Stages of Pubertal Development & Premenstrual Syndrome

DNB Paper Answer - Berek & Novak's Gynecology + ACOG 2023 Updates

PART 1: STAGES OF PUBERTAL DEVELOPMENT

Overview

Marshall-Tanner Staging

Breast Development (Thelarche)

Pubic Hair Development (Pubarche)

Sequence of Pubertal Events in Girls

1. Accelerated linear growth (first sign)
2. Thelarche (breast budding) - typically first recognized change
3. Adrenarche/Pubarche (pubic/axillary hair)
4. Peak height velocity
5. Menarche (average age ~12.5-13 years in the US; occurs approximately 2-3 years after thelarche)

Growth and Body Composition Changes

• Girls reach peak height velocity early in puberty, before menarche - so they have limited growth potential after menarche.
• Boys reach peak height velocity about 2 years later than girls.
• Boys grow an average of 28 cm during the growth spurt; girls grow a mean of 25 cm.
• Adult men are on average 13 cm taller than women.
• By maturity, men have 1.5x the lean body mass and 1.5x the skeletal mass of women; women have twice as much body fat.
• Estrogen drives characteristic fat distribution at thighs, buttocks, and abdomen in girls.
• Testosterone is the primary anabolic driver of male pubertal changes.

Mechanisms Underlying Puberty

1. Early puberty: Decreased sensitivity to the negative/inhibitory effects of low circulating sex steroids present in childhood
2. Late puberty: Maturation of the positive/stimulatory feedback response to estrogen, responsible for the ovulatory mid-cycle LH surge

• The central nervous system inhibits puberty onset until the appropriate time
• At puberty, the GnRH pulse generator is reactivated (disinhibited) - leading to increased amplitude and frequency of GnRH pulses
• Increased GnRH → increased gonadotropins → increased gonadal steroids

• Kisspeptin and Neurokinin B are implicated as gatekeepers for puberty onset
• Metabolic modifiers: Leptin and nesfatin-1 can alter the actions of these gatekeepers

Adrenarche

• Adrenarche refers to activation of the adrenal glands - the increase in adrenal androgen secretion (DHEA, DHEAS) that begins at ages 6-8 years
• Precedes and is independent of gonadarche (HPG axis activation)
• Responsible for early pubic and axillary hair, body odor, and early acne

Bone Age

• Bone/skeletal age is estimated from x-rays of the nondominant hand, knee, or elbow compared to standards (Greulich and Pyle atlas)
• Skeletal age correlates more closely with pubertal stage than with chronological age
• Used with height and chronological age to predict final adult height (Bayley-Pinneau tables)
• Midparental height formula: Add 13 cm to mother's height (for boys) or subtract 13 cm from father's height (for girls); average with other parent's height; ±8.5 cm gives the 3rd to 97th percentile range

Aberrations of Pubertal Development (Novak's Table 8-1)

• Most common cause: Constitutional Delay of Growth and Development (CDGD) - strong genetic component, represents an extreme of normal distribution
• Anatomic: Mullerian agenesis, imperforate hymen, transverse vaginal septum
• Hypergonadotropic (FSH >30 mIU/mL) hypogonadism: Turner syndrome, pure gonadal dysgenesis (46,XX or 46,XY)
• Hypogonadotropic (LH and FSH <10 mIU/mL) hypogonadism
• Also consider celiac disease, Crohn's disease, sickle cell anemia, cystic fibrosis

PART 2: PREMENSTRUAL SYNDROME (PMS) AND PMDD

Definition and Epidemiology

• PMS has been characterized by more than 100 different physical and psychological signs and symptoms, making it difficult to define scientifically
• The distinction from PMDD is important: PMDD is a more severe, psychiatrically defined disorder
• PMDD affects an estimated 3-5% of ovulating women
• Symptoms must be in the luteal phase and resolve with or shortly after onset of menses

Pathophysiology

• No specific serum hormone level is directly associated with premenstrual dysphoria
• A subgroup of women is vulnerable not to absolute hormone levels, but to hormonal changes (fluctuations in estrogen and progesterone)
• There is a correlation between the degree of hormonal change and incidence of mood disorder
• Serotonergic dysregulation is the leading hypothesis - abnormal CNS response to normal fluctuations of ovarian steroids, particularly progesterone metabolites (allopregnanolone) acting on GABA-A receptors

Diagnosis of PMDD (DSM-5 Criteria)

1. In the majority of menstrual cycles, at least 5 symptoms must be present during the premenstrual week
2. Symptoms start to improve within a few days after onset of menses
3. Symptoms become minimal or absent in the postmenstrual week

