Endometrial Ablation

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Here’s your RoshReview Question of the Week!

A 41-year-old G3P2103 woman is scheduled to undergo nonresectoscopic endometrial ablation for a history of heavy menstrual bleeding. She previously tried combined oral contraceptives but was not satisfied with medical management. An endometrial biopsy was completed and benign. Which of the following do you inform her is the most common complication when counseling her about the risks of the procedure?

Check to see if your answer is correct at the links above!

Read along with ACOG PB 81

What is an Endometrial Ablation? 

  • History and Rationale 

    • Minimally invasive surgical procedure designed to treat heavy uterine bleeding in select women who DO NOT WANT FUTURE FERTILITY 

    • Developed originally in 1937 

      • 1967 - cryoendometrial ablation where you “supercooled” the endometrial lining

      • Becomes more prevalent in the 1980s when hysteroscopy became more widely available 

  • How is it done today? - many ways! 

    • Laser and resectoscopic endometrial ablation 

      • Done under hysteroscopic visualization 

      • Uses a resectoscope with 4 current techniques 

        • Endometrial desiccation with electrosurgical rollerball or rollerbarrel - basically heats the tissue up to 60-90 degrees and destroys the endometrium 

        • Resection with monopolar or bipolar loop electrode - will also resect endometrium to level of myometrium (basically same way that we take care of fibroids from within)  

        • Radiofrequency vaporization - high energy to rapidly heat the intracellular water to 100 degrees C → vaporization of tissue, but no tissue is removed 

        • Laser vaporization - same as above 

    • Nonresectoscopic techniques (in the US) - can be nice because these can sometimes be less uncomfortable and can be performed in the office 

      • Bipolar radiofrequency (Novasure) - 3-dimensional bipolar mesh probe that delivers radiofrequency current until specific tissue impedance is reached 

      • Cryotherapy (Her Option, Cerene) - probe inserted into the uterus and cooled via liquid nitrogen or differential gas exchange 

      • Circulating hot water (Hydro ThermAblator or HTA-ablation) - only one of the non-resectoscopic techniques that uses hysteroscopy.

        • Sheath is inserted into the uterus → heated saline is administered for 10 minutes, and fluid should be at 90 degrees C

      • Combined thermal and bipolar frequency (Minerva) 

        • Heat applied to endometrium via silicone membrane with circulating ionized argon gas (advertised as “plasma”) 

      • Vapor ablation (Mara) - no longer FDA approved 

    • After the endometrium is burned, it can scar down, leading to difficulty entering the uterine cavity again 

    • Anesthesia 

      • Most trials describing non-resectoscopic ablation devices have used local anesthesia and parenteral conscious sedation

      • Can use cervical and paracervical block if desired to do procedures in the office - however need to select if patient is a good candidate for in office procedure (ie. low risk for complications) 

Candidacy for Endometrial Ablation  

  • Who is the right candidate? 

    • Treatment is indicated for heavy bleeding in premenopausal women with no desire for future fertility 

      • An important caveat: this should be for those with heavy OVULATORY menstrual bleeding 

      • Should not be first line to treat for abnormal uterine bleeding due to anovulation 

        • This is because you should figure out the cause of that abnormal bleeding otherwise and treat the cause (ie. if due to PCOS, treat for PCOS) 

        • That is not to say that a patient with PCOS cannot have an ablation - however, you need to make sure that you are treating the causes of the PCOS.

    • Usually, these are patients who have tried other medical therapies and have failed or who should not have medical therapies

    • It is importance to counsel that patients should accept normalization of menstruation, not complete amenorrhea 

      • Not a treatment for those who do not want to have menstruation 

      • Variability across studies in amount of menstrual bleeding after ablation

      • In a meta-analysis, both non-resectoscopic and resectoscopic ablation resulted in similar rates of amenorrhea at 1 year (37% vs 38%) 

Preoperative Evaluation

  • Evaluate the structure and histology of the endometrial cavity 

  • Reasons:

    • Rule out cancer - either via hysteroscopy or endometrial biopsy in the office

      • Don’t want the reason for heavy bleeding to be cancer and complete endometrial ablation which can scar the endometrium and make later evaluation very difficult  

      • Those with hyperplasia (EIN) or cancer should not undergo ablation 

    •  Evaluate the shape of the uterine cavity 

      • Can be done either via sounding + transvaginal ultrasound, sonohysterogram, hysteroscopy, or combination 

      • Evaluate internal architecture (ie. is there a bicornuate uterus? Are there fibroids?)

