Menopause – Causes, Symptoms, Diagnosis, Treatment

Menopause is the permanent cessation of menses for 12 months resulting from estrogen deficiency and is not associated with a pathology. The median age of menopause is 51. Most women experience vasomotor symptoms, but menopause affects many other areas of the body such as urogenital, psychogenic, and cardiovascular. This article will review hormonal and non-hormonal treatments, as well as complications of menopause. Patients are living longer, and women are spending up to one-third of their lives in post-menopause.[rx][rx][rx]

Causes of Menopause

As women grow older, their ovarian follicles diminish in number. There is a decline in granulosa cells of the ovary, which were the main producers of estradiol and inhibin. With the lack of inhibition from estrogen and inhibin on gonadotropins, follicle-stimulating hormone, (FSH) and luteinizing hormone (LH) production increases. FSH levels are usually higher than LH levels because LH is cleared from the blood faster. The decline in estrogen levels disrupts the hypothalamic-pituitary-ovarian axis. As a result, a failure of endometrial development occurs causing irregular menstrual cycles, until they stop altogether.

Menopause may occur due to surgical procedures such as a hysterectomy with bilateral oophorectomy. Menopause can be caused by treatment for certain conditions, like endometriosis and breast cancer with antiestrogens, and other cancers due to chemotherapy medications.

Symptoms of Menopause

• Vasomotor Symptoms – Approximately, 75% of women experience vasomotor symptoms. These symptoms include hot flashes, night sweats, palpitations, and migraines. Hot flashes often last approximately three to four minutes at unpredictable intervals. They may be worsened by alcohol, eating, emotional stress, and exertion. Migraines may change in intensity and severity. Migraines without aura are more common than migraines with aura. Migraines with aura have an increased risk of stroke, especially if women smoke or use oral contraceptives. Other types of headaches such as cluster and tension headaches may also increase with a change in hormone levels.
• Urogenital Symptoms – Approximately 60% of women experience urogenital symptoms. These symptoms include vaginal atrophy, urethral atrophy, and sexual dysfunction (i.e., a decline in libido).  Vaginal atrophy results in dryness, pruritus, and dyspareunia (painful intercourse). Urethral atrophy results in stress incontinence, frequency, urgency, and dysuria.
• Psychogenic Symptoms – Approximately 45% of women experience psychogenic symptoms. These symptoms include anger/irritability, anxiety/tension, depression, sleep disturbance, loss of concentration, and loss of self-esteem/confidence.
• Hot flashes and sweats: This is the most common problem in the time leading up to menopause. It can disrupt your sleep. Some women have phases where they break out in a sweat so often that it limits what they can do in everyday life. Hot flashes generally go away on their own after about 4 to 5 years.
• Changes in the membranes lining the vagina: After menopause, these membranes usually become thinner and drier.
• Urinary Incontinence – While it is defined as the persistent, involuntary loss of urine, most women would say urinary incontinence is an unfortunate, unwelcome, unwanted annoyance. Luckily, there are strategies to help improve the various forms of incontinence without medication or surgery. Try drinking adequate water to keep urine diluted (clear and pale yellow), and avoid foods or beverages with a high acid or caffeine content, which may irritate the bladder lining. These include grapefruit, oranges, tomatoes, coffee, and caffeine-containing soft drinks. Also try Kegel exercises to strengthen your pelvic floor muscles and reduce incontinence episodes.
• Night Sweats – To get relief from night sweats (hot flashes that occur during sleep), try different strategies to stay cool while you sleep:
  • Dress in light nightclothes.
  • Use layered bedding that can easily be removed during the night.
  • Or, try wicking materials for both.
  • Cool down with an electric fan.
  • Sip cool water throughout the night.
  • Keep a frozen cold pack under your pillow and turn over the pillow often so that your head is always resting on a cool surface, or put a cold pack on your feet.

  4. Trouble Falling Asleep

  Establish a regular sleep schedule and sleep routine:

  • Wake up and go to bed at consistent times, even on weekends.
  • Relax and wind down before sleep by reading a book, listening to music, or taking a leisurely bath.
  • Milk and peanuts contain tryptophan, which helps the body relax.
  • A cup of chamomile tea may also do the trick.
  • Keep bedroom light, noise, and temperature at a comfortable level — dark, quiet, and cool are conditions that support sleep.
  • Use the bedroom only for sleep and sex.
  • Avoid caffeine and alcohol late in the day.

