PERIMENOPAUSE

DIAGNOSE AND MANAGEMENT

Yuanita Asri Langi

Endocrinology and Metabolic Division, Internal Medicine
Department, Faculty of Medicine , University of Sam
Ratulangi/ Prof.R.D. Kandou Hospital, MANADO
 Physiology of
hypothalamus-hypophysis-ovaries axis
 https://menstrual-cycle-
calculator.com/reproductive-processes-
precede-menstruation/
http://archive.cnx.org/cont
ents/8628a146-64f6-4c08-
8b6a-
d5ccfedfd74d@3/human-
biology-chapter-14-3-
female-reproductive-
anatomy-and-physiology-
gestation-and-labor
 Pre-ovulatory follicle is
responsible for production
of 17β-estradiol

Ovarian follicular development

©2016 by American Physiological Society
Modified from : H. L. Brooks et al. Physiology 2016;31:250-257
SANDRA J. RICHARDSON. J Clin Endocrinol Metab 65: 1231, 1987
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Perimenopause : definition
Definition
• Menopause : diagnosed retrospectively after cessation of menses for 12
months in a previously cycling woman.

• Perimenopause : an interval preceding the menopause characterized by

variations in menstrual cycle length and bleeding pattern, mood
shifts, vasomotor, and vaginal symptoms and with rising FSH levels
and falling anti-Mullerian hormone and inhibin B levels, which starts
during the late reproductive stage and progresses during the menopause
transition.
Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
The Stages of Reproductive Aging Workshop + 10 staging system for reproductive aging in women
J Clin Endocrinol Metab. 2012;97(4):1159-1168. doi:10.1210/jc.2011-3362
Implications of lower estrogen level in
perimenopause
https://classconnection.s3.ama
zonaws.com/544/flashcards/66
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 Sign and symptom
Irregular periods
As ovulation becomes more unpredictable :
 The length of time between periods may be longer or shorter
• A persistent change of > 7 days in the length of, may be in early
perimenopause.
 Flow may be light to heavy
 Skip some periods
 A space of > 60 days between periods, likely in late perimenopause.

https://www.mayoclinic.org/diseases-conditions/perimenopause/symptoms-causes/dxc-20253775
 Sign and Symptom
Hot flashes and sleep problems
 Hot flashes are common during perimenopause.
 The intensity, length and frequency vary.
 Sleep problems are often due to hot flashes or night sweats, but sometimes
becomes unpredictable even without them.
Mood changes
 Mood swings, irritability or increased risk of depression.
 May link with sleep disruption associated with hot flashes.

https://www.mayoclinic.org/diseases-conditions/perimenopause/symptoms-causes/dxc-20253775
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 Sign and symptom

Vaginal and bladder problems

Lose lubrication and elasticity of vaginal tissue, dyspareunia.
More vulnerable to urinary or vaginal infections.
Loss of tissue tone contribute to urinary incontinence.
Decreasing fertility.
But, as long as having periods, pregnancy is still possible.

https://www.mayoclinic.org/diseases-conditions/perimenopause/symptoms-causes/dxc-20253775
 Sign and Symptom
Changes in sexual function
Change of sexual arousal and desire, but satisfactory sexual intimacy
before menopause, will likely continue through perimenopause and
beyond.
Loss of bone.
Increases risk of osteoporosis .
Changing cholesterol levels.
 LDL and  HDL,  the risk of cardiovascular disease

https://www.mayoclinic.org/diseases-conditions/perimenopause/symptoms-causes/dxc-20253775
Approach to menopause guideline
From: Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline
J Clin Endocrinol Metab. 2015;100(11):3975-4011. doi:10.1210/jc.2015-2236
1.0 Diagnose
• Based on the clinical criteria of the menstrual cycle.

• If establishing a diagnosis is necessary for management in women undergone a

hysterectomy without bilateral oophorectomy or a menstrual history inadequate
to ascertain menopausal status :
• Making a presumptive diagnosis based on the presence of vasomotor
symptoms (VMS)
• When indicated, laboratory testing : replicate measures of FSH and serum
estradiol.

