Villegas, Jose Bernabe

GYNECOLOGY
Vinluan, Joseph David Dr.
Teresa Luna
Wong, Deo Adiel August 2,
2007
Yague, Glenn
3rd Year-D
Yang, Caprice

Case #10
A 45 year old G2P2 (2002) complained of bothersome,
uncomfortable, intermittent episodes of feeling very warm, and
inability to sleep properly since 6 months ago. LMP- May 1st week 2006
PMP Feb 2007. On pelvic examination, the vaginal mucosa was smooth
and pale pink. The cervix was smooth, pale pink, with a parous os; on
internal examination the cervix was long, firm, smooth, movable. The
uterus was normal in size, anteflexed, movable, not tender. No
adnexal masses were appreciated.

1. What additional information should be asked?

Since the patient is experiencing hot flashes, the most common

symptom of menopause, also with the proximity of the patient's age to the
mean age of menopause which is 50, then probing for symptoms that
accompany this condition will be of benefit. According to some studies, hot
flashes occur in as many as 75% of perimenopausal women. We might as
well ask for feelings of nausea or headache, palpitations (describing it to the
patient as feeling a strong heartbeat) or if the patient is very aware of her
body, an increase in her pulsations. These symptoms usually accompany hot
flashes and is very helpful in considering diseases manifesting primarily or
secondarily as vasomotor symptoms. Probing further, ask for feeling of
tiredness during the day. This will be suggestive of insomnia or
sleeplessness, that usually accompanies hot flashes.

Lack of estrogen can manifest as diminished rugation in the vaginal

wall, making it smooth. These gauges us to delve in more to endocrinologic
causes, from hypothalamus, pituitury (microadenoma) down to the ovaries or
adrenals and the feedback that may consequently result from this. Of course,
effects from the HPO axis may well be manifested not only by lack in
rugation of the vaginal wall but, especially if suggestive of pituitary
abnormalities of hormone concentrations, then a collection of other signs
and symptoms like hirsutism, galactorrhea, oliguria or anuria, striae, buffalo
hump, cold/heat intolerance, etc. This requires asking if the patient noticed
these changes that might point to dysfunction in the HPO axis, whether it be
high in nervous system or an end-organ disease. Of course we are not
eliminating age-related causes of changes in gonadal hormone
concentrations.

Hot flashes correspond to marked, episodic increases in the frequency

and intensity of GnRH pulses from the hypothalamus that is the marker for
the same central disturbance of the body temperature regulation center.
This may also be accompanied by fatigue, nervousness, irritability,
depression and memory loss. Hot flashes that occur at night are termed
night sweats and may be responsible for the interruption of sleep patterns.
These and other cardiovascular or neurologic symptoms (eg. dizziness, light-
headedness, vertigo) can also occur, with or without flushing, making the
episode more difficult to classify as simply a climacteric symptom. At the
back of our minds, then it might be symptoms of menopause but because of
the wide range of symptoms, symptomatic women who have risk factors for
a condition other than menopause should undergo thorough evaluation for
symptoms pointing more to cardiac (paroxysmal nocturnal dyspnea) or
neurologic (lateralization of weakness, focal deficits, signs of cranial nerve
involvement, etc.) causes of vasomotor symptoms.

For most older women, a general loss of pelvic tone also occurs, and
this may manifest as weakness (or even prolapse) of reproductive or urinary
tract organs, including the pelvic support (pelvic diaphragm). These needs
asking about feelings of inability to hold urine or urinary incontinence.
Furthermore, urogenital symptoms of vaginal dryness, dyspareunia, dysuria
and/or even pruritus needs consideration as all of these may point to age-
related causes (atrophy in urogenital organs), may point to infectious causes,
even hematologic causes (vascular compromise and consequent ischemia)
or as mentioned above, endocrinologic causes (lack/loss of estrogen).

In addition to alterations in the pelvic organs, marked changes occur

throughout the body in patients of old age. Skin loses elasticity (which may
be attributed to loss of collagen with old age), bone mineral density (BMD)
declines, and dense breast tissue is replaced by adipose tissue. This may
manifest as skin dryness or thinning, noticeable change in posture (no pain),
or changes in the shape of the breast. These things needs inquiring further
because, respectively, this may be a manifestion of immunologic diseases
(connective tissue diseases); endocrinologic causes of bone loss, or trauma;
or neoplasm (especially if there is a marked change not only of the breasts
but of the whole body as well - cachexia), metabolic or endocrinologic causes
of losing weight.