  5. Sexual Discomfort

  Menopause contributes to sexual function changes through the decreases in ovarian hormone production and may lead to vaginal dryness and a decline in sexual function. To counteract these changes, try:

  • Vaginal lubricants: Available without a prescription, these products decrease friction and ease intercourse when the vagina is dry. Only water-soluble products should be used because oil-based products such as vaseline may actually increase irritation. Only products designed for the vagina should be used; avoid hand creams and lotions containing alcohol and perfumes as well as warming/tingling and flavored lubricants which may irritate tender tissue. (Examples of available vaginal lubricants include Astroglide, Moist Again, and Silk-E.)
  • Vaginal moisturizers: Also available without a prescription, these products improve or maintain vaginal moisture in women with mild vaginal atrophy (when tissues of the vulva and the lining of the vagina become thin, dry, less elastic, and less lubricated as a result of estrogen loss). They also help keep vaginal pH low, which ensures a healthy vaginal environment. (Examples include Replens and K-Y Long-lasting Vaginal Moisturizer.) These products can be used on a regular basis and offer a more lasting effect than vaginal lubricants.
  • Regular sexual stimulation: Last but certainly not least, women can maintain vaginal health through regular painless sexual activity, which promotes blood flow to the genital area.
• The hormonal changes can also lead to trouble falling asleep and staying asleep, mood swings or a low mood. Some women become less interested in sex. Many gain weight in this phase of their life.The lining of the vagina changes around menopause too. It usually becomes thinner and drier.

Common symptoms include:

• hot flushes – short, sudden feelings of heat, usually in the face, neck and chest, which can make your skin red and sweaty
• night sweats – hot flushes that occur at night
• difficulty sleeping – this may make you feel tired and irritable during the day
• a reduced sex drive (libido)
• problems with memory and concentration
• vaginal dryness and pain, itching or discomfort during sex
• headaches
• mood changes, such as low mood or anxiety
• palpitations – heartbeats that suddenly become more noticeable
• joint stiffness, aches and pains
• reduced muscle mass
• recurrent urinary tract infections (UTIs)

The menopause can also increase your risk of developing certain other problems, such as weak bones (osteoporosis).

• During menopause, approximately 85 percent of women report experiencing symptoms of varying type and severity.⁷ Types of symptoms experienced include the following.⁵
  • Vasomotor symptoms are recurrent, transient episodes of flushing, with intense heat on the face and upper body, sometimes followed by chills. These symptoms can occur while sleeping and can produce intense perspiration (night sweats). Individual hot flushes may last from one to five minutes. After irregular menses, vasomotor symptoms are the second most frequently reported perimenopausal symptom.
  • Increases in sleep disturbances such as insomnia and sleep apnea/hypopnea may occur. Insomnia includes lengthy times to fall asleep, inability to sleep through the night, or inability to resume sleeping when woken prematurely. Sleep apnea symptoms range from slight airflow reductions that cause snoring, to periodic cessation of breathing (apnea).
  • Psychological symptoms such as depressive symptoms, anxiety, and mood disturbances may also occur in perimenopausal and postmenopausal women. The term “depression” may include a depressed mood or an intense adjustment reaction to a life event that may not require treatment. The term may also include clinical depression. If clinical depression is suspected, assessment and treatment are recommended. Symptoms of anxiety may include tension, nervousness, panic, and worry.
  • Urogenital problems such as urinary incontinence and vaginal atrophy may occur. Vaginal atrophy describes vaginal walls that are thin, pale, dry, and sometimes inflamed. These changes cause discomfort and potential trauma during intercourse and during pelvic examinations.
  • Sexual function effects such as dyspareunia (pain during intercourse) and decreased libido are also reported by perimenopausal and postmenopausal women.

Diagnosis of Menopause

During menopause, histopathology is focused on the ovaries, urogenital, bones, and arteries.

Ovaries – In menopause, follicles age and the 2 structures of the ovaries (cortex and medulla) change. The cortex becomes thinner, such that the distinction between the cortex and medulla is less evident.  The cortex also has fewer follicles, and there is a tendency towards the fragmentation of the corpora arenacea. Additionally, there are invaginations of the surface epithelium of the cortex, and epithelial inclusion cysts are present. The medulla develops stromal fibrosis and scars. The medulla also undergoes the hyalinization of vessel walls, with architectural changes of vessels.

Urogenital – There is also a significant change in the vagina during menopause. The vagina has several epithelial layers: mucosa (most superficial), muscularis, and the adventitia (deepest). The mucosa layer of the vagina begins to atrophy due to decreased estrogen that causes this cell layer to become drier and thinner. As a result, the vaginal mucosa loses its elasticity and becomes fragile.

Bone – Healthy normal bone is constantly remodeling via a 5-step process, which involves resorption (via osteoclasts) and production (via osteoblasts). During menopause, estrogen deficiency increases osteoclastic activity, such that there is an imbalance of osteoclastic and osteoblastic activity. This results in more bone being reabsorbed and overall bone loss.  Estrogen deficiency leads the release of cytokines among them RANKK ligand (RANKL), which plays a critical role on the osteoclastogenesis cascade.