      • Reason is that many of the devices have uterine cavity requirements.

        • For example, for Novasure, the cavity must sound between 6-10cm and have a cornua to cornua distance of at least 2.5cm. Also, those with polyps or fibroids > 2cm were excluded from the FDA approval studies 

  • Pretreatment 

    • Not required, but most surgeons will usually use hormonal agents to pre-treat to thin the endometrium 

    • GnRH agonist can be used 30-60 days prior to procedure 

  • Risk counseling

    • There are many adverse events that have been reported from ablation and can depend on the device used:

  • Some rare but possible complications: 

    • Distention media overload - just like in hysteroscopy.

      • Especially if you are doing resectoscope and you are using monopolar instruments, you have to use electrolyte-free fluid like 3% sorbitol or 5% mannitol - review our hysteroscopy episode with Dr. Dolinko to learn more! 

    • Uterine trauma - as with any procedure in the uterus, there is possibility of injury. Specifically, with ablation, injury is usually caused when there is hemorrhage or perforation.

      • Cervical lacerations and vaginal burns can also occur if hot fluid comes out through the cervix  

    • Postablation tubal ligation syndrome

      • Can occur in patients with history of tubal ligation 

      • Described as cyclic pelvic pain, likely due to residual and trapped endometrium in one or both cornua - tissue cannot exit through the cervix or through the cornua due to ablation causing scar tissue + tubal ligation causes scar tissue 

      • Incidence has been reported as high as 10%  

  • Complications that are more significant 

    • Pregnancy 

      • Ablation is not designed to be a form of birth control. Patients should be counseled extensively that they should not get pregnant and use a form of reliable birth control afterward 

      • Pregnancy can still occur after ablation 

        • Those that continue pregnancy have higher rates of malpresentation, prematurity, placenta accreta, and perinatal mortality 

    • Endometrial malignancy 

      • Endometrial ablation does not seem to delay the diagnosis of malignancy 

      • However, due to scarring of the endometrium, it can make it more difficult for usual assessment of the endometrial tissue such as biopsy or hysteroscopy 

      • In one study of 303 patients who needed endometrial sampling after ablation, the failure rate for obtaining bleeding assessment was 40% 

Contraindications to Endometrial Ablation

  • Uterine size/shape - as discussed before; all available non-resectoscopic endometrial ablation devices have limitations with respect to size of cavity and extent of anatomic distortion 

  • Do not perform if:

    • Pregnant or recently pregnant or desires future pregnancy 

    • Presence of active or recent uterine infection 

    • Endometrial malignancy or EIN 

  • Consider not performing if: 

    • Uterine anomalies - ie septum or unicornuate uterus 

    • Myometrial thinning after uterine surgery 

    • Postmenopausal women - very few studies on postmenopausal women, and those are usually small; the studies were done in those with persistent bleeding after using HRT 

Outcomes from endometrial ablation

  • Overall outcomes 

    • Non-resectoscopic and resectoscopic ablation result in comparable rates of amenorrhea and patient satisfaction 

    • However, resectoscopic ablation is associated with more OR time, more frequent use of GA, increased risk of surgical complication (ie. fluid overload) 

    • Resectoscopic procedures are less costly

      • Resectoscopic procedures: $125-$150 

      • Non-resectoscopic: $850-$1300  

  • Improvement in bleeding 

    • Patients may have irregular bleeding immediately following procedure 

    • Success rates should not be determined until 8-12 weeks after surgery 

    • Randomized trial of Her Option cryo vs. resectoscope (279 patients): comparable rates of menstrual reduction at 1 year (85 vs. 89%) 

    • Patient satisfaction overall is high for both types of ablation (91 vs 88%) at one year, and similarly at 2-5 years (93 vs 87%) 

  • Surgical outcomes 

    • Subsequent surgery rates range from 17-25% for both types 

    • Hysterectomy rates are 14 vs 19% 

    • Higher risk of treatment failure in younger patients (<45 years old): 

      • Risk of subsequent hysterectomy or repeat ablation was 2x in patients <45 years old compared to patients >45 years old 

#MedEd: An Interview with Dr. Adam Rosh

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On today’s #MedEd Wednesday series, we interview Dr. Adam Rosh. Dr. Rosh is the founder of RoshReview, an online question-bank review company covering a number of subject areas, including the NBME shelf exams, CREOGs, and written ABOG boards!

Prior to being involved in test prep, Dr. Rosh spent time in academic medicine, even serving as an EM residency program director in Detroit, MI. He shares some of his experiences, his best test prep advice, and career advice with us today.

