women repro

order of the phases

—Phases/ Events

—Menstruation

—Follicular Phase

—Ovulation

—Luteal Phase

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—Menstruation

—Marks the first day of a new menstrual cycle

—Discharge of bloody fluid containing endometrial and blood cells

—Typically lasts 3-5 days

—Triggered by decline in estrogen and progesterone (especially progesterone) from the last cycle

—Vasoconstriction causes endometrial tissue to die

—Uterine contractions cause it to be expelled

—The Early Follicular Phase

—Follicles contained in the ovaries are small

—Because of this, estradiol levels are very low

—Cervical mucus is dry

—The Late Follicular Phase

—The Late Follicular Phase

—Gradual rise in FSH stimulates the ovarian follicles

—Follicles compete with each other for dominance

—A dominant follicle (occasionally 2) will mature, becoming a fluid-filled Graafian follicle, which contains an ovum (egg)

—As follicles grow, they release more and more estradiol

—Estradiol stimulates the thickening of the endometrium (lining of the uterus)

—Estradiol also stimulates the cervix to produce increasing amounts of cervical mucus

ovulation

—Once estradiol levels reach a certain threshold, a surge of LH is triggered (related to the frequency of GnRH pulses)

—LH matures the egg and weakens the follicular wall, facilitating ovulation

—Once released, the ovum is swept up into the fallopian tube

—The Luteal Phase

—Corpus luteum: solid body formed after the ovum is released into the fallopian tube

—Produces significant amounts of progesterone, which is critical to making the endometrium receptive to implantation of a blastocyst (i.e. pre-embryo)

—High estradiol & progesterone inhibit FSH & LH

—High progesterone causes cervical mucus to dry up

—If ovum is not fertilized, corpus luteum disintegrates after 14ish days, resulting in a drop of estradiol and progesterone (resulting in menstruation)

Why is the Average Age of Menarche Declining???

—In the past:

—Improving living standards, nutrition

—More recent:

—Higher rates of obesity

—Exposure to endocrine-disrupting chemicals (https://www.endocrine.org/topics/edc)

—Greater exposure to light

—Consequences: increased risk of estrogen-dependent cancers

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How do I know when/ if I’m ovulating?

—Signs of ovulation

—Lots of “egg-white” cervical mucus followed by sudden drying up

—Increase in libido leading up to ovulation

—Ovarian pain during ovulation (also known as “mittelschmertz”)

—Mid-cycle increase in basal body temperature

—Period begins 12-15 days after suspected ovulation

—Note that in healthy women, about 10% of menstrual cycles are anovulatory (i.e. ovulation doesn’t occur)

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What about the Pill?

—Most birth control pills contain both synthetic estrogen and progesterone (called progestogen)

—Estrogen and progesterone feed back in the HPG axis to prevent FSH and LH release

—Result: no ovulation

—The progestogen also prevents the production of fertile cervical mucus

—During pill-free intervals, you experience withdrawal from estrogen and progestogen, resulting in bleeding

How do IUDs work?

—Both types of IUDs are inserted in the uterus

—The presence of an IUD in the uterus creates an inflammatory reaction that prevents fertilization of the ovum by sperm

—All phases of the menstrual cycle still occur

—Hormonal IUDs also release a progestogen, which prevents fertile cervical mucus and prevents thickening of the uterine lining

Why aren’t my periods regular?

—Occasional irregularity is nothing to worry about but chronically irregular periods is something to look into

—Possible causes of menstrual irregularity

—Stress can cause occasional irregularity

—Thyroid dysfunction

—Excessive exercise

—Eating disorders

—Uncontrolled diabetes

—Primary ovarian insufficiency

—Most common: polycystic ovarian syndrome

—

Polycystic Ovarian Syndrome (PCOS)

—5-10% of women

—Symptoms:

—2 out of 3 of the following criteria:

1.Menstrual irregularity

2.Signs of elevated testosterone (e.g. acne, excess body hair, hair loss)

3.Polycystic ovaries (via ultrasound)

—Responds well to low glycemic index diet & exercise

The History of PMS

—1931: Karen Horney writes a paper entitled “Premenstrual Tensions”

—1953: Dr. Katharina Dalton, British gynecologist, coined the term “premenstrual syndrome”

—Devoted her career to researching, writing about and treating PMS

—Believed PMS was due to deficient progesterone

—Estimated rate to be 30%

—Testified in over 50 trials in which the defendant had committed crimes in the premenstrual phase

—

—1931: Karen Horney writes a paper entitled “Premenstrual Tensions”

—1953: Dr. Katharina Dalton, British gynecologist, coined the term “premenstrual syndrome”

—1987: “Late luteal phase disorder” appears in the Appendix of the Diagnostic and Statistical Manual of Mental Disorders (DSM)

—2012: Premenstrual Dysphoric Disorder (PMDD) ‘upgrades’ to the front of the DSM

Inclusion of PMDD in the DSM:
 A Controversial Decision

ARGUMENTS AGAINST

Pathologizes normal variations in mood

Allows big pharma to re-patent old antidepressants for this new purpose

Encourages the depiction of women as highly emotional and irrational

Inclusion of PMDD in the DSM:
 A Controversial Decision

ARGUMENTS FOR

Existence is supported by a large body of research

Facilitates diagnosis, treatment, and research

Validates the experiences of many women

Quality of Life in PMDD

DSM-5 Criteria for PMDD

A. In most menstrual cycles, 5+ symptoms (at least one emotional symptom) present in the premenstrual phase and are absent in the week following menses.