Modified from : Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–
4011, 2015
2.0. Health considerations during perimenopause

• Address bone health

• Smoking cessation and alcohol use

• Cardiovascular risk assessment and management

• Cancer screening and prevention

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
All postmenopausal women should be encouraged to consume a diet replete with
calcium and vitamin D
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Estrogen may play a protective
role against heart disease
because of the observed
increase in cardiovascular-
related disease and death after
age 50 years

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
3.0 Hormone therapy for menopausal symptom relief

• Identifying which late perimenopausal and recently

postmenopausal ( < 60 yrs.o , < 10 years since the onset
of menopause) women are candidates. Considerations
include the risks and benefits.

• Screen before initiating MHT for cardiovascular and breast

cancer risk.

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
 3.0 Hormone therapy for menopausal symptom relief

• Recommend the most appropriate th/ depending on risk/benefit

considerations.

• A shared decision-making approach to decide: choice of formulation,

starting dose, the route of administration of MHT, and how to tailor MHT to
each woman’s individual situation, risks, and treatment goals.

• All perimenopausal women should embrace appropriate lifestyle

measures.

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
 4.0 Nonhormonal therapies for VMS
1. Non medication : turning down the thermostat

 dressing in layers

 avoiding alcohol and spicy foods

 reducing obesity and stress

2. Non hormonal medication : (SSRIs)/serotoninnorepinephrine reuptake inhibitors

(SNRIs) or gabapentin, or pregabalin (if there are no contraindications).

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
 4.0 Nonhormonal therapies for VMS
3. Complementary medicine therapies :

• black cohosh, omega-3-fatty acids, red clover, vitamin E. (lack of consistent

evidence for benefit for botanicals)

• mind/ body alternatives including anxiety control, acupuncture, paced

breathing, and hypnosis

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
5.0 Treatment of genitourinary syndrome of
menopause
a. Vaginal moisturizers and lubricants

b. Vaginal estrogen therapies

• women without a history of hormone- (estrogen) dependent cancers

who are symptoms of genitourinary syndrome of menopause (GSM)
(including vulvovagina atrophy = VVA) persist despite using vaginal
lubricants and moisturizers.

Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100: 3975–4011, 2015
 Hormone replacement therapy

Hormonal products available may contain following ingredients:

1. Estrogen alone
2. Co,bined estrogen and progesterone
3. Selective estrogen receptor modulator (SERM)
4. Gonadomimetics, such as tibolone
( estrogen+progesterone+androgen)

Kaur K. Menopausal Hormone Replacement Therapy. Medscape Sept. 2016

 Approach to the patient with
VMS contemplating MHT

From: Treatment of Symptoms of

the Menopause: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab.
2015;100(11):3975-4011.
doi:10.1210/jc.2015-2236
 Approach to the patient with
VMS contemplating MHT

From: Treatment of Symptoms of

the Menopause: An Endocrine
Society Clinical Practice Guideline
J Clin Endocrinol Metab.
2015;100(11):3975-4011.
doi:10.1210/jc.2015-2236
 HRT and Risks of Malignancy

• WHI → breast cancer risk ↑ in those taking

combined estrogen-progesterone th/ but not
in posthysterectomy patients taking estrogen
alone. ( mean age of samples 63 years old)
• EPIC → higher baseline circulating prolactin
levels increased breast cancer risk in
postmenopausal women receiving HRT.

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 HRT and Risks of Malignancy

• Women with an intact uterus should be placed on

a progestational agent to avoid the approximately
two- to threefold increase in the endometrial
cancer risk noted when estrogen is used alone
• WHI →HRT (combined estrogen-progestin) is
associated with a 50%  of relative risk of colon
cancer.
• HRT does not ↑ the risk of ovarian cancer
significantly.
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
http://slideplayer.com/slide/5713332/18/images/19/Which+Type+of+HRT+HRT.+With+Uterus.+Without+Uterus.+Urogenital+Symptoms.+Perimenopausal.+Postmenopausaal..jpg
 Choosing of HRT regimen

The estrogen regimen should be

tailored to the individual needs and
characteristics of the patient and
should use the lowest dosage that
alleviates symptoms.