Osteoporosis: An Update

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Here’s the RoshReview Question of the Week!

A 53-year-old postmenopausal woman has a BMI of 19 kg/m². She is a chronic smoker and is taking steroids for rheumatoid arthritis. She drinks four alcoholic beverages per day. Her T score is −2.1. What can be a side effect of the recommended medication for her?

Check to see if your answer is right at the links above!

One of our first episodes from December 2018 was about osteoporosis, referencing the now withdrawn ACOG PB 129. ACOG has made a major change in its clinical practice documents that you’ll notice going forward – for future publications, Practice Bulletins will now have the new name change to “Clinical Practice Guidelines,” reflecting their main purpose as guideline documents. 

Committee Opinions will be split into two groups, known as “Clinical Consensus” and “Committee Statement” documents. There are also the categories of “Practice Advisories” and “Obstetric Care Consensus” documents.

ACOG’s new guideline nomenclature!

The first Practice Bulletin to get the CPG treatment is Osteoporosis. So let’s review CPG #1!  

Background

  • Osteoporosis is a generalized loss of bone mass and decline in bone quality, leading to increased fracture risk.

    • 8.2 million women >50 years old have osteoporosis (compared to 2 million men)

    • 71% of fractures in osteoporotic persons occur in women

      • 50% of women over 50 will have an osteoporotic fracture

    • Additional 27.3 million women have low bone mineral density (formerly known as “osteopenia”)

      • Unfortunately, only 24% of women aged 60 and older receive osteoporosis treatment in the year after a fracture.

  • Risk factors aside from female sex:

    • Age: as described above, particularly over age 50

    • BMI under 20 or body weight less than 127 lb

    • Smoking

    • Alcohol use (especially more than 3 drinks daily)

    • Parental history of hip/spine fracture

    • Conditions, disease, and medications associated with “secondary osteoporosis”

      • HIV/AIDS and antiretroviral drugs

      • Anorexia

      • Diabetes mellitus (T1 and T2)

      • Gastric bypass

      • Hyperparathyroidism

      • POI / premature menopause / Turner syndrome or use of Aromatase inhibitors, GnRH agonists, DMPA

      • Antiepileptic drugs

      • Chronic steroid use

      • And more!

    • Racial variation: white and Hispanic populations with highest fracture risk

      • However, Black patients and Hispanic patients are less likely than White patients to get DXA screening after a hip fracture and less likely to receive osteoporosis treatment when indicated.

      • Black women also have higher rates of 1 year mortality, destitution, and other major adverse events following a fracture compared to White patients.

      • Varying studies looking at this have suggested multifactorial reasons for this inequity, including healthcare practitioner bias, patient mistrust of the healthcare system, other social determinants of health, or some complex interplay of these factors.

  • Bone physiology

    • 90% of bone mass is acquired during childhood and adolescence. Peak bone mass in adolescence has been correlated with later-life fracture risk! 

    • Bone mineralization and buildup in puberty is modified and optimized by sex steroids, predominantly estrogen, in both young girls and boys. Peak density is achieved around age 19 in women, and 20.5 in men. 

    • In adulthood, bone is comparatively in physiologic equilibrium -- the formation of new bone (facilitated by osteoblasts) comes at a rate equal to, or slightly surpassed by, bone resorption (facilitated by osteoclasts). 

      • Over time, this begins to favor resorption more and more, and is part of aging. 

    • The loss of estrogen seen in menopause triggers a time-limited rapid bone loss in women that is not seen in men, and there are countering views on whether this is a pathologic or physiologic process. 

      • Age also plays a factor – an 80 year old patient is at much higher risk for fracture than a 50 year old patient with the same BMD.

  • Prevention strategies

    • In young patients, part of our well-patient counseling should be on prevention of osteoporosis.

    • Prevention boils down to physical activity and calcium/vitamin D supplementation

    • Activity

      • ACOG recommends routine aerobic physical activity and weight bearing exercise to maintain bone health and prevent bone loss.

        • Recommendation of CDC for 150-300 minutes/wk of moderate intensity, or 75-150 mins/wk of vigorous activity aerobic exercise (or some combination) advised.

        • Weight bearing exercises appear to show most benefit – specifically mentioned are free weights, resistance bands, jogging, stepping, and jump rope.

        • Advises that patients in menopausal transition and in menopause are intentional with exercise, as weight-bearing, high force exercise or high-intensity interval training (HIIT)-style exercise have demonstrated small but significant increases in BMD.

