Menopause-Basics and Clinical by Dr Shahjada Selim

1. Menopause-
Basics and Clinical
Dr Shahjada Selim
Associate Professor
Department of Endocrinology, BSMMU
Faculty in Endocrinology, Texila American University, USA
Website: shahjadaselim.com

2. Menopause Basics
Learning Objectives:
• Describe the hypothalamic-pituitary-ovarian axis
• Differentiate between Perimenopause and Menopause
• Learn physiologic and anatomic changes at menopause
• Describe typical menopausal symptoms
• Perform focused history +physical for menopausal woman
• Interpret selected laboratory tests to evaluate menopause.
• Counsel patients regarding female sexuality and aging
– physical, emotional, and relationship-based issues

3. What does menopause mean to women?
• Cessation of menstrual periods
• End of reproductive capacity
• Hormonal changes
• Change of life, a life stage
• End of prior symptoms
• Beginning of new symptoms
• Changing emotions
• Changing body
• Aging process
• Disease risks
• Medical care needs
Woods et al. Menopause 1999.

4. Menopause: The Reality
• Clinical diagnosis
• Permanent cessation of menses
following the loss of ovarian activity
• Lack of menses for 12 months
• Mean age in US is 51 (45-55 years)
• Women will spend one-third to one-half
of their lives postmenopausally
Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive

5. “The anchor point that is defined after
12 months of amenorrhea following the
final menstrual period (FMP), which
reflects a near complete but
natural diminution of ovarian hormone
secretion.”
Soules et al. Menopause 2001.
Menopause

6. “Occurs after 12 consecutive
months of amenorrhea, for which
there is no other obvious pathologic
or physiologic cause.”
(Average age in Western world is 51 years)
Natural (spontaneous) menopause
Utian. Climacteric 1999.

7. Premature menopause
“Menopause that occurs in
women at or under40 years old.”
Utian. Climacteric 1999.

8. Premature ovarian failure
• Hypergonadotropic
amenorrhea ≥ 40 years old
• Associated with many
other health conditions
(eg, autoimmune, toxic, genetic)
• May not be permanent
• Is not the same as
premature menopause

9. Premature ovarian failure
(continued)
• Ovarian insufficiency leading to
amenorrhea that occurs in women ≥ 40
• Can be transient (eg, from over-
exercising, eating disorders, high
stress levels
• Can be permanent (eg, from
autoimmune disease or genetic
abnormalities) and equivalent to
premature menopause

11. STRAW reproductive aging system
Length
decreases
-2 days
Stages of Reproductive Aging Workshop. Menopause 2001.

14. Ahuja M. Age of menopause and determinants of menopause age: A PAN India survey by IMS. J Mid-life Health 2016;7:126-
31
Average age of menopause of an Indian woman is 46.2 years
much less than their Western counter parts (51 years). A definite
rural and urban division was also seen. There was a correlation
between the age of menopause and social and economic status,
married status, and parity status.
Age of menopause and determinants of
menopause age: A PAN India survey by IMS

15. “Symptoms” of perimenopause
• Natural, normal changes, not a disease
• Subtle hormonal changes during the 30s
• Symptoms noticeable during the 40s
• Disturbances may be acute or gradual
• Not all midlife symptoms are attributable
to menopause

16. Induced menopause
“Cessation of menstruation that follows
bilateral oophorectomy (surgical
menopause), iatrogenic ablation of
ovarian function by chemotherapy
or pelvic radiation therapy.”
(No perimenopause transition for
these women)
Utian. Climacteric 1999.

17. Premature or induced
menopause: complicating factors
• Early loss of fertility
• More severe symptoms
• Greater risk of osteoporosis and CVD
• Possibly complicated by sequelae of
underlying disease
• Little research regarding benefits/risks
of treatment

18. Hypothalamic-pituitary-ovarian axis
Pituitary HypothalamusGnRH (+)
Estradiol
Progesterone
LH FSH Inhibins
Ovary

19. Reproductive aging
• 1-2 million follicles at birth, only
approximately 1,000 by menopause
• Most follicular loss due to atresia,
not ovulation
• Atresia accelerates at around age 37
• Age-related uterine changes also
contribute to decreased fertility