Signs of depression may be apparent in old age which may be

attributed to falling of estrogen levels that reduce dopamine receptor
sensitivity or reduce available tryptophan for serotonin synthesis, leading to
reduced activity of central nervous system transmitters and consequent
depression. This may be aggravated by psychosocial stressors like changes
in relationships with children, marital status, and other life events. So any
depressive symptoms should be asked as well as family and lifestyle changes
that might accompany it.

Smoking history should be asked because it predisposes to

cardiovascular disease, osteoporosis, and early skin aging. All of which may
be prominent in women of old age.

A family history of endometrial and breast cancer must be assessed for

there is decreased progesterone levels in menopause. Progesterone protects
the endometrium from excess estrogen stimulation by directly regulating
estrogen receptors but because of the decreased levels, there is also
decreased inhibition of the trophic effects of estrogen which may lead to
endometrial hyperplasia and cancer. The same mechanism happens in the
breast ductal epithelium from unopposed stimulation by estrogen in the
absence of progesterone that increases the risk for breast cancer.

Cardiovascular diseases like coronary artery disease and

cerebrovascular disease must also be included in the assessment of our
patient since she’s already 45 years old and hypoestrogenemia is a major
contributing factor for these diseases. Estrogen tends to increase the levels
of HDL but in menopause the ratio is shifted in favor of LDL which is the bad
cholesterol. A history of hypertension along with other systemic diseases
like diabetes mellitus and hypercholesterolemia increases the risk and thus,
also pertinent.

The risk for osteoporosis must be evaluated in our patient for the rate
of bone loss increases to as high as 5% per year in estrogen-deficient women
for hypoestrogenemia has a direct effect on osteoblast function and appears
to exert its adverse effects by altering calcium balance. A positive family
history is also a risk factor predisposing to osteoporosis or secondarily
contributing to osteoporosis in menopause since heredity determines the
peak bone mass and the rate of bone loss after the age of 30.

2. What is the probable diagnosis?

The patient is experiencing symptoms of

estrogen deficiency, manifested by hot flashes,
which she described as bothersome,
uncomfortable, and intermittent episodes of
feeling very warm, and sleep disturbances.
Since the patient is already in her late forties
and it has not been 1 year from her last menstrual period, she is most likely
in the perimenopausic period.

To distinguish perimenopause from menopause, perimenopause refers

to the time before menopause when vasomotor symptoms and irregular
menses often commence; it can start 5-10 years or more before menopause.
During the menopausal transition, a woman
HOT FLASH!
may begin to experience symptoms of by Nancy Goodman Lawrence
estrogen deficiency such as hot flashes, sleep
disturbances, abnormal bleeding and may lose
bone density, even though she is still menstruating. During this period,
ovarian follicles become increasingly resistant to FSH stimulation despite
normal levels of estradiol. Ovulation is less frequent, and progesterone
production is decreased.

Menopause, by definition, begins 12 months after the final menses and

is characterized by a continuation of vasomotor symptoms and by urogenital
symptoms such as vaginal dryness and dyspareunia. Most women
experience menopause between the ages of 48-55 years. If menopause
occurs before 40 years, it is considered premature. It is late if it occurs after
55 years. Women who smoke, who have never been pregnant, and who live
at high altitudes are more likely to experience menopause at a slightly earlier
age.

Menopause is physiologically correlated with a decrease in estrogen

secretion resulting from the loss of follicular function. The decrease in
estrogen is due to decreased secretion from the ovaries. However,
peripheral aromatization of estrogen by muscle and fat still occur.

Other hormones that are affected by menopause include progesterone

and androgens, i.e. testosterone & androstenedione. Progesterone
production stops completely while total androgen production decreases. The
ovaries stop producing progesterone, such that typical premenstrual
symptoms do not appear. This may leave the endometrium and breast
tissue unprotected against unopposed estrogen stimulation, thereby
increasing the risk of both endometrial & breast cancer. The ovaries also
decrease androgen production, as do the adrenals. However, circulating
concentrations of androgens do not change at menopause.

The patient’s level of FSH is expected to be elevated secondary to

decreased inhibin production by her ovarian follicles and increased ovarian
resistance to FSH. Once her FSH levels are found to be greater than 40 U/L,
complete cessation of ovarian function can be said to have occurred. This is
consistent with the definition of menopause, which includes amenorrhea,
with signs of hypoestrogenemia and an elevated serum follicle-stimulating
hormone (FSH) of greater than 40 U/L.
 Hot flashes, the most common symptom of menopause (which the
patient reported as episodes of feeling very warm) correspond to marked,
episodic increases in the frequency & intensity of GnRH pulses from the
hypothalamus, which serves as a marker for the central disturbance of the
body temperature regulation center responsible for the hot flashes.
Commonly, the hot flash may begin with a feeling of nausea or a headache,
followed by a wave of heat, flushed skin, and palpitations (feeling a strong
heartbeat). Women having hot flashes often have an increase in their skin
temperature and pulse. Hot flashes often cause insomnia or sleeplessness,
which can contribute to tiredness during the day. This was one of the
complaints of the patient with her inability to sleep.