1.Depressed mood, feelings of hopelessness or self-deprecating thoughts

2.Affective lability

3.Marked anxiety, tension, feelings of being “on edge”

4.Persistent anger, irritability, interpersonal conflicts

5.Decreased interest in usual activities

6.Difficulty concentrating

7.Lethargy, lack of energy

8.Changes in appetite, overeating or specific food cravings

9.Hypersomnia or insomnia

10.Feeling overwhelmed or out of control

11.Other physical symptoms such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of bloating or weight gain

●

DSM-5 Criteria for PMDD

A. In most menstrual cycles, 5+ symptoms (at least one affective symptom) present in the premenstrual phase and are absent in the week following menses.

B. Symptoms impair work, interpersonal or social function.

C. Not merely a premenstrual exacerbation of another disorder.

D. Confirmed via prospective daily ratings for 2 consecutive cycles.

Interpreting Daily ratings

—For a diagnosis of PMDD:

—At least 5 symptoms (including 1 core) increase in severity by at least 30% from the premenstrual week to the postmenstrual week (days 4-10)

—Ratings must be at least in the “moderate” range during the premenstrual week

—Ratings must be no higher than “mild” in the postmenstrual week

PMDD Assessment:
Why Prospective Ratings are Critical

—A woman needs to track her symptoms daily for two menstrual cycles and have symptoms in the late luteal phase that resolve with the onset of menstruation

—Is this really necessary?

—Yes! About 60% of the time, retrospective reports of premenstrual symptoms don’t match prospective tracking

—Unfortunately, clinicians only use prospective tracking 12% of the time

PMDD Prevalence

—Strict DSM-5 diagnosis

—1-2%¹

—Clinically significant but sub-threshold symptoms:

—13-19%²

—E.g. <5 symptoms

Prevalence of PMDD Symptoms

Suicidality & PMDD

The Argument For Including Suicidality in the DSM

—Seems to be highly prevalent in those with PMDD

—Would encourage clinicians to assess suicidal risk

—Identify the need for intervention

—Would prevent misdiagnosis of other conditions in which suicidality is listed (major depression, bipolar, borderline personality disorder)

The Argument Against Including Suicidality in PMDD

—Limitations of current research

—Not prospectively-confirmed PMDD

—Suicidality not tracked across the cycle

—Questions to be answered

—What is the prevalence of suicidality in prospectively-confirmed PMDD?

—Does it follow the same on-off pattern as other PMDD symptoms?

—How is the prevalence of PMDD affected by including it?

—What is the clinical utility of adding it? Does it lead to improved diagnosis and treatment?

PMDD Subtypes?

PMDD Subtypes

—Onset of symptoms could occur:

—At the start of the luteal phase

—One week into the luteal phase

—Offset of symptoms could occur:

—At the start of the follicular phase

—One week into the follicular phase

—Suggests the neurobiological effects of hormones may be delayed or slow to resolve in some women

—Also, prominent symptoms may differ from person to person or cycle to cycle

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PMDD & Hormonal Levels

—One thing that these researchers have pretty clearly established so far: women with PMDD do not have abnormal hormone levels

—Estradiol

—Progesterone

—LH, FSH

—Sex hormone binding globulin

—Instead, it’s thought that PMDD is an abnormal response to normal hormonal changes

Leuprolide Study: Part 1

—20 women with PMS (age 21-45)

—Confirmed with prospective mood ratings for 3 consecutive cycles showing 30%+ increase in symptoms during premenstrual phase

—Randomly assigned to receive 3 monthly injections of

—Leuprolide acetate (GnRH agonist) OR

—Saline placebo

—PMS symptoms rated daily using a visual analog scale and Daily Rating Form

—Blood samples drawn every 2 weeks

What is Leuprolide?

Results

—A GnRH agonist

—Results in a big increase in estrogen in the short-term

—High estrogen feeds back to shut down the axis

—Result: HPG axis shutdown

—At baseline (before receiving either Leuprolide or placebo), both groups show an increase in symptoms during the premenstrual phase

—After treatment, only the placebo group shows an increase in symptoms during the premenstrual phase

—Conclusion: no reproductive hormones = no PMS