20. Ovarian function
in perimenopause
• Ovaries begin decreasing in size
• Estradiol still dominant estrogen
• Number of follicles decreases substantially
• Production of inhibin decreases
• Remaining follicles respond poorly
to elevated FSH and LH
• Erratic ovulation results in menstrual
cycle irregularity

21. Decline in fertility
• Fertility wanes starting at about age 37,
before perimenopause signs occur
• By age 45, risk of spontaneous
miscarriage increases to 50%
• Fertility-enhancing techniques available
• Natural pregnancy still possible until
menopause is reached

22. Physiology: perimenopause
• Estrogen and progesterone levels
fluctuate erratically
• Very high serum estrogen levels
may result
• Gradual decline in testosterone with
age beginning mid-30s
Zumoff et al. J Clin Endocrinol Metab 1995.
Burger et al. J Clin Endocrinol Metab 2000.

23. Serum hormone levels
at menopause
Circulating estrogens
Ratio of estrogen to androgen
Sex hormone-binding globulin secretion
Peripheral aromatization of DHEA
to estrone
Reversal of E2 to E1 ratio
No significant change in
testosterone levels
•

24. Burger et al. J Clin Endocrinol Metab 1999.
E, FSH, and inihibins prior and following FMP

25. Health evaluation
at perimenopause
• Determine the primary complaint(s)
• Medical, psychological, and social history
• Family history
• Complete physical examination
• Determine quality of life
• Laboratory tests
– For differential diagnosis of problems
– Screening tests for specific chronic conditions

26. Routine screens
• Standard blood screens
• Periodic serum cholesterol (total, HDL, LDL, TG)
• Fasting glucose
• Thyroid screen
• Annual Pap test
• Periodic stool guaiac test, sigmoidoscopy,
colonoscopy
• Annual mammogram
• Urine screen, when indicated
• Sexually transmitted infections, when indicated
• Bone density, when needed

27. 0
10
20
30
40
50
60
70
80
90
100
Less
than 15
15-19 20-24 25-29 30-34 35-39 40 and
older
Unintended Pregnancies Unintended Pregnancies Ending in Abortion
Proportion of All U.S. Unintended
Pregnancies by Age: 1994
Percent
Age (years)
Evaluate need for contraception
Proportion of all US unintended pregnancies by age: 1994
Unintended pregnancies Unintended pregnancies ending in abortion
Henshaw. Fam Plann Perspect 1998.

28. Confirming menopause
• Age, medical/menstrual history, and
symptoms usually sufficient
• Rule out other causes of symptoms
(eg, thyroid disorder)
• Consistently elevated FSH (> 30 mIU/mL)
diagnostic, but rarely necessary except
with nonsurgically induced menopause
• Serum estradiol testing may be of value;
value of salivary levels unproven

29. Evaluate risk for specific
conditions and diseases
• Vasomotor symptoms/sleep disturbance
• Vulvovaginal health
• Psychological health
• Cardiovascular disease
• Diabetes
• Osteoporosis
• Cancer
• Sexual function
• Sexually transmitted infections
• Urinary incontinence
• Alcohol/drug use/abuse
• Domestic abuse/violence risk

30. Assess all women for
alterable risk factors
• Smoking
• Poor diet
• Obesity
• Lack of exercise
• Stress
• Habit-forming drugs
• Unsafe sex
• Excess alcohol
• No seat belts

31. Therapeutic options
• No intervention/treatment
• Lifestyle modification
• Nonprescription remedies
• Complementary and alternative
medicine (CAM) approaches
• Prescription drugs
• Surgical procedures

32. Write a lifestyle Rx
• Stop smoking
• Have a nutritionally sound diet
• Achieve and maintain healthy weight
• Reduce stress
• Avoid excess alcohol
• Say no to drugs and unsafe sex
• Wear seat belts
• Exercise regularly

33. Benefits of regular exercise
• Decreases hot flashes
• Improves mood and sleep
• Decreases/maintains weight
• Supports joint/muscle flexibility
• Prevents bone loss
• Decreases risk of many
other diseases

34. “Improved control of behavioral risk
factors, such as use of tobacco, alcohol,
and other drugs, lack of exercise, and
poor nutrition, could prevent half of
premature deaths, one-third of all cases
of acute disability, and all cases of
chronic disability.”
US Preventive Services Task Force. Guide to Clinical Preventive Service 1989.

