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MENSTRUAL PHYSIOLOGY
HHD 2015 PART 2
Paula J. Adams Hillard, MD
Professor,
Department of Obstetrics and Gynecology
3
OBJECTIVES
At the conclusion of this presentation, the student should be able to:
• Describe the physiology of the normal menstrual cycle with regard
to events taking place in the hypothalamus, pituitary, ovary, and
uterus/endometrium
• Draw a representation of pituitary and ovarian hormones
throughout the normal menstrual cycle
• Describe the evidence-based “normal menstrual cycle” with regard
to menarche, menstrual frequency, duration, menstrual volume,
and menopause
• Describe the pathophysiology of reproductive dysfunction
4
Downloaded from: StudentConsult (on 10 November 2011 03:52 AM)
© 2005 Elsevier
8
Puberty
 Pubertal events:
◦ In childhood, LH/FSH are suppressed (low levels of
estrogen suppress gonadotropins= neg feedback)
◦ Escape from this suppression and decreased
sensitivity to negative feedback of estrogen
◦ Increased amplitude and frequent of GnRH pulses
provoke progressive enhancement of FSH and LH
secretion and increasing estrogen secretion
◦ Sleep-associated LH release with increasing GnRH
pulses
9
Puberty
 Pubertal events:
◦ Adrenarche: increased adrenal androgen production
 growth of pubic and axillary hair
 control mechanisms likely separate from H-P-O maturation
◦ Decreasing repression of the “gonadostat”
◦ Gradual amplification of GnRH-gonadotropin and
gonadotropin-ovarian steroid interactions leading to
“gonadarche”
10
Sexual Maturity Rating/”Tanner Staging”
11
Puberty
 Menarche: mid-pubertal
 Menarche in relationship
to pubertal development
 Pathways through puberty
◦ Breast development first
◦ PH first
12
PUBERTY
Earlier onset than previously
thought
Racial differences—
• AA girls earlier than
Caucasians
• Little data on other racial
groups
Menarche ~ 12.2-12.8—little
change in ~ 50 years for
Caucasian girls
Wyshak and Frisch, NEJM 1982
1800 1980
13
MENSES: What’s Normal? The Textbook
Answers
Menarche—average 12.8 yo
• Precocious puberty—pubertal development prior to age 8
• Primary amenorrhea– no periods by age 16
Early cycles anovulatory and irregular
Typical menstrual cycles 28 days
Amenorrhea defined as 6 months no periods
Bleeding 2-7 d
Mean blood loss/cycle 30cc (20-60)
• Chronic loss> 80cc associated with anemia
14
MENSTRUATION: What’s Normal?
The REAL Answers, Evidence-Based
Menarche—average 12.8 yo FOR CAUCASIAN girls
• AA girls slightly younger ~ 12.2 yrs
• Mexican-American girls intermediate between Caucasian and AA
Changes in onset of pubertyPUBERTY
• At age 8, 48% of AA girls had pubertal development vs 15% Caucasian girls
• ? Due to increasing obesity/BMI/overnutrition vs endocrine modulators
Primary Amenorrhea:
• No periods by age 15;
• No breast development by age 13
15
 Precocious Puberty
•Previous definition: <8 yo
for girls, based on small
non-diverse population
•New large data set
17,000- PROS
 Peds Endocrine Society has
proposed new guidelines
PUBERTAL DEVELOPMENT
New guidelines propose that
breast or pubic hair
development should be
evaluated only if
 1 or both of these occur
before age 7 in white girls
or
• Before age 6 in AA girls.
Kaplowitz PB et al., Pediatrics 1999 Oct; 4:936-940
16
MENSTRUATION: What’s Normal?
The REAL Answers, Evidence-Based
Early cycles for adolescents are anovulatory and irregular
– But not “anything goes”
– Overall trend toward shorter and more regular cycles through adolescence
Normal Menstrual Cycle length
– Adolescents ~19-45 days
– Adult women 21-38 days
Amenorrhea defined as no periods for 90 days
Bleeding 2-7 days
Mean blood loss/cycle 30cc (20-60)
– Chronic loss> 80cc associated with anemia
17
Vollman RF. The Menstrual Cycle. Major Problems in Obstetrics and Gynecology.
Vol 7. Friedman EA, ed. W.B. Saunders Co., 1977.
31,645 cycles reported by 656 women
MENSTRUAL NORMS IN ADULT WOMEN
Fraser, I.S., et al., Can we achieve international agreement on terminologies and definitions used
to describe abnormalities of menstrual bleeding? Hum Reprod, 2007. 22(3): p. 635-43.
19
MENOPAUSE--DEFINITION
Cessation of Menses-FMP (final menstrual period)
• X 1 year
Average age 50-51
Ethnicity:
• AA: 6-12 mos earlier than Caucasions ?
