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Menopause is the time in a woman’s life when the ovaries stop producing eggs (ovulating), menstrual periods end, and the ovaries no longer make significant amounts of estrogen. Menopause does not happen suddenly. Most women experience several years of changes in their menstrual periods before they stop completely. This transition period is called perimenopause. During perimenopause, many women start to have symptoms caused by declining estrogen levels in the body. Perimenopause typically lasts between 1-3 years.

A woman has completed menopause once she has gone a full year without having a menstrual period.

When does menopause usually happen?

The median age of the onset of perimenopause is 47, and the median age of menopause is 51. Menopause happening between ages 40 – 45 is called “early menopause”, and menopause before age 40 is called “primary ovarian insufficiency”.

 

Besides menstrual cycle changes, what other signs and symptoms can occur during perimenopause?

Symptomcomments
Hot flashesA sudden sensation of heat centered on the upper chest and face that quickly radiates throughout the body. The sensation of heat lasts from 1 to 5 minutes. It is often associated with profuse sweating. It can sometimes be associated with palpitations (a rapid, strong, or irregular heartbeat). They are sometimes followed by chills, shivering, and a feeling of anxiety. This is the most common symptom of perimenopause, affecting 80% of women.
Depression and/or anxiety[1],[2],[3]Depressed mood or increased anxiety are reported to be more common during menopausal transition, though this is not a universally-accepted to be a result of menopause.
Difficulty sleepingThis can happen due to hot flashes, or even in the absence of hot flashes.
Vaginal drynessAs estrogen levels decrease, the lining of the vagina may become thinner, dryer, and less elastic. Vaginal dryness may cause pain during sex. Vaginal infections also may occur more often.
Urinary discomfortDecreasing estrogen levels leads to atrophy (shrinking) of the tissues around the urethra. The urethra can become dry, inflamed, or irritated. This can cause more frequent urination and increase the risk of urinary tract infections.
Changes in cognition (thinking)This can be reflected by forgetfulness, difficulties with finding words, and “brain fog”
Joint aches, pains, and stiffness 
Breast pain 
Menstrual migrainesMenstrual migraines are migraine headaches that cluster around the onset of each menstrual period. In many women, these headaches worsen in frequency and intensity during perimenopause.

 

How long do symptoms of menopause last?

One large study[4] found that the median duration of symptoms is 7.4 years, with variation according to race or ethnic group — 5 years among Asian women, 7 years among white women, 9 years among Hispanic women, and 10 years among black women.

 

 

What are the long term consequences of estrogen deficiency?

Bone lossBone loss begins during the menopausal transition due to low estrogen, and is most rapid during the first few years of this transition. It has been estimated that on average, women lose about 10% of their bone mass during the first 10 years of menopause[5].
Cardiovascular diseaseThe risk of cardiovascular disease increases after menopause, at least in part due to estrogen deficiency.
OsteoarthritisThere is limited data that suggest that menopause may contribute to osteoarthritis (joint pains caused by breakdown of the tissues that cushion joints)
Body compositionMenopause is associated with increased fat storage and loss of muscle mass.
Skin changesMenopause is associated with loss of collagen in the skin, which may be associated with thinning of the skin and increased wrinkling.
BalanceMenopause is associated with worsening balance.

 

I think I may be in perimenopause. Do I need lab testing?

If you have irregular periods and symptoms of menopause, it is possible that you could be perimenopausal (this is less likely if you are younger, but still possible). Make an appointment with your doctor to discuss. If based off your symptoms your doctor suspects you may be perimenopausal, they may check labs tests to evaluate for this as well as other causes of irregular periods.

  • HCG- this is a pregnancy test, which is sometimes checked if it is possible you could be pregnant.
  • TSH- a measurement of thyroid function. Abnormal thyroid function can cause irregular periods.
  • Prolactin- a hormone that stimulates breast milk production, which can sometimes become elevated outside of pregnancy and cause irregular periods
  • FSH- a hormone that is important in the stimulating ovaries to develop eggs and ovulate. This hormone level rises during perimenopause, so can sometimes be used to provide evidence of perimenopause.
  • Estradiol

 

What hormones can used to treat menopause? 

  • Estrogen: This is the gold standard for relieving the symptoms associated with menopauseThe Endocrine Society recommends the use of estrogen patches rather than pills because this method of delivering estrogen most closely mimics how the body would produce estrogen, and it appears to have the lowest associated risks.

