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Menstrual cycle

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Title: Menstrual cycle


1
Menstrual cycle
  • Wilfried Karmaus
  • Reproductive Epidemiology
  • EPI 824

2
Overview
  • Number of germ cells (oocytes)
  • Menarche
  • Menopause
  • Menstrual cycle
  • Endocrine regulation
  • Menstrual cycle disorders
  • Cycle irregularities
  • Polycystic ovary syndrome
  • Endometriosis

3
Number of oocytes at different ages
Age of cells
3-6 weeks of gestation Endoderm of the yolk sac 10,000
8 weeks Proliferation by mitosis 600,000
8-20 Mitosis, meiosis, atresia 6-7,000,000
20-40 weeks 80 loss 1-2,000,000
Birth to puberty Loss to atresia 300,000
Reproductive years Ovulation 400-500
4
  • Mitosis is the process that facilitates the equal
    partitioning of replicated chromosomes into two
    identical groups (Each daugther cell will have a
    complete set of chromosomes).
  • Meiosis Process by which a single parent diploid
    cell  divides to produce four daughter haploids
    cells (One homologous chromosome of the pair).

5
Menarche
  • Puberty gradual transition form immaturity to
    functional capability of reproduction
  • Menarche is the first ovarian controlled uterine
    bleed in a womens lifetime
  • Average age at menarche 13 years
  • Normal range in girls
  • Onset 9-13
  • Completion 12-17

6
Menarche
  • The average age of menarche in industrialized
    countries declined by 3 years from 1860 to 1965
    (secular trend).
  • Age at menarche appear earlier in countries with
    the longest life expectency (poor nutrition
    delays age at menarche).

7
Menarche
  • Peak growth precedes the first menstruation
  • 5 stages Marshall and Tanner
  • Thelarche breast building (5 stages)
  • Pubarche appearance of pubic hear (5 stages)
  • Gonadarche gonadal maturation
  • Adrenarche adrenal androgen secretion

8
Menopause
  • The menopause is the time of a woman's life when
    her reproductive capacity stops
  • No period for 12 months
  • The ovaries cease functioning and they produce
    fewer hormones.
  • The body undergoes a variety of changes both
    because the ovaries stop functioning and because
    of aging.
  • The menopause is sometimes marked by unpleasant
    symptoms but, even though some may be disabling,
    none is life-threatening.

9
Menopause
  • The number of follicles in the ovary determines
    the age at which the menopause takes place.
  • The number declines steadily until around age 40
    and then becomes more rapid until after the
    menopause when essentially there are no follicles
    left.
  • After menopause, the typical pattern of the
    hormones is
  • Continually high levels of FSH and
  • Continually low levels of estrogen and
    progesterone.

10
Stages of the climacteric
  • Climacteric 47-55 years

Premenopause 5 years before
Menopause
Postmenopause starts 1 year after menopause
Perimenopause transitional phase between pre-
and postmenopause 2 years before and 1 year after
11
Menopause
  • The changes in hormone production affect various
    parts of the body, for instance the bones and the
    cardiovascular system.
  • Various hormonal therapies (hormone replacement
    therapyHRT) have been tried to lessen the
    consequences of the menopause.
  • HRT has in turn raised concerns with regard to
    increased risk of diseases such as cancer.

12
Menopause
  • Hot flushes and night sweats are characteristic
    of the menopause. Hot flushes arise as a sudden
    feeling of heat in the face, neck and chest.
    Night sweats are the night-time manifestation of
    hot flushes.
  • Insomnia is often cited as a menopausal
    complaint, but it usually occurs as a secondary
    effect of sleep disruption caused by the night
    sweats.
  • Flushes may be induced by tension or nervousness
    and their frequency.

13
Prevalence of hot flushes
  • Mayan women 0
  • Hong Kong women 10-22
  • Japanese women 17
  • Thai women 23
  • North American 45
  • Dutch women up to 80.

14
Menopause
  • In general flushes and sweats are more common
    in European and North American women than in
    other populations.
  • A high intake of dietary phytoestrogens
    (estrogen-like compounds found in plants) has
    been suggested as a possible explanation of the
    lower frequency of menopausal symptoms in
    Japanese as compared with Caucasian women.

15
Menopause
  • The average age at menopause is about 51 years in
    industrialized countries. The age tends to be
    lower in women who smoke and in those who have
    had no children.
  • Lower age at menopause may also be related to
    poor socioeconomic status.
  • Women with menstrual cycles averaging less than
    26 days seem to reach the menopause 1.4 years
    earlier than those with longer cycles.
  • It is also believed that a woman's age at
    menopause may be a biological marker of aging,
    and that a later menopause may be associated with
    greater longevity.