Aside from hot flashes, other symptoms the patient may experience
during this period are the following:
• Menstrual irregularities - the intervals may be longer or shorter, flow
may be scanty to profuse, and may skip some periods. As ovulation
becomes more erratic, the lower levels of progesterone may lead to
longer and heavier periods.
• Urinary incontinence and irritation - Low estrogen levels may make her
more vulnerable to urinary or vaginal infections. Loss of tissue tone
may contribute to urinary incontinence.
• Vaginal changes - when estrogen levels diminish, vaginal tissues may
lose lubrication and elasticity, causing dyspareunia and may note a
change in vaginal discharge.
• Breast changes - Women may see changes in the shape of their
breasts.
• Bone loss - Rapid bone loss is common during the perimenopausal
years. Most women reach their peak bone density between the ages of
25-30 years. After that, they lose an average of 0.13% per year. During
the perimenopause, bone loss accelerates to about a 3% loss per year.
Later, it drops off to about a 2% loss per year. There usually is no pain
associated with bone loss. However, bone loss can cause osteoporosis,
which places a woman at an increased risk of fracture.
• Cholesterol - A woman's cholesterol profile also changes significantly at
the time of menopause. Total cholesterol and low density lipoprotein
(LDL) cholesterol increase. Increased LDL cholesterol is associated with
an increased risk of coronary artery disease.
• Weight gain - A 3-year study of healthy women nearing menopause
found an average gain of 5 pounds during this time. It is unclear
whether this gain is due to aging or to hormonal changes.
• Decreasing fertility - As ovulation becomes irregular, the ability to
conceive decreases. Although fertility declines, pregnancy can still
occur, as demonstrated by a relatively high rate of unintended
pregnancies in women aged 40-44 years. In fact, the number of
 unintended pregnancies in this age group has increased over the past
decade (Henshaw, 1998).
• Changes in sexual function - During perimenopause, sexual arousal
and desire may change, because the ovaries also may decrease their
production of testosterone—a hormone involved in a woman's libido, or
sexual drive.
• Mood changes - Some women experience mood swings, irritability or
depression during perimenopause, but the cause of these symptoms
may be sleep disruption or other menopausal symptoms more than the
hormonal changes of menopause.

Depression linked to earlier perimenopause. The

Harvard Study of Moods and Cycles found that women with a
history of depression are more likely to experience
menopausal symptoms at an earlier age, and those with the
most severe depressive symptoms who were receiving
antidepressants had the greatest risk of an earlier
perimenopause.

Women with any history of depression were 20% more

likely to begin having menopausal symptoms earlier than
those who never had depression, study author Bernard L.
Harlow, PhD, of Harvard's Brigham and Women's Hospital in
Boston, Massachusetts. Archives of General Psychiatry. Jan.
13, 2003;60:29-36

3. What work-up should be done?

The diagnosis of perimenopause can usually be made by reviewing a

woman’s medical history. The most common symptoms women notice are
changes in menstrual periods and the onset of hot flashes. Menopause, as
was mentioned above, is confirmed when a woman has had no menstrual
bleeding for 12 consecutive months.

In most cases, hormone tests aren’t reliable because in menstruating

women, hormone levels are changing all the time. However, in younger
women when menstrual irregularity is
infrequently a sign of menopause, hormone testing may be more valuable to
confirm that
menopause has indeed occurred. Sometimes testing is done to check specific
hormone levels,
especially when fertility is an issue. This can help women make decisions
about beginning
or adjusting medications. For some women, it may make sense to test for
other causes
of symptoms that can mimic perimenopause, such as thyroid disease.
 Sometimes, elevated follicle-stimulating hormone (FSH) levels are used
to confirm
menopause. FSH is a hormone produced by the pituitary gland that triggers
the ovaries
to secrete estrogen. As the ovaries’ production of estrogen declines, the
pituitary gland tries
to stimulate estrogen production by releasing more FSH into the blood. When
a woman’s
FSH blood level is consistently elevated to 30 mIU/mL or higher, and she is
no longer
having menstrual periods, it is generally accepted that she has reached
menopause. FSH levels above 10 to 12 mlu/ml may indicate that the ovaries
are starting to fail. In other words, this means that the patient is in
perimenopause or is having a "diminished ovarian reserve."