 

  • Progesterone: Progesterone replacement is mandatory for women on estrogen who still have a uterus, in order to prevent endometrial cancerOn the other hand, for women who do not have a uterus, taking progesterone does not provide any additional benefits than estrogen alone.

 

Is there a role for testosterone replacement to treat symptoms of menopause?

  • Testosterone: In men, low testosterone is associated with decreased sex drive, and testosterone therapy in men is proven to increase sex drive. However, the situation is more complex women. Low testosterone levels in women are not necessarily associated with low sex drive, lab assays are often inaccurate in measuring testosterone in women, and there is limited evidence in women that replacing testosterone is safe or effective. The Endocrine Society, American College of Obstetrics and Gynecology, and the North American Menopause Society all recommend against routine use of testosterone in postmenopausal women with low sex drive[6][7]. However, there are instances where a short trial of testosterone therapy may be considered.

 

How is hormone therapy given?

  • Estrogen can be given in several forms. Systemic forms include pills, skin patches, and gels and sprays that are applied to the skin. With systemic therapy, estrogen is released into the bloodstream and travels to the organs and tissues where it is needed.
  • Women who only have vaginal dryness may be prescribed “local” estrogen therapy in the form of a vaginal ring, tablet, or cream. These forms release small doses of estrogen into the vaginal tissue.
  • If progestin is prescribed, it can be given separately or combined with estrogen in the same pill or in a patch.

 

What are “Bioidentical” hormones?

  • The term “bioidentical hormone” technically refers to a hormone with the same molecular structure as a hormone the body makes. For example, 17-beta estradiol is available in tablet form and is bioidentical to human 17-beta estradiol made by the ovary. However, in popular culture the term “bioidentical” refers to custom compounded hormone preparations, with adjustments based off repeated measurements of hormone levels. Compounded drugs are not regulated by the U.S. Food and Drug Administration (FDA).
  • Bioidentical hormones became popular years ago due to safety concerns over conventional hormone preparations. However, there is no evidence that custom compounded (so-called bioidential) hormones are any safer than conventional hormone therapy. Rather, they are potentially less safe and less effective because of the lack of stringent quality controls regarding purity and dosing.
  • People who prescribe bioidentical hormones often use misleading arguments for their benefits, especially the notion that bioidentical hormones are “natural” whereas other hormone preparations are “synthetic”. This is patently untrue. With the exception of conjugated equine estrogens (which are purified from the urine of pregnant horses), all bioidentical hormones are synthetic.
  • The North American Menopause Society, American College of Obstetricians & Gynecologists as well as The Endocrine Society recommend against the use of these compounded formulations because there are no large scale studies evaluating safety, effectiveness, or validity of their dosing.

 

Who should consider hormone therapy, and what are the benefits?

Women aged 45-59 with symptoms should consider hormone therapy if their symptoms are highly bothersome or reduce quality of life. In women with menopause before age 45, hormone therapy is recommended (as long as there is not a contraindication) until at least the average age of menopause.

Hormone therapy is the best treatment for the relief of hot flashes and night sweats. Both systemic and local types of estrogen relieve vaginal dryness. Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures.

What are the risks of hormone therapy?

Estrogen therapy has long been recognized as the most effective treatment for the relief of symptoms associated with menopause. However, doctors were also prescribing hormone therapy to prevent of heart disease and osteoporosis based off of epidemiologic data showing a protective effect.  There had never been a prospective randomized clinical trial (the gold standard in medical research) to prove that menopausal hormone therapy truly reduced these risks. In 2002, the Women’s Health Initiative[8](WHI) trials were completed in an attempt to answer whether hormone therapy reduced the risk of osteoporosis and heart disease in menopausal women.

WHI was a set of two hormone therapy trials (estrogen only vs placebo, combined estrogen-progesterone versus placebo) in approximately 27,000 postmenopausal women (mean age 63 years). These trials unexpectedly showed a number of adverse outcomes, including an excess risk of heart disease, stroke, blood clots, and breast cancer. Similar results were found in a meta-analysis of 22 studies[9] as well as a 2017 United States Preventive Services Task Force meta-analysis of 18 trials[10]. Based off this research, we no longer recommend using hormone therapy to reduce the risk of osteoporosis or heart disease, and limit the use of hormone therapy in women over age 60.

