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Menopause
Menopause
Menopause, which is a state characterized by reduced ovarian secretion of estrogen and progesterone and amehorrhea.
- Menopause is rare in the animal world, but humans share this stage of life with some species of whales and narwhals!
Reproductive Stages and Estrogen Levels
For simplicity, our graph will not include changes progesterone levels, which match the overall pattern of changes estrogen for our purposes.
- Stages based on fertility:
- Birth to menarche is a non-fertile stage.
- Menarche to menopause comprises the fertile stage.
- The post-menopause stage is a second non-fertile stage.
- Menarche usually occurs between the ages of 10-16, and that menopause usually occurs between the ages of 45-55.
- Perimenopause is the roughly 2-5 years prior to menopause.
- Estrogen levels during a woman’s lifetime change as follows:
- Levels are low and steady from birth to puberty.
- Puberty, which includes menarche, is a time of fluctuating but ultimately rising levels of estrogen.
- During adulthood, estrogen levels are higher and oscillate with the menstrual cycle.
- For simplicity, we’re omitting periods of pregnancy and other conditions when estrogen levels deviate from this pattern.
- In the perimenopausal period, estrogen levels start to fluctuate again, and trend downwards.
- Post-menopause, estrogen levels are relatively low and stable.
- For completion, show that the peak fertile years are when estrogen is relatively high and stable, between the post-menarche and perimenopausal changes.
Physiology of Menopause
- Menopause is often described as both an event and as a process:
- The event being the last menstrual period, which can only be identified retrospectively.
- The process being the winding down of reproductive hormones and corresponding signs and symptoms.
- The terms “perimenopause” and “menopausal transition” are more specific to this process, so we’ll use them as appropriate.
- A woman is said to be postmenopausal when she has not had a menstrual period for 12 or more months.
- Menstrual periods cease when the follicular pool falls below a critical threshold.
- Ovarian follicles are clusters of cells responsible for nurturing the ova and producing estrogen and progesterone, under the guidance of gonadotropins.
- At birth, the ovaries contain 1-2 million primordial follicles; most of these follicles undergo atresia, and a small number are ovulated during a woman’s lifetime.
- By menopause, the number of ovarian follicles has dropped to the hundreds or thousands; this is not enough to maintain the higher levels of estrogen and progesterone needed to maintain the menstrual cycle.
- The signs and symptoms associated with menopause are largely due to changes in estrogen levels; thus, they begin in in perimenopause, and some continue into post-menopausal life.
- Roles of estrogen: Urogenital maintenance; protective effects on cardiovascular, metabolic, and bone health
- For example, it’s thought that premenopausal women have lower rates of cardiovascular disease than their age-matched male peers because of estrogen’s protective effects on the arterial walls and the myocardium; post-menopausal women and men have similar rates of cardiovascular disease.
- Sources of Estrogen: The ovaries are not the only sources of estrogen, as it is also produced in the adrenal glands and adipose tissue; these are the sources of the low but stable levels we drew in our graph.
- “Natural menopause” usually occurs between the ages of 45 and 55 years old; the average age is 51 years old (this average varies somewhat by geographic population).
- “Early” menopause is when menopause occurs between the ages of 40-45 years old.
- “Premature” menopause is when menopause occurs before age 40 (learn about ovarian insufficiency).
- Causes of early or premature menopause include: primary ovarian insufficiency, genetics, autoimmune disorders, and chemo/radiation therapy.
- Menopause can be induced by surgery, chemotherapy, and some drugs that affect the hypothalamic-pituitary-ovarian axis; induced menopause is characterized by a much more abrupt decline in hormone levels.
- Earlier and induced menopause appear to be associated with higher risks of cardiovascular disease and osteoporosis.
Symptoms of Peri-menopause and Menopause
- These manifestations vary by individual, by the timing of menopause, and the time since menopause.
- As we go through these symptoms, notice that many are inter-related, in that one can exacerbate the next.
- Bleeding irregularity: One of the most obvious signs of perimenopause is increasing irregularity in a woman’s menstrual cycles; this irregularity often manifests as shorter cycles with longer bleeding.
- Hot Flashes: Aside from bleeding irregularities, vasomotor symptoms, aka, hot flashes (or hot flushes) are one of the most common symptoms of perimenopause and menopause.
