Menopause symptoms can be terrible whether you’re pre-, peri-, postmenopausal. I need to do a lot more blogs on health factors that affect women beyond child-bearing age. Not only is it a tremendously under-served group, but it also happens to be one that regularly reads my blog. Fortunately, I dug in to the topic a little bit since several members of my groups keep asking great questions.
I’ve had a few good articles in my queue for a while now, and am just now getting to them. One that I reviewed last week was kind of eye opening. I’ve known for quite some time that the sex hormones, both female and male, follow a circadian rhythm. It makes sense, timing is critical in reproduction.
I didn’t know is that the adrenal glands are the predominant source of progesterone during the follicular phase, and for menopausal women. They appear to be the only source for both groups as well.
Circadian rhythms, stress, and progesterone
In a small study, researchers monitored 10 ovulating women and 8 postmenopausal women to determine 24-hour hormone profiles of:
- Luteinizing hormone(LH)
- Follicle stimulating hormones(FSH)
- Adrenocorticotropic hormone(ACTH)
Progesterone followed FSH levels during the luteal phase of the menstrual cycle in ovulating women. However, there was no association between LH, FSH, and progesterone.
The story changed during the follicular phase and in postmenopausal women. In these 2 scenarios, progesterone actually followed the cortisol rhythm. I don’t have permission to share the graph, but they are literally the exact same curve. In the postmenopausal women, progesterone followed ACTH output, but wasn’t measured in ovulating women.
This jibes with older data showing progesterone increases with ACTH and decreases by blocking adrenal function in postmenopausal women. This means that progesterone levels are going under tight circadian control since they follow the same rhythm as cortisol, and driven by the same mechanism(ACTH release from the pituitary).
This data underscores the importance of optimizing circadian rhythms and managing stress during menopause. ACTH follows a circadian rhythm, but can also be elevated in response to stress. A study looking at ovulating women during the follicular phase found that stress elevated both cortisol and progesterone.
Menopause symptoms, HRT and circadian rhythms
This data is interesting for a few reasons. First, it indicates that peri- and postmenopausal women should definitely fix their circadian rhythms. This helps mimic the normal progesterone rhythm from pre-menopause. Knowing that progesterone follows the same circadian rhythm as cortisol could help alleviate symptoms. It will also help optimize hormone replacement therapy.
It’s also interesting because circadian rhythms become less robust with age. As we get older, we’re more dependent on a stricter schedule of exposures to help set circadian rhythms. Even then, they’ll never be what they were when we’re young. What’s worse, hot flashes and other symptoms that come with menopause disrupt sleep, which further disrupts circadian rhythms.
This may also play a role in declining thyroid function in women as they age. Progesterone appears to play a role in regulating thyroid function. One study showed progesterone treatment increasing free T4 in women. A mechanistic study using human cells in a petri dish showed that progesterone upregulates thyroid function. Thus, a disturbed progesterone/cortisol rhythm may affect menopause indirectly by impairing thyroid function.
Finally, I can’t help but think there is a synergy in synchronizing the cortisol and progesterone rhythms with the day/night cycle. It wouldn’t surprise me if those who have the toughest time with menopause aren’t under some level of circadian disruption. I don’t know that tossing HRT on top of that type of chaos will yield very good results.
Circadian rhythms control a vast amount of our physiology. Cortisol is one of the more robust circadian rhythms. But it also adjusts to different environmental factors and this is driven by changes in ACTH output. It seems that progesterone will also follow suit, and this could have some negative repercussions in peri- and postmenopausal women.
This data can be useful to help manage the symptoms of menopause. It could also help improve the efficacy of hormone replacement therapy. It’s a lot easier to get the dosages correct with a robust and stable circadian rhythm of progesterone release, rather than one that varies from day to day.