However, a single FSH level can be misleading in perimenopause since

estrogen production doesn’t fall at a steady rate from day to day. Instead,
both estrogen and FSH levels
fluctuate from fairly high to fairly low during perimenopause. Therefore, one
test with an
elevated FSH level is not usually enough to confirm menopause. More
important, a low
FSH in a woman who is having hot flashes and changing periods does not
eliminate the
likelihood of perimenopause. Also, if a woman is using certain hormone
therapies (such as
birth control pills), an FSH test isn’t valid.

Estradiol is the primary human estrogen and when the ovaries begin to
fail, the circulating estradiol levels drop. A serum estradiol concentration
test can be given to measure the amount of estradiol in the blood. In this
case, estrogen levels that are lower than normal would signal ovarian failure,
or early menopause. The normal estradiol day 3 value is about 25-75 pg/ml.
Generally, estradiol levels about 30 or below in conjunction with a high FSH
level (high in this case, meaning in the post-menopausal range, i.e. 30-40 or
higher) is considered menopausal. However it is important to note that if the
FSH hasn't reached post-menopausal levels and estradiol is on the low side,
it is not considered early menopause. There can be other reasons for low
estradiol, including excessive exercise, low body fat, and diminished ovarian
reserve. This is because estradiol levels tend to drop over time. During the
first 2 to 5 years following menopause or ovarian failure, blood levels of
estradiol drop to an average range of about 25 to 35 pg/ml. Women not on
HRT generally will see this number drop even more over time; after about
five years, it's common for menopausal women who aren't on HRT to have
estradiol levels below 25.
 Progesterone. Most labs and studies state that menopausal levels are
about .03-.3 ng/ml. By way of comparison, premenopausal women will have
progesterone levels at about 7-38 ng/ml during their luteal phase.

Leutinizing Hormone. Normal day 3 LH levels are 5-20 mlU/ml. If the

LH levels are high in ratio to FSH levels, this could indicate that the patient is
not in menopause or going through premature ovarian failure, but instead
have polycystic ovarian syndrome (PCOS) which can cause some similar
symptoms. Additionally, clinical data can also show PCOS which can help in
ruling out the condition.

Thyroid hormone levels are checked from the blood in order to

distinguish menopause from thyroid disease. Hot flashes, insomnia,
irritability, palpitations and "fuzzy thinking" are common symptoms of both.
Abnormal levels of TSH may indicate thyroid disease rather than menopause.
However, incidence of both occurring together should not be overlooked.

With Salivary Testing, samples of the patient’s saliva are taken to see
the levels of hormones that are being produced and to determine if there are
any deficiencies. Unlike the blood tests, the saliva hormone tests will show
the levels of free hormones. Because about 95% or more of the blood
hormones are bound, the saliva tests measure only the remaining 1 to 5% so
the results may be markedly lower than that which can be seen in the results
of the blood tests.

Ultrasound. In some cases, high resolution ovarian ultrasound to view

your ovaries may be performed. This will determine whether the patient still
has any eggs and follicles. However, generally, this information doesn't help
that much. According to a British study, up to two-thirds of women diagnosed
with premature ovarian failure do indeed have remaining follicles. The
problem is, even when eggs are detected, attempts to stimulate ovulation
through hormones have been relatively unsuccessful. However, ultrasound
may make sense if the patient is in the early stages of premature
menopause and are intending to pursue an aggressive fertility program.

Treatment. Oral contraceptives are often the most effective treatment

to relieve perimenopausal symptoms — even if the patient doesn't need
them for birth control. Low-dose pills regulate periods and reduce hot flashes
and vaginal dryness.

References:
• Berek, Jonathan S., Novak’s Gynecology, 14th ed.

• www.emedicinehealth.com/menopause/article_em.htm
• http://menopause.upmc.com/Treatment.htm

• http://emc.medicines.org.uk/eMC/assets/c/html/DisplayDoc.asp?DocumentID=16569

• http://www.emedicine.com/aaem/topic305.htm

• http://www.menopause.org/edumaterials/earlyguidebook/menopausebasics.pdf

• http://www.menopause.org/edumaterials/cliniciansguide/cliniciansguidetoc.htm

• http://www.earlymenopause.com/tests.htm

• http://thyroid.about.com/cs/pregnancy/a/menopause.htm

• http://www.mayoclinic.com/health/perimenopause/DS00554/DSECTION=8