- Got flashes can last a from few seconds to several minutes, and are described as a sudden sensation of heat, usually starting in the upper body and radiating towards the head.
- Sweating, clamminess, and heart palpitations may also be experienced during hot flashes.
- Sleep disturbances are also common, especially when hot flashes strike in the night.
- Brain fog, which is characterized by forgetfulness and difficulty focusing, is also reported, and is made worse by sleep disturbances.
- “Genitourinary syndrome of menopause (GSM): reduced estrogen levels contribute to vaginal dryness, itchiness, pain during intercourse, increased UTIs, and urinary incontinence.
- Changes in mood, such as increased anxiety or depression.
- Notes on symptoms:
- Most of these symptoms begin during perimenopause and subside after menopause, but some women continue to experience issues for years post-menopause.
- Some of these symptoms correspond with aging in general, such as problems with memory, sleep, and mood, so it can be difficult to know when symptoms are due to shifts in estrogen levels or other factors.
- Research indicates that menopausal symptoms are mediated by race and ethnicity, BMI, diet, smoking, overall health status, and family and community support systems as well as employment status and/or financial situation.
- Cultural attitudes towards aging and menopause can also have a significant impact on a woman’s experience of the menopausal transition and post-menopausal life. For example, women who believe that menopause signals the end of their youth and usefulness are more likely to report negative experiences than women who view the post-menopausal phase as a more independent stage of life, free from the worries and responsibilities of a menstruating, fertile woman.
Longer-term Concerns
- Estrogen has protective effects on many body systems, so we need to consider some longer-term concerns in post-menopausal women, including:
- Higher risk of osteoporosis, cardiovascular and metabolic diseases, and vulvo-vaginal health and sexual well-being.
Treatments
- Hormone replacement therapy (HRT) was designed to alleviate some of the symptoms of the menopausal transition, including vasomotor and vulvo-vaginal symptoms, and to protect against longer-term problems, including bone loss and diabetes.
- Types of hormone replacement therapy:
- The most commonly used formulations include both estrogen and progesterone; estrogen is provided to alleviate symptoms and to protect against bone loss and diabetes, and progesterone is added to protect the uterus from un-opposed estrogen (which can lead to endometrial hyperplasia and cancer).
- In patients who have had hysterectomies, estrogen-only formulations are more appropriate (as there is no need for progesterone’s uterus-protective effects).
- There is also a formulation that includes estrogen, progesterone, and androgens, but this has been less-well studied.
- However, it appears that these risks are reduced in younger women and when HRT is used soon after menopause (in other words, the risks are higher in older women and when HRT is used longer after menopause).
- Other advances in HRT pharmacology include lower levels and different sources of hormones in the formulations, and more options for administration, including oral tablets, skin patches, gels, and vaginal rings.
- Hormonal replacement therapy is contraindicated in patients who have or have had some cancers, especially breast cancer, and in patients with some other health conditions.
- Overall, the decision to use HRT to alleviate symptoms and prevent potential diseases is a highly individualized one, and requires a full understanding of the patient’s health history and goals.
- Issue-specific therapies that can be considered include:
- Medications used to alleviate vasomotor symptoms include venlafaxine, pregabalin, citalopram.
- Topical methods to soothe atrophied vulvo-vaginal tissues include lubrication and moisturizers.
- To prevent of osteoporosis, we can prescribe bisphosphonates, denosumab, and other drugs, and calcium and Vitamin D supplements can be used to support bone health.
"Post-menopausal zest"
- Menopause isn’t a strictly negative experience for most women; in fact, many women enjoy the sexual freedom that comes with no longer having to worry about pregnancy, and many enjoy the relief from the cyclical changes that come with menstruation (breast tenderness, cramping, bleeding, moodiness, and headaches).
Hormonal contraceptives and Perimenopause
- Perimenopausal patients can get pregnant, so effective methods of birth control are necessary if they engage in heterosexual intercourse.
- Furthermore, hormonal contraceptives may mask and/or alleviate the symptoms of perimenopause, including hot flashes and irregular bleeding, and bone strength maintained for longer.
Male aging
- Characterized by hormonal declines and various symptoms associated with bodily changes.
- Like women, men tend to experience more sexual, psychological, and vasomotor symptoms as they age; however, the concept of a male menopause, “andropause,” is controversial.
For references, please see full tutorial.