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 Choosing of HRT regimen

 Transdermal estrogen:  risk of venous

thromboembolism (VTE) and less increase in
triglyceride.
 Oral estrogen : greater  in LDL and  in HDL.
 Women with only vaginal symptoms  local
estrogen th/ with an estrogen-impregnated ring or
a low-dose vaginal tablet.

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 Choosing of HRT regimen

 Symptoms and possible side effects should

be evaluated at 3-6 months to give the
patient and provider an opportunity to switch
or modify the type and dosage of HRT.

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Case 1
• Initial Presentation
A 48-year-old woman presents to her primary care physician with a
chief complaint of menstrual irregularity.
• History
The patient’s cycles had been regular until 8 months ago, when she
noted the interval between menses was lengthening. Her normal
menstrual cycle had been a 29-day interval and 5-day duration. Twice,
her cycles changed to 45-day intervals, and now she reports
amenorrhea for the past 5 months. She has experienced mild hot
flushes, disturbed sleep, decreased libido, and emotional lability.

JCOM 2000; 7: 49-63

Case
• For the past 4 years, the patient has been the principal of a local elementary
school, and for 20 years prior to becoming an administrator she was a school
teacher. She becomes tearful when describing her job stress and difficulties
managing her 3 adolescent children. Additionally, her 80-year-old mother with
mild dementia recently moved in with the family. The patient states that her
husband is supportive but has just become principal of the local junior high, which
has significantly increased his job stress. The patient sporadically takes calcium
supplementation. She asks if this is what menopause is all about and if hormones
will help.

Modified from :JCOM 2000; 7: 49-63

Case
Physical Examination

• Blood pressure 146/90 mm Hg, pulse of 88 bpm, respiratory rate 18

breaths/minute, and temperature of 36,8°C. The patient is 168 cm tall and
weighs 86 kg. Head, neck, lung, heart, and abdominal examinations reveal
no abnormalities. Breast examination reveals normal. Pelvic examination
reveals normal external genitalia and dry vaginal mucosa. The cervix is
parous and nontender, and the uterus is mobile and of normal size.
Ovaries are nonpalpable.

Modified from : JCOM 2000; 7: 49-63

Case
1. Berdasarkan paparan kasus tersebut di atas, maka tahapan fungsi
reproduksi pasien adalah :
a. Early perimenopause

b. Late perimenopause

c. Early post menopause

d. Klimakterium
Case
2. Uji diagnostik apa yang diperlukan untuk menegakkan diagnosis ?
a. FSH

b. LH

c. AMH

d. Estrogen

e. Bukan salah satu di atas

Modified from : JCOM 2000; 7: 49-63

 Case
• Further History

The patient is emotional and admits to several life stressors. She has gained 10 kg in
the past year and finds herself eating when she feels overwhelmed. She has been
awakening at 3:00 AM and has trouble going back to sleep. Her 17-year-old
daughter’s grades have dropped significantly; her 15-year-old son was discovered to
have marijuana at a party; but her 11-year-old daughter is doing well. The patient
feels derelict as a mother and does not enjoy time with her family anymore. She
reports being too tired to exercise and has difficulty with concentration, symptoms
she attributes to the multiple demands in her life. She denies suicidal ideations.
Modified from : JCOM 2000; 7: 49-63
 Case
3. Apakah depresi merupakan gejala perimenopause?
a. Benar, kadar estrogen yang berfluktuasi ekstrim mencetuskan depresi

b. Benar, kadar FSH yang tinggi terkait dengan kerentanan terhadap depresi

c. Salah, tidak terdapat keterkaitan antara penurunan hormone estrogen dengan

depresi

d. Salah, tidak terdapat keterkaitan antara gejala vasomotor dengan depresi

e. Benar, depresi terkait dengan adanya gejala vasomotor .