35. Vasomotor symptoms
• One of the hallmarks of perimenopause
• Includes hot flashes and night sweats
• Recurrent, transient episodes of flushing,
perspiration, and intense warmth on upper
body and face
• Skin temperature increases 1-7 ºC,
returns to normal gradually
• Chill often follows

36. Causes of hot flashes
• Precise cause is unknown
• Estrogen levels alone not predictive
of hot flash frequency or severity
• Other conditions: thyroid disease,
epilepsy, infection, insulinoma,
carcinoid syndromes, leukemia,
pancreatic tumors, autoimmune
disorders, mast-cell disorders

37. 37
0
5
10
15
20
25
30
35
40
45
50
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 28 29 30 32 36 38 41 44
Years
NumberofSubjects
Number of years women report having
hot flushes as estimated by a survey of 501
untreated women who experienced hot flushes
Hot Flushes May Continue
Years After Menopause
Ages 29 to 82 Years
Mean age of natural menopause was 49.5 years; mean age of surgical menopause was 43.7 years.
Kronenberg F. Ann NY Acad Sci. 1990;592:52-86. Used with permission.

38. Causes of hot flashes
(continued)
• Drugs: tamoxifen, raloxifene
• Lifestyle factors: warm ambient air
temperature, higher BMI, cigarette
smoking, less physical activity

39. Hot Flashes: Demographics,
Lifestyle, Health
• Symptoms vary by race/ethnicity
– More African Americans and Hispanics than
Caucasians affected
– Fewer Chinese than Caucasian affected
• Significant association with
– BMI
– Passive smoke exposure
– History of premenstrual symptoms
– Use of OTC pain medication
– History of comorbidities
– Perceived stress
– Age
Gold EB et al. Am J Epidemiol. 2004;159(12):1189-1199

40. Alternative Approaches for Vasomotor
Symptoms: Lifestyle Adaptations
Guidelines from NAMS
– Limited effectiveness
• Cooling body core temperature
• Exercise
• Paced respirations (catecholamine control)
• Relaxing activities
– yoga, massage, meditation, paced respiration,
leisurely bath
• Avoid Triggers
– spicy food, hot drinks, caffeine, alcohol
NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms) Menopause. 2004;11:11-33;
Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813
Huntley AL, Ernst E. Menopause. 2003;10:465-76.

41. Non-Prescription Remedies
Side effects and drug interactions clearly
occur
Lack long-term safety and efficacy data
– Phytoestrogens/isoflavones
• Dietary or supplements (soy-derived)
• Red clover
– Black cohosh
– Vitamin E - not clinically significant
– Studies show no effect compared with placebo
• Dong quai
• Ginseng
• Evening primrose oil
NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms). Menopause. 2004;11:11-33;
Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813; Huntley AL, Ernst E. Menopause. 2003;10:465-76.

42. Clinical Management
Mild Vasomotor Symptoms
– For mild vasomotor symptoms
• Encourage lifestyle changes
• Non-prescription remedies- tested short term with
little efficacy over placebo but no evidence of harm
– Dietary isoflavones
– Black cohosh
– Vitamin E

43. Clinical Management
Mod-Severe Vasomotor Symptoms
• Hormone therapy is only FDA approved
treatment
– “gold standard”
• SSRI’s and gabapentin
–have efficacy in early studies
• Progestogens effective
– however large doses required
• Clonidine (oral or transdermal)

44. Lifestyle Issues in Menopause
• Vasomotor (hot flushes and night sweats)
• Low libido/painful intercourse
• Weight gain
• Memory problems, difficulty concentrating
• Mood swings
• Insomnia, fatigue
• Dizziness, rapid irregular heartbeat
• Atrophic vaginitis, bladder irritability
• Headaches
Rapkin AJ. Am J Obstet Gynecol. 2007;196(2):97-106.

