside the uterus, called the endometrium, to grow. If a woman with a uterus takes or uses estrogen without enough progestogen to counteract it, this can eventually result in a dangerous proliferation of endometrial tissue that can lead to cancer. Progesterone and other progestogens can protect the endometrial lining from growing too thick. The products that have been found in clinical studies to counteract the effects of estrogen on the uterus include:

1. Oral micronized progesterone, known by the brand name Prometrium.
2. Medroxyprogesterone acetate, known by the brand name Provera.
3. Norethindrone acetate, known by the brand name Aygestin.
4. An IUD placed in the uterus that releases levonorgestrel, known as a Mirena or Liletta.
5. Other less commonly used progestogens, such as drospirenone, megestrol, and etonogestrel, which are used for specific clinical scenarios.

Some progestogen regimens are adequate for contraception but would not automatically work to protect the endometrium from thickening.

Progesterone was discovered in the 1930s. This led to the knowledge that after ovulation, a cyst forms in the ovary called the corpus luteum, which is the production center for progesterone. Progesterone was found to be essential for implantation and for maintaining a pregnancy. Natural progesterone was difficult to use as an oral medication because it was poorly absorbed, so synthetic products were developed that would have progesterone-like effects but could be taken orally. The progesterone molecule was eventually reduced in size and suspended in oil, leading to better oral absorption.

The synthetic forms of progesterone, called progestins, were able to be used in oral contraceptives (birth control pills), as treatment for endometriosis and bleeding, and in perimenopausal and menopausal hormone therapy regimens.

The hallmark of perimenopause is the irregular production of hormones by the ovaries. Since progesterone is produced in the ovary after ovulation, it makes sense that as we age and ovulation becomes less frequent, our ovaries produce less and less progesterone. This happens while estrogen levels are still fluctuating wildly. The combination of irregular estrogen production and declining progesterone can cause irregular menstrual cycles, mood changes, sleep disturbances, and infertility. In perimenopause, progestogens are not just an "add-on" to estrogen. They may be used to manage irregular bleeding, provide contraception, and sometimes stabilize perimenopausal mood swings.

While progestogens alone are not usually the primary treatment for vasomotor symptoms (hot flashes and night sweats), perimenopausal women who are still having periods, although irregularly, may benefit from starting with a progestogen for cycle control and perhaps adding estrogen later if vasomotor symptoms persist. A woman in perimenopause may still be occasionally ovulating, and if pregnancy would be undesired, progestogens can be used for contraception during this phase of life. However, contraceptive pills are not automatically considered interchangeable with menopausal hormone therapy.

There are many approaches in perimenopause that can successfully treat vasomotor symptoms while controlling irregular or heavy bleeding and assisting with mood and sleep. Working with a midlife health care specialist can provide an array of hormonal combinations to relieve perimenopausal symptoms.

The goal is not simply to replace what the ovaries are no longer making. During perimenopause, the goal is often to manage an increasingly unpredictable hormonal environment by providing symptom relief, contraception if needed, and stability. The solution might just be found in the right progestogen, whether in micronized progesterone or one of its synthetic cousins.