4. If the patient clinically depressed and need management, what is the best
approach to treating depression in this patient?
Modified from : JCOM 2000; 7: 49-63
 Case
3. Apakah depresi pada kasus ini perlu diterapi medikamentosa, preparat
apa yang layak menjadi pilihan pertama ?
a. Perlu diterapi, estrogen dosis terendah yang menghilangkan gejala.

b. Perlu diterapi, SSRI sebagai pilihan pertama

c. Perlu diterapi, golongan tricyclic antidepressant sebagai pilihan prtama

d. Tidak perlu diterapi

Modified from : JCOM 2000; 7: 49-63

 Case
4. Bila kasus ini memenuhi kriteria diagnosis perimenopause, pemeriksaan
laboratorium apa yang tidak diperlukan dalam perencanaan pengelolaan
pasien ?
a. Kadar estrogen serum

b. Profil lipid

c. Kadar Gula Darah

d. TSHS
 Case

5. Bila kasus ini memenuhi kriteria diagnosis perimenopause,

pemeriksaan penunjang apa yang perlu dilakukan untuk
mempertahankan/meningkatkan kualitas hidup pasien ?
a. DXA

b. ECG

c. Mammografi

d. Pemeriksaan rongga pelvis dan apus mukosa cervix

Case 2
A 42-year-old woman presents for
evaluation of abnormal uterine bleeding.
She states that over the past year, her
cycles have become unpredictable. She
reports experiencing depressed mood
and fatigue and complains of hair loss,
dry skin, constipation, and weight gain.
On physical examination, the patient's
hair appears brittle and strawlike

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Case
Which of the following tests is likely to be
the most valuable for making the
diagnosis?

a. Prolactin
b. TSH
c. FSH
d. Beta-hCG

Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD

 Case 3
A 41-year-old woman presents for
evaluation of amenorrhea. She states that
she has regular menstrual cycles every
30 days but has not had one for the past
2 months. She has been feeling
nauseated and has recently noticed that
her bra is fitting more tightly. She denies
experiencing heat or cold intolerance,
night sweats, hot flashes, visual changes,
depressed mood, changes in her sleep,
or any other symptoms.

Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD

 Case

Which of the following is the most likely

cause of this patient's symptoms?

a. Anorexia
b. Pregnancy
c. Pituitary adenoma
d. Premature ovarian failure

Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD

 Case 4
A 45-year-old woman presents for evaluation of
abnormal uterine bleeding. She has noticed that
her cycles have become unpredictable over the
past year, and she recalls occasionally skipping 1
or 2 months between menses. On further
questioning, she cites a history of galactorrhea
and mentions that she has difficulty driving
because she has to turn her head every time she
wants to see the rear-view mirror. A representation
of her visual field test is shown.
Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 Case
Which of the following tests is likely to be
most useful for confirming the diagnosis?

a. Prolactin
b. TSH
c. FSH
d. Beta-hCG

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
 Case 5
A 47-year-old woman presents for evaluation of hot
flashes. She states that over the past year, she has been
suffering from sudden episodes of feeling warm and
sweating profusely, usually take place at night, without
any specific triggers, and last several minutes. She is
concerned because even though she has always had
normal blood pressure, she measured it two nights ago
during one of these episodes and found it to be 190/120
mm Hg. Today, in the clinic, her BP is 118/67 mm Hg.

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014
Case
As confirmed by the image shown, which of
the following organs is most likely to be the
source of this patient's complaints?

a. Thyroid
b. Liver
c. Adrenal gland
d. Bladder

Menopause: Changes and Challenges Juan S Sandoval-Leon, MD; Jason S Yeh, MD; Thomas M Price, MD.Medscape August 5,2014