Hormone Replacement in Menopause: Not Just Estrogen and Not Just Patches
by Lael Luedtke, MD
Menopause and its associated impacts on women’s health have finally emerged from the darkness in the last few years. For generations, menopause has been seen as an inevitable event that must be endured. Now “the change” is recognized, discussed and investigated for the dramatic impact it has on the well-being of women as they age. You’ve probably heard it discussed in podcasts. You might have seen well funded start-up businesses focusing on menopause treatment. But what does the science tell us about what is effective to help women navigate this change?
Unfortunately in many people’s minds the issue gets distilled down to night sweats and hot flashes, with a simplistic solution: slap on an estrogen patch. The consequences of menopause are far more complex, and so is the most appropriate treatment. Let’s walk through that.
Three Main Hormones, Acting Uniquely for Each Woman
Estrogen, progesterone and testosterone are the main sex hormones present throughout a woman’s life, and their presence or absence has huge impacts on health due to their action on multiple tissues within the body. A helpful framework for understanding the hormonal changes in a woman’s life after puberty is to divide that time into three eras: reproductive, peri-menopause and menopause. During the reproductive years, a woman’s ovaries are fully functioning, and she is having typical cycling in response to two primary hormones: luteinizing hormone and follicular hormone from the pituitary gland in the brain. During this time, estrogen and progesterone levels fluctuate in response to those hormones. Testosterone remains more constant and in fact, levels are typically higher than estrogen levels in a non-pregnant woman, particularly in the first half of a woman’s life.
Menopause is defined by not having a menstrual cycle for a year as the ovaries are no longer functioning, or if a woman undergoes a hysterectomy. The levels of estrogen, progesterone and testosterone all fall with menopause. The levels fall uniquely for each woman, hence the need to individualize treatment based on each woman’s symptoms and goals.
The time between the reproductive years and menopause defines peri-menopause, and the three hormones can fluctuate quite dramatically as the ovarian function waxes and wanes. This fluctuation accounts for the symptoms of peri-menopause, with some levels too high, too low or changing too quickly.
The Role of These Hormones
Receptors for these hormones are pervasive throughout the body. This is why, as women transition into menopause, they can experience wide ranging consequences. Receptors are like a lock, with a hormone as a key. When the key connects with the lock, a reaction happens. Hormones act as those keys, with the locks located on many tissues, not just sexual organs. Estrogen receptors are present on bone, brain, liver, blood vessels, skin, fat, lung and immune cells in addition, of course, to uterus, ovaries and breasts. Progesterone, likewise, can act on the brain, blood vessels and immune tissue. Progesterone plays a very specific role in the uterus and is important to use in hormone replacement in women who still have a uterus and are replacing estrogen. Testosterone influences the brain, skeletal muscle, bone, skin and cardiovascular tissues in addition to the reproductive organs.
Because all three hormones play a role in these disparate tissues, an optimal strategy would use all three to mediate the myriad consequences of menopause: emotional (depression, anxiety, irritability), brain fog, fatigue, incontinence, urinary tract infections, decreased libido, painful intercourse, weight gain, skin and hair changes, poor sleep, joint and muscle pain, fractures and of course, night sweats and hot flashes.
Historical Misconceptions Are Preventing Better Care
Given the significant impact that a decline in these hormones has on women’s health, replacement of hormones would seem to be an obvious strategy. However, a large- scale study called the Women’s Health Initiative (WHI), undertaken by the National Institutes of Health in the 1990’s, almost single-handedly put a stop to hormone replacement. The study and its conclusions were deeply flawed and have been widely refuted, but the misinformation ingrained in the minds of physicians and the public has been slow to be overcome and corrected. In fact, some of the conclusions still are promoted on the websites of nationally known medical systems. The study solely focused on a form of estrogen and progesterone almost never used anymore with important differences in how they function in the body. The inclusion criteria of the patients followed in the study created significant bias. Some data was misinterpreted, and some insignificant results were reported as significant. One of the biggest fears generated by the study results related to an increase in breast cancer. Re-analysis of the data shows a significant decrease in breast cancer risk and breast cancer mortality. Furthermore the study, in fact, verified the important improvements in bone health and quality of life.
No “One Size Fits All”
Replacing hormones can transform women’s lives in peri-menopause and menopause. Clearly estrogen generates the biggest wins, but progesterone and testosterone are vital as well to optimizing a woman’s well-being and longevity. Unfortunately no “one size fits all” prescription exists that works for every woman. The treatment must be tailored to a woman’s specific symptoms and goals to maximize results and decrease side effects.
Further, much more research needs to be done to define optimal care and specifically the longer term results. Unfortunately due to the WHI, misunderstandings and misperceptions must also be addressed. The three hormones come in a variety of forms and dosing schedules so some trial and error may be necessary to find the best regimen for an individual. Also the treatment needs to be revisited regularly to incorporate new research findings and the evolving needs of the patient.
References
Bluming AZ, Hodis HN, Langer RD. ‘Tis but a scratch: a critical review of the Women’s Health Initiative evidence associating menopausal hormone therapy with the risk of breast cancer. Menopause. 2023;30(12):1241-1245. doi:10.1097/GME.0000000000002267
Levy B, Simon JA. A contemporary view of menopausal hormone therapy. Obstet Gynecol. 2024;144(1):12-23. doi:10.1097/AOG.0000000000005553