16
Menstrual cycle Timing
  • Follicular phase day 1-14, menses day 1-5
  • Ovulatory phase day 14-16
  • Luteal phase day 16-28

17
Menstrual cycle Days 1-5 Estrogen Falls, FSH
Rises. Menstrual bleeding begins on Day 1 of the
cycle and lasts approximately 5 days. During the
last few days prior to Day 1, a sharp fall in the
levels of estrogen and progesterone signals the
uterus that pregnancy has not occurred during
this cycle. This signal results in a shedding of
the endometrial lining of the uterus.
Figure taken from Robert J. Huskey
18
Since high levels of estrogen suppress the
secretion of FSH, the drop in estrogen now
permits the level of follicle stimulating hormone
(FSH) to rise. FSH stimulates follicle
development. By Day 5 to 7 of the cycle, one of
these follicles responds to FSH stimulation more
than the others and becomes dominant. As it does
so, it begins secreting large amounts of
estrogen.
19
  • Days 6-14 Estrogen Is Secreted, FSH Falls.
  • Estrogen is secreted by the follicle during this
    phase of the menstrual cycle. It
  • stimulates the endometrial lining of
    the uterus
  • suppresses the further secretion of FSH.

Figure taken from Robert J. Huskey
20
At about mid-cycle (Day 14), the estrogen helps
stimulate a large and sudden release of
luteinizing hormone (LH). This LH surge, which
is accompanied by a transient rise in body
temperature, is a sign that ovulation is about to
happen. The LH surge causes the follicle to
rupture and expel the egg into the Fallopian
tube.
21
  • Days 14-28 Estrogen And Progesterone Secretion
    First Rise, then Fall.
  • After rupture of the follicle, it is transformed
    into the corpus luteum and produces progesterone.
  • P supports to prepare the endometrial lining for
    implantation of the fertilized egg.
  • (If the egg is fertilized, a small amount of
    human chorionic gonadotrophin (hCG) is released
    that stimulates further progesterone production.)

Figure taken from Robert J. Huskey
22
After implantation, the trophoblast will secrete
human Chorionic Gonadotropin (hCG) into the
maternal circulation. HCG keeps the corpus luteum
viable.The corpus luteum continues to produce
estrogen and progesterone, which keep the
endometrial lining intact. By about week 6 to 8
of gestation, the newly formed placenta takes
over the secretion of progesterone. If the egg
is not fertilized, the corpus luteum shrinks, and
the levels of estrogen and progesterone drop,
the uterus sheds its lining, and menstruation
begins. In addition, with no estrogen to
suppress it, FSH levels again start to rise.
Thus, one cycle ends and another begins.
23
Stages of follicle growth
Growth 335 days
20-30
Atresia
Selection 10 days
?80
Maturation 10 days
Initiation
24
Endrocrine control of the menstrual cycle
Early to mid-follicular phase
Late follicular phase ovulation
Hypothalamus
Hypothalamus
GnRH
GnRH
Pituitary gland
Pituitary gland
FSH
LH
FSH
LH
Follicle
Follicle
Granulosa cells
Theca cells
Granulosa cells
Theca cells
Inhibin
Androgens
Estrogens
Androgens
High estrogens
low progesterone
Feedback negative
positive
25
Pathway of steroid hormones
Cholesterol (mitochondria)
Dehydro-epiandrosterone
Pregnenolone
Androstenediol
Androstenedione
Testosterone
Progesterone
Aromatase
Aromatase
Estrone
Estradiol
Cortisol
26
  • Estrogens stand for a group of hormones
  • Estradiol (approximately 10-20 of circulating
    estrogens)
  • Estrone (approximately 10-20 of circulating
    estrogens)
  • Estriol (approximately 60-80 of circulating
    estrogens)
  • Estradiol is produced by the ovaries. It is the
    primary circulating estrogen before menopause. It
    is also the strongest estrogen and is responsible
    to the monthly ovulation and normal menstrual
    cycles.
  • Estrone is produced by the fatty tissues. It is
    less potent than estradiol, but more important
    after the menopause
  • Estriol is an estrogen that is prominent mostly
    during pregnancy.

27
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28
Progesterone is made by the adrenal glands in
both sexes and by the testes in males. It is a
precursor of testosterone and of all the
important adrenal cortical hormones.
Progesterone is made from the sterol
pregnenolone that derives from cholesterol,
Progesterone stimulates the growth of a
endometrial lining, prepares breast tissue for
the secretion of breast milk, and generally
maintains the advancement of pregnancy.
29
  • Androgens stands for a group of primarily male
    hormones
  • testosterone
  • androstenedione
  • dehydroepiandrosterone).
  • Androgens are also produced in the ovaries.