45. OCs:
noncontraceptive benefits
• Suppress vasomotor symptoms
• Restore predictable menses
• Decrease dysmenorrhea
• Enhance BMD
• Prevent endometrial and
ovarian malignancies

46. OCs: when to stop
• FSH testing not reliable in
perimenopausal women or in those
using OCs
• If contraception needed, continuation
to mid-50s reasonable
• Otherwise, consider stopping early 50s
• Low-dose OC has more hormone
than EPT

47. Depression or Menopause?
Depressed1,2
Weight change1
Energy2
Sleep2
Libido1
Thoughts
of death1,2
Worthlessness1,2
Concentration2
Anhedonia1,2
Hot flushes1
Perspiration1
Vaginal dryness1
1. Soares CN, Cohen LS. CNS Spectrums. 2001;6:167-174.
2. Joffe H et al. Psychiatr Clin North Am. 2003;26:563-580.
Irritable1,2
Depression Menopause

48. Sleep disturbances
• 1/3 - 1/2 of US women aged 40-54 report
sleep problems
• Occur mainly in women with nighttime hot flashes
• Most adults require 6-9 hr sleep nightly
• Potential causes: ovarian hormone changes,
advancing age, onset of sleep disorders
(eg, apnea), stress, painful chronic illnesses
(eg, arthritis), other conditions (eg, CVD, allergies),
drugs (eg, thyroid medication)
• Insomnia produces fatigue, irritability, chronic
illness (eg, CVD), mood disorders (eg, depression)

49. Improve sleep hygiene
• Lower light and noise
• Adjust temperature (cool preferred)
• Avoid heavy evening meals
• Avoid alcohol, caffeine, nicotine
throughout the entire day
• Exercise daily, but not close to bedtime
• Use bedroom only for sleep and
sexual activities
• Have a regular sleep schedule, even
on weekends
• Use relaxation techniques

50. 3Erlik et al. JAMA 1981.
4Polo-Kantola et al. Am J Obstet Gynecol 1998.
5Antonijevic et al. Am J Obstet Gynecol 2000.
ET effects on sleep
• Decreases frequency of
− Night sweats1-4
− Periods of wakefulness during the night 3,4
• Reduces sleep latency 1,2
• Improves sleep in menopausal women with
insomnia, even in the absence of vasomotor
symptoms4
• Increases the percentage of REM sleep 2,5
• For EPT, use bedtime dosage of progesterone, a
mild soporific, to improve sleep
1Scharf et al. Clin Ther 1997.
2Schiff et al. Maturitas 1980.

51. Uterine bleeding changes
during perimenopause
• Strong predictor of perimenopause
• About 90% of women have 4-8 years of cycle
changes before reaching menopause
• No universal definition of “irregular” but unique
to each woman
• Possible changes:
– lighter bleeding (avg blood loss, < 20ml)
– heavier bleeding (avg blood loss, > 40ml)
– bleeding lasting for < 2 days or > 4 days
– cycle length < 7 days or > 28 days
– skipped periods

52. Bleeding during
postmenopause
• Must be assessed
• Vaginal causes
• Uterine fibroids
• Endometrial or endocervical polyps
• Uterine or cervical malignancy
• EPT

53. Diagnostic workup for AUB
• Comprehensive history and
pelvic exam
• Blood tests
• Endometrial biopsy
• Vaginal ultrasound
• Additional tests, such as
sonohysterogram or hysteroscopy

54. Dryness
Itching
Burning
Dyspareunia
Symptoms
Presenting genital symptoms and
physical signs of vaginal atrophy
Bachmann et al. Am Fam Physician 2000.
Pale, smooth, or shiny vaginal epithelium
Loss of elasticity or turgor of skin
Sparsity of pubic hair
Dryness of labia
Fusion of labia minora
Introital stenosis
Friable, unrugated epithelium
Signs on physical exam
Pelvic organ prolapse
Rectocele
Vulvar dermatoses
Vulvar lesions
Vulvar patch erythema
Petechiae of epithelium
Burning leukorrhea
Vulvar pruritus
Feeling of pressure
Yellow malodorous discharge

55. 1Oriba HA, Maibach HI. Acta Derm Venereol. 1989;69:461-5.
2Bachmann GA, et al. In: Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. 2nd ed. 1999:195-201.
Physiology of Vulvovaginal
Changes: Structure and
Histology
– Loss of collagen and
adiposity in vulva1
– Clitoral glans loses
protective covering2
– Vaginal surface thinner,
less elastic; more friable2