 

But while the WHI clearly showed the adverse effects of hormone therapy in older postmenopausal women (over age 60 years), this is not the age group that is primarily affected by menopausal symptoms. Almost all women who seek medical therapy for menopausal symptoms do so in their late 40s or 50s, and the risk of menopausal hormone therapy in this population is much lower.

 

The consensus now is that for most most healthy symptomatic women, without contraindications and closer to the time of menopause (less than 10 years after menopause onset or age less than 60) are appropriate candidates for MHT for symptom relief,[11],[12]

 

Estimates of risks and benefits of menopausal hormone therapy in women less than 60 years old[xiii]

 

Estimates of the effects of orally administered estrogen (in the form of conjugated equine estrogens) alone or combined with progesterone (in the form of medroxyprogesterone acetate) in women ages 50 to 59 years in the Women’s Health Initiative trial[xiv]. The above graph shows the estimated excess risks and benefits per 1000 women using hormone therapy for five years. It is important to note that the WHI studies did not have enough participants for age-related subset analysis, and none of the data presented in the figure are statistically significant. Nonetheless, this figure represents the best available estimates.

 

Who should NOT receive menopausal hormone replacement? 

  • Women who have had prior blood clots or stroke.
  • Women with high risk of cardiovascular disease (greater than 10% over next 10 years).
    • To estimate your cardiovascular risk, please check the American College of Cardiology’s website. You will need to know your cholesterol levels and your blood pressure to complete the calculator. https://tools.acc.org/ascvd-risk-estimator-plus
  • Women who have known breast or endometrial cancer or who have strong family histories of breast cancer.
  • Women with active liver disease.
  • Women with any new vaginal bleeding after menopause.

 

Are there natural supplements or treatments I can take to reduce menopausal symptoms?

  • In randomized clinical trials, natural supplements have failed to show benefit compared to placebo[xv],[xvi]. The most common supplements marketed to treat menopause are include phytoestrogens, black coshosh, dong quai, evening primrose oil, flaxseed maca, n-3 fatty acids, ginseng, red clover, and vitamin E.
  • Cognitive behavioral therapy has been shown to offer modest reducing distress from hot flashes.
  • Accupuncture has been shown in some trials to reduce hot flash frequency, while others have shown no effectxvi.
  • Yoga has been associated with improved mood, but no effect on hot flash severity or frequency.

 

Are there other medications besides hormones that can improve hot flashes?

  • While less effective than estrogen, there are non-hormonal medications that can improve menopausal symptoms (particularly hot flashes). These include SSRIs (paroxetine, escitalopram, citalopram, fluoxetine), SNRIs (venlafaxine, desvenlafaxine), gabapentinoids (pregabalin, gabapentin). If you are potentially interested, talk with your doctor about these options.

 

Additional Resources:

 

 

 

[1] Mishra GD, Kuh D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ 2012

[2] Liu M, et al. A health survey of Beijing middle-aged registered nurses during menopause. Maturitas. 2013

[3] Freeman EW, et al. Temporal associations of hot flashes and depression in the transition to menopause. Menopause 2009.

[4] Avis NE, et al. Duration of menopausal vasomotor symptoms over the menopause transition.JAMA Intern Med 2015

[5] Greendale GA, et al. Bone mineral density loss in relation to the final menstrual period in a multiethnic cohort: results from the Study of Women’s Health Across the Nation (SWAN). J bone miner res 2012.

[6] Elraiyah T, et al. Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. JCEM. 2014.

[7] Davis SR, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. JCEM. 2019.

[8] Writing group for the Women’s Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progesterone in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. JAMA 2002.

[9] Marjoribanks J, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2017

[10] US Preventative services task force. Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement. JAMA 2017.

[11] ACOG Practice Bulletin No. 114: management of menopausal symptoms. Obstet Gynecol. 2014.

[12] The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017.

[xiii] Stuenkel CA, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. JCEM 2015.

[xiv] RJ Santen, et al. Competency in menopause management: whither goest the internist? J Women’s Health (Larchmt) 2014

[xv] Johnson A, et al. Complementary and alternative medicine for menopause. J Evid Based Integr Med 2019

[xvi] Pinkerton JV, Santen RJ. Managing vasomotor symptoms in women after cancer. Climacteric 2019