• Mexicans: 1 year earlier than Caucasions
• Japanese: 5 months later
MENOPAUSAL TRANSITION
 Increased variability of cycles transition to Long Cycles
 Early age at menopause related to:
 Smoking
 Lower SES
 Older age at menopause related to:
 Longer cycles throughout reprod life
 Longer more variable cycles prior to menopause
 Higher parity
 Use of COC
DURATION OF MENOPAUSAL TRANSITION
•Median age at entry is 45.5
•Marker for FMP
•Onset of 90 day cycle
•Earlier onset of 90 d cycle predicts earlier FMP
•1-3 yrs from 90 d cycle to FMP
•Median duration of the transition is 4.8 years
•Range of 1-11 years
Treloar, A.E., et al., Variation of the human menstrual
cycle through reproductive life. Int J Fertil, 1967.
12: p. 77-126.
The Stages of Reproductive Aging +10 staging system for reproductive aging in women
23
24
Randolph et al, JCEM
2011;96:746-54
FSH and
FMP
25
PATTERNS OF MENOPAUSAL TRANSITION
 Increasing variability followed by increasing cycle length--
”typical”
 “Just stopped”
 History of long or irregular cycles
 Increased variability and long cycles and then “revert” to
prior, less variable pattern
26
Vollman RF. The Menstrual Cycle. Major Problems in Obstetrics and Gynecology.
Vol 7. Friedman EA, ed. W.B. Saunders Co., 1977.
31,645 cycles reported by 656 women
27
Age and Gonadotropins
CASES: Feedback
28
• 16 yo girl
• Primary amenorrhea
• DDx:
• Labs:
CASE
29
• 16 yo girl
• Primary amenorrhea
• High FSH
• High LH
• Estradiol =
• Etiology =
• Therapy =
CASE
30
• 16 yo girl
• Primary amenorrhea
• Low FSH
• Low LH
• Estradiol =
• Etiologies =
• Therapy =
CASE
31
• 24 yo woman
• Infrequent periods
• Normal FSH
• High LH
• Estradiol =
• Etiology =
• Therapies =
• Implications for future health =
CASE
32
• 29 yo woman
• Secondary amenorrhea
• Elevated FSH
• Elevated LH
• Estradiol =
• Etiology =
• Therapy =
CASE
33
• 45 yo woman
• Infrequent periods
• Elevated FSH
• Estradiol =
• Etiology =
• Therapy =
CASE
34
• 45 yo woman
• LMP 13 months ago
• Elevated FSH
• Estradiol =
• Etiology =
• Therapy =
CASE
35

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inde222-11-10-2015-09-lect-Hillard-1.ppt

  • 1. 1
  • 2. MENSTRUAL PHYSIOLOGY HHD 2015 PART 2 Paula J. Adams Hillard, MD Professor, Department of Obstetrics and Gynecology
  • 3. 3 OBJECTIVES At the conclusion of this presentation, the student should be able to: • Describe the physiology of the normal menstrual cycle with regard to events taking place in the hypothalamus, pituitary, ovary, and uterus/endometrium • Draw a representation of pituitary and ovarian hormones throughout the normal menstrual cycle • Describe the evidence-based “normal menstrual cycle” with regard to menarche, menstrual frequency, duration, menstrual volume, and menopause • Describe the pathophysiology of reproductive dysfunction
  • 4. 4
  • 5.
  • 6. Downloaded from: StudentConsult (on 10 November 2011 03:52 AM) © 2005 Elsevier
  • 7.
  • 8. 8 Puberty  Pubertal events: ◦ In childhood, LH/FSH are suppressed (low levels of estrogen suppress gonadotropins= neg feedback) ◦ Escape from this suppression and decreased sensitivity to negative feedback of estrogen ◦ Increased amplitude and frequent of GnRH pulses provoke progressive enhancement of FSH and LH secretion and increasing estrogen secretion ◦ Sleep-associated LH release with increasing GnRH pulses
  • 9. 9 Puberty  Pubertal events: ◦ Adrenarche: increased adrenal androgen production  growth of pubic and axillary hair  control mechanisms likely separate from H-P-O maturation ◦ Decreasing repression of the “gonadostat” ◦ Gradual amplification of GnRH-gonadotropin and gonadotropin-ovarian steroid interactions leading to “gonadarche”
  • 11. 11 Puberty  Menarche: mid-pubertal  Menarche in relationship to pubertal development  Pathways through puberty ◦ Breast development first ◦ PH first
  • 12. 12 PUBERTY Earlier onset than previously thought Racial differences— • AA girls earlier than Caucasians • Little data on other racial groups Menarche ~ 12.2-12.8—little change in ~ 50 years for Caucasian girls Wyshak and Frisch, NEJM 1982 1800 1980