56. Non-Rx therapies
for vaginal dryness
• Vaginal moisturizers effective; also produce
low pH to guard against infection
• Vaginal lubricants ease penetration
• Avoid use of petroleum-based products
• Douches may worsen condition;
antihistamines may have drying effect
• Continued sexual activity and/or
stimulation may benefit vaginal health

57. ET and vulvovaginal atrophy
• Local estrogen appears at least
as effective as systemic ET
• If genital atrophy present without
vasomotor symptoms, nonsystemic
therapy preferred
• Stimulation of endometrium
observed with high doses, some
advise adding progestogen1
1NAMS Position Statement. Menopause 2004.

58. Improvement in vaginal
cytology with local CEE
Baseline Cycle 1
Raymundo et al. International Federation of Gynecology and Obstetrics 2000.
Open-label, single-treatment group, outpatient study
N = 105 women with data valid for efficacy analysis
Treatment significantly increased superficial and intermediary cells
and decreased parabasal cells (P < .05)

59. Sexual
excitement
and tension
Desire
Time
Reduction
Arousal
Plateau
Orgasm
Traditional sex response cycle
Kaplan. The New Sex Therapy: Active Treatment of Sexual Dysfunctions 1974.

60. Sexual Response: Male vs Female

62. Female sexual dysfunction:
definition and classification
International Consensus Development Conference on Female Sexual Dysfunction
Basson et al. J Urol 2000.
I. Sexual desire disorders
– hypoactive sexual desire disorder
– sexual aversion disorder
II. Sexual arousal disorder
III. Orgasmic disorder
IV. Sexual pain disorders
– dyspareunia
– vaginismus
– noncoital sexual pain disorder

63. Female sexual dysfunction
• Affects 20% to 50% of women1
• Multidimensional and multicausal
combining biological, psychological,
and interpersonal factors1
• Physically and emotionally distressing,
and socially disruptive1
• Increases with age2
• Must cause distress to be a dysfunction
1Basson et al. J Urol 2000.
2Goldstein. Int J Impot Res 2000.

64. Effect of perimenopause on
parameters of sexual functioning
Cross-sectional data reported from longitudinal, population-based
Australian cohort, 45-55 yrs
↓ Sexual responsivity
↓ Sexual frequency
↓ Libido
↑ Vaginal dyspareunia
↑ Partner problems
Dennerstein et al. Obstet Gynecol 2000.

65. 46
51
46
23
20
30
0 20 40 60 80 100
Very
Concerned
Somewhat
Concerned
*Numbers do not add up because of rounding; n = 500.
Bennett, Petts & Blumenthal. National Survey of American Adults 25 and Older. Washington, DC: March 1999.
Marwick C. JAMA. 1999:281:2173-4. Used with permission.
If You Wanted to Talk to Your Doctor About a Sexual Problem,
How Concerned Would You Be About the Following?
76
71
68*
Physician-Patient Communications Concerning
Sexual Problems May Not Be Optimal
There Would Be No Medical
Treatment for Your Problem
Your Doctor Would Dismiss
Your Concerns and Say
It Was All Just in Your Head
Your Doctor Would Be
Uncomfortable Talking About
the Problem Because It Was
Sexual in Nature
Percentage

66. Sexual history sample questions
• “Are you sexually active?”
• “Are you having any sexual difficulties
or problems at this time?”
• “Have you noted any change in your
sexual interest?”
• “Are you having any difficulty with
vaginal lubrication?”
• “Do you have any concerns about
your sexual health?”
Bachmann et al. Obstet Gynecol 1989.

67. 67
Model of complete clinical
care
Engage
Empathize
Educate
Enlist
Fix It
Find It
Opening
Closing
Communication
Tasks
Biomedical
Tasks

68. Criteria for Informed
Decision Making
1. Discussion of patient’s role in decision
making
2. Discussion of clinical issue or nature of
decision
3. Discussion of alternatives
4. Discussion of the pros and cons of
alternatives
5. Discussion of uncertainties of decision
6. Assessment of patient understanding
7. Exploration of patient preference