Arteries – An artery consists of 3 layers, the tunica intima (surrounding the lumen), tunica media, and tunica adventitia. Estrogen is believed to have a positive effect on the tunica intima of the artery wall, helping to keep blood vessels flexible. During menopause, estrogen deficiency causes vasoconstriction of the vessel wall and an accelerated increase of low-density lipoprotein (LDL). Thus, menopause is linked to the increased risk of cardiovascular disease, which can be denoted by increased intima-media thickness.

History and Physical

The history will include symptoms related to estrogen deficiency. The obvious symptom is the cessation of menses typically heralded by changes in the menstrual cycle.

Physical Examination

Should include measurement of blood pressure, weight and height, breast palpation, vaginal examination, and Pap smear.

• Blood Pressure: Elevated blood pressure may be noted resulting from arterial vasoconstriction.
• Weight and Height: Weight gain may be noted, as many women report some degree of weight gain during menopause. The North American Menopause Society stated women gained an average of five pounds over the menopause transitional period. Additionally, a decrease in height may be noted, associated with osteoporosis and spine fractures.
• Breast and vagina: Breast palpation usually notes decreased breast size. The vaginal examination notes dryness and urogenital atrophy. Abnormal uterine bleeding is an indication to perform a pap smear.

Evaluation

Generally, no laboratory tests are required for diagnosis menopause. The diagnosis is clinically based on the patient’s age, symptoms, and ruling out other conditions for patients older than 45 years old. Furthermore, symptoms may precede changes in laboratory values. However, an elevated serum FSH (greater than 40 mIU/mL) can be indicative of menopause (via ovarian failure), although it is insensitive. Additionally, drugs like estrogens, androgens, and hormonal contraceptives may alter lab results.

The United States Preventive Services Tasks Force suggests starting screening for osteoporosis at age 65 if normal risk factors are present. If osteoporosis is a concern (i.e., falls, fractures, medications), dual-energy x-ray absorptiometry (DEXA) scan can be done. A T-score on DEXA of 1.0 to 2.5 is indicative of osteopenia, while a T-score greater than 2.5 is indicative of osteoporosis.

Treatment of Menopause

Menopause treatment and management revolve around minimizing disruptive symptoms and preventing long-term complications.[rx][rx][rx][rx]

Treatments of interest include:

• Hormone therapies
  • Oral estrogen alone or combined with progestogen (or androgen)
  • Transdermal estrogen or combined with progestogen
  • Vaginal estrogen
  • Combined estrogen-progestogen and progesterone-only contraceptives (for women desiring contraception)
  • Compounded menopausal hormone therapy

Evidence evaluating hormone therapies will be considered separately for women with and without a uterus. Women with breast cancer will be excluded.

• Nonhormone therapies
  • Prescription
    • SSRI/SNRIs
    • Eszopiclone
    • Clonidine
    • Methyldopa
    • Gabapentin
  • Nonprescription, complementary and alternative therapies
    • Isoflavones, including red clover (Trifolium pratense)
    • Black cohosh (Cimicifuga racemosa)
    • St. John’s wort (Hypericum perforatum)
    • Ginseng
    • Flax seed
    • Vitamin E
    • Dong quai (Angelica sinensis)
    • Dehydroepiandrosterone

Nonprescription Remedies

Complementary and alternative treatments include phytoestrogens, vitamin E, and omega-3 fatty acids. Vitamin E and omega-3 fatty acids have been used to treat the vasomotor symptoms of menopause. They are generally safe; however, studies have shown that they are no better than placebo. Phytoestrogens like soy, red clover, and black cohosh have also been safely used to treat menopause symptoms. Though studies on black cohosh have shown mixed results when treating hot flashes, soy and red clover have been shown to be effective in treating osteoporosis and high cholesterol.

References

1. https://www.ncbi.nlm.nih.gov/books/NBK507826/
2. https://www.ncbi.nlm.nih.gov/books/NBK279311/
3. https://www.ncbi.nlm.nih.gov/books/NBK285446/
4. https://www.ncbi.nlm.nih.gov/books/NBK279131/
5. https://www.ncbi.nlm.nih.gov/books/NBK285446/
6. https://www.ncbi.nlm.nih.gov/books/NBK552590/
7. https://www.ncbi.nlm.nih.gov/books/NBK11956/
8. https://www.ncbi.nlm.nih.gov/books/NBK285468/
9. https://www.ncbi.nlm.nih.gov/books/NBK279309/
10. https://www.ncbi.nlm.nih.gov/books/NBK285463/