• Marked affective lability
• Marked irritability/anger/interpersonal conflict
• Marked depressed mood/hopelessness/self-deprecating thoughts
• Marked anxiety/tension

• Decreased interest in usual activities
• Difficulty in concentration
• Lethargy
• Marked change in appetite
• Hypersomnia or insomnia
• A sense of being overwhelmed or out of control
• Physical symptoms: bloating, breast tenderness

• Symptoms must markedly interfere with work, family, or academic responsibilities
• Must not be exacerbations of another existing disorder
• Must be corroborated by at least 2 months of prospective daily ratings
• Screen for domestic abuse and other contributing life circumstances

Treatment of PMS

• Elimination of caffeine from the diet
• Smoking cessation
• Regular exercise
• Regular meals with complex carbohydrates
• Adequate sleep
• Stress reduction (meditation, yoga, delegating responsibilities)

Treatment of PMDD (Novak's Table 23-2)

RECENT UPDATES: ACOG CLINICAL PRACTICE GUIDELINE No. 7 (December 2023)

Strong Recommendations

Conditional Recommendation

Key ACOG 2023 Points

1. SSRIs are first-line pharmacologic treatment for PMDD - supported by multiple RCTs. Both continuous daily dosing and luteal-phase dosing (days 14-28) are effective.
2. COC containing drospirenone (e.g., Yaz - EE 20 mcg + drospirenone 3 mg) has FDA approval for PMDD.
3. Multimodal approach is recommended - combining lifestyle, pharmacologic, and psychological interventions.
4. Diagnosis requires prospective symptom tracking - at least 2 months of daily ratings using validated tools (DRSP - Daily Record of Severity of Problems; PAF - Premenstrual Assessment Form).
5. GnRH agonists (with add-back estrogen-progestin) reserved for severe, refractory cases; add-back therapy required to prevent hypoestrogenic side effects.
6. Recommendations apply to both adults and adolescents (with caveats - limited specific evidence in adolescents).
7. Surgical management (bilateral oophorectomy): last resort for truly refractory cases; requires discussion of hormonal add-back therapy post-surgery.

Approach to Management (ACOG 2023 Stepwise)

Step 1: Confirm diagnosis with prospective symptom tracking x 2 months
Step 2: Lifestyle/behavioral interventions (exercise, diet, CBT)
Step 3: First-line pharmacologic → SSRIs ± COCs
Step 4: Second-line → GnRH agonists with add-back therapy
Step 5: Surgical (oophorectomy) - only for severe, refractory, definitive cases

Quick Mnemonics for DNB

• Berek & Novak's Gynecology, 16th Edition (ISBN 9781496380357) - Chapter 8 (Pediatric & Adolescent Gynecology, p. 311-327) and Chapter 23 (p. 1101-1103)
• ACOG CPG No. 7 (Dec 2023) - Management of Premenstrual Disorders, Obstet Gynecol 142(6):1516-1533

Collateral Blood Supply of the Uterus

DNB Paper Answer - Berek & Novak's Gynecology + Recent Updates

Primary Blood Supply of the Uterus

• Uterine artery - the dominant supply; arises from the anterior division of the internal iliac (hypogastric) artery
• Travels medially in the superior aspect of the broad ligament with a characteristic corkscrew/tortuous pattern (allows expansion in pregnancy)
• Crosses over the ureter approximately 1 cm lateral to the internal cervical os ("water under the bridge" - ureter = water, uterine artery = bridge)
• Blood flow through uterine arteries increases to approximately 500 mL/min in late pregnancy

Pelvic Blood Supply Diagram (Berek & Novak's Fig. 5-9)

Collateral Blood Supply of the Uterus

Principle of Pelvic Collateral Circulation

Table: Collateral Channels of Circulation in the Pelvis (Novak's Table 5-4)

Detailed Collateral Pathways

1. Ovarian Artery ↔ Uterine Artery (Most Important)

• The ovarian artery arises from the ventral surface of the abdominal aorta, just below the origin of the renal vessels
• It travels as part of the infundibulopelvic (suspensory) ligament into the broad ligament
• It anastomoses freely with the uterine artery in the mesosalpinx and broad ligament
• This bidirectional anastomosis provides the most important collateral channel to the uterus
• Clinical relevance: When the uterine artery is ligated (O'Leary stitch), blood supply is maintained via the ovarian artery; conversely in UAE, residual supply may come from ovarian artery branches