30
Menstrual cycle irregularities1. abnormal
frequency
Kaltenbach chart
Duration 28 d ?5 Amount 3-5 pads
or tampons (?35 mL)



Normal cycle
Abnormal frequencyoligomenorrhea



Duration gt 35 days
Abnormal frequencypolymenorrhea



Duration lt 22 days
31
Menstrual cycle irregularities2. abnormal
amount of duration



Duration 28 d ?5 Amount 3-5 pads
or tampons
Normal cycle



Hypomenorrhea
Amount lt 2 per day



Hypermenorrhea
Amount gt 5 per day



Menorhagia
Duration 7-14 days
32
Menstrual cycle irregularities3. others
  • Spotting bleeding unrelated to menses
  • Ovulatory bleeding
  • Metorrhagia gt 14 days, no clear cycle
  • Amenorrhea absence of bleeding for more
    than 3 months

33
Menstrual cycle irregularitiesprevalence and
risks
  • 9-30 of reproductive-aged women have menstrual
    irregularities requiring medical evaluation.
  • Regular vigorous exercise is associated with
    decreased estrogen levels in the blood.
  • Healthy women who began training for a marathon
    developed new menstrual cycle irregularity.
  • Any risk factor that may alter endocrine control
    (e.g. stress, endocrine disruptor) can result in
    cycle irregularities.

34
Menstrual cycle irregularitiescauses
  • Menstrual period changes are usually a symptom of
    endocrine imbalance.
  • Changes in the amount or timing of hormones
    released by the thyroid, adrenal and pituitary
    glands, or hypothalmus may cause the ovary to
    delay or skip ovulation.

35
Menstrual disorders
  • Irregular patterns of bleeding
  • Hypothalamic ovarian insufficiencyPsychogenic
    stress, anorexia nervosa
  • Pituitary causesfor instance acromegaly
    increased somatotropic
    hormones (STH) Cushings diseas
    impaired cortisol rhythm
  • Ovary polycystic ovary
  • Thyroid ? hypothyroidism anovulatory
    cylces and dysfunctional bleeding
  • ? hyperthyroidism
    hypomenorrhea/ oligomenorrhea
  • Adrenal Cushings syndrome impaired cortisol
    rhythm

36
Polycystic Ovary Syndrome (PCOS)
  • PCOS is a common cause of menstrual irregularity
    in premenopausal women.
  • According to the initial description by Stein and
    Leventhal in 1935, the diagnosis of PCOS was
    based on the clinical symptoms (oligo/amneorrhea,
    infertility, hirsutism, and obesity) in the
    presence of histologically verified polycystic
    ovaries.
  • PCOS affects between 3-10 of women of
    reproductive age.

37
Polycystic Ovary Syndrome (PCOS)
  • The ovaries contain many small follicles or
    cysts. Each has an egg, but they do not grow
    normally and shrink before ovulation. Each month,
    new follicles develop and shrink into cysts.
  • The fertility is reduced.
  • Most PCOS cases are unexplained.
  • The disorder may be inherited.
  • Deficiency in luteinizing hormone (LH)
  • Resistance to insulin. A similar effect on the
    ovaries can occur in women with eating disorders
    (anorexia or bulimia), or women whose bodies do
    not properly make estrogen and other steroids
    (for example, women with congenital adrenal
    hyperplasia).

38
Endometriosis
  • Endometriosis is a condition where endometrium
    (the lining of the uterus) is found in locations
    outside the uterus
  • Ovaries
  • Uterus
  • Bowel
  • Bladder
  • Utero-sacral ligaments (ligaments that hold the
    uterus in place)
  • Peritoneum (covering lining of the pelvis and
    abdominal cavity)
  • On rare occasions other distant sites.

39
Endometriosis
  • The tissue reacts to estrogen and progesterone
  • same cyclic responses as the endometrium
  • Some therapies for endometriosis attempt to
    reduce estrogen production.
  • Endometriosis causes pelvic pain.
  • Endometriosis is affecting approximately
  • 7 of reproductive-aged women
  • 10 - 15 of women undergoing diagnostic
    laparoscopy,
  • 30 -40 of infertile women having laparoscopy,
  • 14 - 53 of women with pelvic pain.

40
Endometriosis - Causes
  • Retrograde menstruation Endometrial cells from
    the uterus are pushed backward through the
    fallopian tubes and exit into the abdomen where
    they implant and grow.
  • Embryonic tissueEndometrial tissue was present
    abnormally when the woman was an embryo. The
    tissue becomes active in reproductive life.  
  • Genetic explanation Women with endometriosis
    frequently come from families with a high
    incidence of the disease.

41
Endometriosis - Causes
  • Lymphatic distributionEndometrial material gets
    distributed throughout the body via the lymphatic
    system.
  • Immune system dysfunctionWomen with
    endometriosis have been found to carry cells with
    reduced ability to attack abnormal cells and
    high levels of autoantibodies that attack their
    own cells.
  • Environmental influences A study, designed to
    examine the affects of dioxins on reproduction in
    rhesus monkeys, found that 79 of the monkeys
    exposed to dioxins developed endometriosis.

42
Summary
  • Begin and end of reproductive period varies
    between different societies.
  • Menstrual cycle irregularities and disorders are
    frequent (3-30) and can be determined with
    standardized charts.
  • Events of/in the reproductive period, such as age
    at menarche, irregularities, age at menopause,
    etc. are markers for increased risk for health
    outcomes in later life.
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