  • 13. 13 MENSES: What’s Normal? The Textbook Answers Menarche—average 12.8 yo • Precocious puberty—pubertal development prior to age 8 • Primary amenorrhea– no periods by age 16 Early cycles anovulatory and irregular Typical menstrual cycles 28 days Amenorrhea defined as 6 months no periods Bleeding 2-7 d Mean blood loss/cycle 30cc (20-60) • Chronic loss> 80cc associated with anemia
  • 14. 14 MENSTRUATION: What’s Normal? The REAL Answers, Evidence-Based Menarche—average 12.8 yo FOR CAUCASIAN girls • AA girls slightly younger ~ 12.2 yrs • Mexican-American girls intermediate between Caucasian and AA Changes in onset of pubertyPUBERTY • At age 8, 48% of AA girls had pubertal development vs 15% Caucasian girls • ? Due to increasing obesity/BMI/overnutrition vs endocrine modulators Primary Amenorrhea: • No periods by age 15; • No breast development by age 13
  • 15. 15  Precocious Puberty •Previous definition: <8 yo for girls, based on small non-diverse population •New large data set 17,000- PROS  Peds Endocrine Society has proposed new guidelines PUBERTAL DEVELOPMENT New guidelines propose that breast or pubic hair development should be evaluated only if  1 or both of these occur before age 7 in white girls or • Before age 6 in AA girls. Kaplowitz PB et al., Pediatrics 1999 Oct; 4:936-940
  • 16. 16 MENSTRUATION: What’s Normal? The REAL Answers, Evidence-Based Early cycles for adolescents are anovulatory and irregular – But not “anything goes” – Overall trend toward shorter and more regular cycles through adolescence Normal Menstrual Cycle length – Adolescents ~19-45 days – Adult women 21-38 days Amenorrhea defined as no periods for 90 days Bleeding 2-7 days Mean blood loss/cycle 30cc (20-60) – Chronic loss> 80cc associated with anemia
  • 17. 17 Vollman RF. The Menstrual Cycle. Major Problems in Obstetrics and Gynecology. Vol 7. Friedman EA, ed. W.B. Saunders Co., 1977. 31,645 cycles reported by 656 women
  • 18. MENSTRUAL NORMS IN ADULT WOMEN Fraser, I.S., et al., Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding? Hum Reprod, 2007. 22(3): p. 635-43.
  • 19. 19 MENOPAUSE--DEFINITION Cessation of Menses-FMP (final menstrual period) • X 1 year Average age 50-51 Ethnicity: • AA: 6-12 mos earlier than Caucasions ? • Mexicans: 1 year earlier than Caucasions • Japanese: 5 months later
  • 20. MENOPAUSAL TRANSITION  Increased variability of cycles transition to Long Cycles  Early age at menopause related to:  Smoking  Lower SES  Older age at menopause related to:  Longer cycles throughout reprod life  Longer more variable cycles prior to menopause  Higher parity  Use of COC
  • 21. DURATION OF MENOPAUSAL TRANSITION •Median age at entry is 45.5 •Marker for FMP •Onset of 90 day cycle •Earlier onset of 90 d cycle predicts earlier FMP •1-3 yrs from 90 d cycle to FMP •Median duration of the transition is 4.8 years •Range of 1-11 years Treloar, A.E., et al., Variation of the human menstrual cycle through reproductive life. Int J Fertil, 1967. 12: p. 77-126.
  • 22. The Stages of Reproductive Aging +10 staging system for reproductive aging in women 23
  • 23. 24 Randolph et al, JCEM 2011;96:746-54 FSH and FMP
  • 24. 25 PATTERNS OF MENOPAUSAL TRANSITION  Increasing variability followed by increasing cycle length-- ”typical”  “Just stopped”  History of long or irregular cycles  Increased variability and long cycles and then “revert” to prior, less variable pattern
  • 25. 26 Vollman RF. The Menstrual Cycle. Major Problems in Obstetrics and Gynecology. Vol 7. Friedman EA, ed. W.B. Saunders Co., 1977. 31,645 cycles reported by 656 women
  • 27. 28 • 16 yo girl • Primary amenorrhea • DDx: • Labs: CASE
  • 28. 29 • 16 yo girl • Primary amenorrhea • High FSH • High LH • Estradiol = • Etiology = • Therapy = CASE
  • 29. 30 • 16 yo girl • Primary amenorrhea • Low FSH • Low LH • Estradiol = • Etiologies = • Therapy = CASE
  • 30. 31 • 24 yo woman • Infrequent periods • Normal FSH • High LH • Estradiol = • Etiology = • Therapies = • Implications for future health = CASE
  • 31. 32 • 29 yo woman • Secondary amenorrhea • Elevated FSH • Elevated LH • Estradiol = • Etiology = • Therapy = CASE
  • 32. 33 • 45 yo woman • Infrequent periods • Elevated FSH • Estradiol = • Etiology = • Therapy = CASE
  • 33. 34 • 45 yo woman • LMP 13 months ago • Elevated FSH • Estradiol = • Etiology = • Therapy = CASE
  • 34. 35