2. Superior Rectal Artery ↔ Middle Rectal Artery

• Superior rectal artery = terminal branch of the inferior mesenteric artery
• Middle rectal artery = branch of the internal iliac artery
• This anastomosis becomes active after internal iliac artery (IIA) ligation above the posterior division
• Provides indirect collateral to the uterus via cervical/vaginal branches

3. Lateral Sacral ↔ Median Sacral (Primary after IIA ligation)

• Lateral sacral arteries arise from the posterior division of the internal iliac
• They anastomose with the median sacral artery (a direct branch of the aorta)
• Burchell's studies (pelvic aortograms in 22 patients) demonstrated this is the first and main anastomosis activated after IIA ligation below the posterior division
• Provides important indirect collateral support

4. Iliolumbar Artery ↔ 4th Lumbar Artery

• Iliolumbar artery arises from the posterior division of the internal iliac
• Anastomoses with the 4th lumbar artery (from the aorta)
• This is the second most important anastomosis activated after IIA ligation
• Together with the lateral sacral/median sacral anastomosis, these are the two primary groups of collateral channels (Burchell's landmark contribution)

5. Deep Circumflex Iliac ↔ Superior Gluteal

• Deep circumflex iliac arises from the external iliac artery
• Anastomoses with superior gluteal and 4th lumbar artery branches
• Provides systemic-systemic collateral circulation

6. Vaginal Artery ↔ Uterine Artery

• The vaginal artery (branch of internal iliac, or sometimes directly from uterine artery) anastomoses with descending branches of the uterine artery
• Provides important collateral to the lower uterine segment and cervix

Anatomic Variation - An Important Surgical Caveat

• No constant order in which branches divide from the parent vessel
• Some branches may arise as common trunks or from other branches
• Obturator artery may arise from the external iliac or inferior epigastric artery
• Ovarian arteries may arise from the renal arteries or as a common trunk
• Inferior gluteal may originate from the posterior or anterior branch of internal iliac
• Blood flow patterns may be asymmetric from side to side

Clinical Surgical Applications

O'Leary Uterine Artery Ligation

• Bilateral ligation of uterine arteries at their origin from internal iliac (used in PPH)
• Reduces uterine blood flow by ~80%
• Blood supply maintained via ovarian artery anastomosis

Bilateral Internal Iliac (Hypogastric) Artery Ligation

• Reduces pulse pressure in pelvic vasculature by ~85%
• Converts arterial flow characteristics to venous (pressure reduction, not flow cessation)
• Collateral channels (lateral sacral/median sacral and iliolumbar/4th lumbar - Burchell's groups) allow continued pelvic perfusion
• Successful pregnancies reported after bilateral IIA + ovarian artery ligation
• Modern practice increasingly favors uterine artery embolization (UAE) or balloon occlusion over IIA ligation

Uterine Artery Embolization (UAE)

• Particle embolization via uterine arteries occludes fibroids' blood supply
• After UAE, collateral circulation (especially via ovarian artery) can re-establish uterine blood supply over time (relevant for UAE failure rates and fibroid recurrence)
• Bilateral UAE is needed because of collateral reconstitution

Recent Updates (2024-2025)

Burchell's Contribution (Historical but Exam-Important)

1. Lateral sacral arteries ↔ Median sacral artery
2. 4th lumbar artery ↔ Iliolumbar artery

Current Evidence on IIA Ligation (MDPI 2025 Review - Gynecology 2025;14(1):5)

• IIA ligation is increasingly replaced by selective arterial embolization and temporary balloon occlusion (preoperative or intraoperative)
• IIA ligation is rarely described in textbooks now - surgeons must be familiar with anatomy before attempting
• Complications include: buttock claudication, impotence, bladder and rectal necrosis (rare if collaterals are intact)
• No long-term consequences of properly performed IIA ligation - women have delivered normal infants subsequently (Creasy & Resnik's MFM)

After Uterine Artery Ligation (UAL)

Summary Table for Rapid Revision

• Berek & Novak's Gynecology, 16th Edition (ISBN 9781496380357) - Chapter 5 (Anatomy), pp. 161-167; General Principles No. 2, 3, 4; Table 5-4 Collateral Channels; Figure 5-9
• Imaging Anatomy Atlas Vol. 3 (ISBN 9781626239845) - Uterine Artery section
• Burchell RC - Pelvic vascular studies (historical landmark)
• IIA Ligation Review 2025 - Gynecology 2025;14(1):5
• Creasy & Resnik's Maternal-Fetal Medicine - Collateral circulation and PPH management