Progesterone Intolerance - What is it?
When it comes to progesterone, most of us fall into one of three groups:
Those that Love it
Those that Hate it
Those that think ‘Meh’
The love it camp
For some women, progesterone makes them feel amazing.
It soothes their anxiety, helps them sleep like a baby and just generously makes them feel wonderful.
The hate it camp
For this group of women, progesterone is not their friend. It gives them things like greasy skin, acne, breast pain, headaches, mood changes and the thing we all really hate … bloating.
This is known as Progesterone Intolerance.
What’s the difference between progesterones and progestogens/progestins?
Progesterone is the hormone we produce in our body. Mainly from the corpus luteum in our ovary after ovulation. We also release small amounts from our adrenal glands and our placenta makes heaps of it during pregnancy.
There are synthetic versions of progesterone which are not exactly the same structure, but are very similar. These are referred to as progestogens or progestins.
What is Progesterone intolerance?
When their natural progesterone levels are high (in the luteal phase of the cycle, which is the time after mid-cycle ovulation and before you get your period), women with progesterone intolerance do not feel very good.
This is PMS (premenstrual syndrome). Sometimes this is even more extreme and women are struck with severe depression, anxiety or irritability and then we call it PMDD (presmenstrual dysphoric disorder).
If you give these women synthetic progestogens, they won’t thank you for it. Things like the contraceptive injection, the contraceptive implant and the mini-pill (progestogen-only pill) can all cause the unpleasant symptoms.
Here’s a summary of all the progestogen-only contraceptive methods available here in New Zealand:
What causes progesterone intolerance?
Synthetic progestogens don’t have exactly the same molecular structure as our natural progesterone. This means they can attach to other receptors, not just progesterone ones - this includes receptors for testosterone and aldosterone. These are hormones that are involved with water/salt retention (hence the dreaded bloating) and can also trigger acne and excess hair growth. The progestogens can also attach to progesterone receptors in the central nervous system which leads to the mood changes.
Progesterone for HRT
If you have a womb (and in some cases if you had severe endometriosis before your hysterectomy) you must take progesterone if you want to take any kind of estrogen as HRT. This is to prevent the estrogen overstimulating the womb cells which can cause them to become abnormal and even mutate into cancerous cells.
Here in New Zealand there are only four different forms of progestogen that are considered to be sufficient to protect the womb cells from being overstimulated by the estrogen part of HRT.
These are Provera tablets, Primolut tablets, the Mirena coil and Utrogestan capsules.
How can a woman with progesterone intolerance take combined HRT?
For women on HRT who have progesterone intolerance, the synthetic progestogens like Provera or Primolut can make them feel terrible.
So what can we do?
Ways to make Progesterone your friend
One option is to try the Mirena instead. Although this also contains a synthetic not bio-identical form of progestogen (levonorgestrel), because it is placed directly in your womb, there is less chance of it having effects outside your womb, so some women get on better with it.
But there are some of us for whom our progesterone intolerance is so, well, intolerant! that even the Mirena causes us grief.
Step aside Mirena, here comes Utrogestan
Many women who have suffered with progesterone intolerance find oral Utrogestan to be a breath of fresh air.
This is the only prescribed bio-identical/body-identical progesterone available in New Zealand. It contains micronised progesterone. It is better than the bio-identical hormones from compounding pharmacies because it is fully regulated (see here for more information on bio-identical hormones)
Many women feel better taking Utrogestan than when they take synthetic progestogens. Because it is bio-identical, it has the same molecular structure as our natural progesterone, so it has a strong attraction to our progesterone receptors. This means it’s much less likely to wander off and hook up with the wrong receptors.
For more information on Utrogestan see here.
What if a woman still doesn’t feel good on oral Utrogestan?
If the progesterone intolerance continues on oral Utrogestan, the same capsules can be inserted vaginally instead. This route of administration can often lead to less side effects and suits some women much better.
And if vaginal Utrogestan doesn't work?
There are a small number of women who continue to struggle with side effects even when they use vaginal Utrogestan.
When this happens, and the woman would still like to take HRT, then there are the following options:
Shorter progesterone duration
Sometimes the duration of progestogen can be reduced to 10 or even 7 days per month. This however does increase the risk of womb cells becoming overstimulated by the estrogen, so is not often done.
Long Cycle HRT
This involves only taking progesterone every 3 months instead of once a month. The problem with this approach is that quite high doses of progestogens are needed to compensate for the longer intervals, which then makes the intolerance symptoms worse while on the progestogen. It also may not provide enough protection of the womb cells because there are longer periods using estrogen unopposed.
This is an oral tablet that contains a synthetic estrogen combined with bazedoxifene which is a SERM (selective estrogen receptor modulator). These are medications that act like estrogen in some tissues but block the effect of estrogen in other tissues. Bazedoxifene has a strong anti-uterus effect (so prevents estrogen from overstimulating the womb), it is neutral on the breast (neither activates nor blocks estrogen receptors there) and is pro-estrogen in bone (so helps reduce osteoporosis). It causes hot flushes if given on its own though, so has to be paired with an estrogen to avoid this.
This is an oral tablet that contains three different synthetic steroid compounds; one has estrogen-like effects, one has progesterone-like effects and the other has testosterone-like effects.
This is a last resort management strategy for progesterone intolerance. But there are some women whose menopausal symptoms are so severe and all other non-HRT treatments and lifestyle approaches have not been helpful that they make the huge decision to have a hysterectomy and sometimes even a bilateral oopherectomy (removal of both ovaries) so they can take estrogen-only HRT.