        • Tai chi in postmenopausal women gets special mention in improving balance, preventing falls, and may have beneficial effect on BMD and bone turnover.

    • Calcium and Vitamin D

      • ACOG recommends consumption of appropriate amounts of these nutrients

        • Calcium:

          • Age 19-50: 1000 mg

          • Age 50+: 1200mg 

        • Vitamin D: 

          • Up to 70: 600 IU

          • After age 70: 800 IU

          • Patients wth history of vitamin D deficiency may need additional

          • USPSTF and Endocrine Society do not recommend screening for vitamin D deficiency in asymptomatic adults (i.e., routine screening)

Diagnosis

  • Don’t just jump to your DXA! And to know who might benefit, an H&P are essential.

    • Height loss can be an indicator of asymptomatic vertebral fracture – consider doing vertebral imaging by Xray or DXA if:

      • a 0.8in (2cm) loss in height over 1-3 years, or 

      • a loss of 1.5 in (4cm) since peak height at age 20

    • Risk assessment tools can identify patients who may benefit from screening, the most common of which is the FRAX score

      • This tool is useful to identify patients prior to a DXA who may be at high risk of fracture, and to identify patients after a DXA who may benefit from osteoporosis treatment (more on that later)

    • Recommendations for when to get a DXA:

      • DXA is recommended universally in women 65 or older

      • DXA is recommended prior to age 65 in postmenopausal patients who have a pre-DXA FRAX score indicating an 8.4% or greater risk of major osteoorotic fracture in the next 10 years – 

        • This is equivalent to the 10-year risk of a 65-year old White woman without risk.

        • ***NOTE*** this is lower than previous recommendation, which was 9.3%

      • Finally, ACOG suggests repeat DXA only in patients with initial testing near treatment thresholds, or if risk factors change significantly (i.e., started new glucocorticoid therapy). 

        • Generally, this will be no sooner than 2 years after an initial screen.

        • For those of average risk, there is no consensus on whether or when repeat DXA should be performed.

  • Osteoporosis and low BMD are diagnosed using dual energy X-ray absorptiometry (DXA).

    • Osteoporosis is defined as a T-score of < - 2.5 standard deviations

    • Low BMD is defined as a T-score of -1 to - 2.5 standard deviations

      • The T-score is calculated by looking at an individual’s BMD measurements at hip or spine, compared to a mean for a healthy, young-adult reference population.

      • DXA will also report a Z-score, which compares an individual’s BMD versus the mean of the patient’s same age, sex, and ethnicity. 

        • ACOG notes that further research is needed to explore the contributors to T and Z score differences based on race/ethnicity. 

    • Osteoporosis can also be diagnosed by:

      • A history of a fragility fracture, including an asymptomatic vertebral fracture

      • A T score consistent with low BMD, and an increased risk of fracture as determined by a risk assessment tool such as the FRAX scale

        • Specifically,  a >20% risk of major fracture, or >3% risk of hip fracture, in the next 10 years.

Treatment: Fall Prevention

  • ACOG spends  a significant part of this document asking OB/GYNs to assess fall risk in patients with low BMD or osteoporosis. 

    • Identifying impairments in mobility, medical conditions or medications that may sedate or impair balance or gait; environmental factors in the home (i.e., loose throw rugs, poor lighting) is imperative for fall risk

    • Also encouraging patients, particularly seniors, to engage in exercise to help reduce risk as we mentioned before!

  • Unlike in the old Practice Bulletin, the new CPG doesn’t focus on the treatment of osteoporosis. This likely reflects the fact that most OB/GYNs do not treat osteoporosis primarily – worth referring to endocrinology to prescribe and monitor these therapies.

  • However, familiarity is good to have, so here’s a few pointers from our previous podcast!

    • Bisphosphonates: suffix of -dronate. Demonstrated efficacy of reducing fracture risk 35-65%. Often limited therapy less than 5 years due to limited data on use beyond then. Weird side effects -- significant reflux or esophageal trauma (stand upright 30-60mins after taking med), osteonecrosis of the jaw -- these are fortunately rare, but testable. 

  • Raloxifene: a SERM, has agonist effects on the bone and antagonist effects on breast and uterus, so good choice in patient with (risks of ) breast CA/uterine CA, with concomitant osteoporosis. Big side effect consideration is VTE -- consider carefully in someone with a history of stroke/PE/DVT. 

  • Calcitonin, Denosumab, recombinant PTH: other options but not worth your time – you’ll be referring to an endocrinologist to consider that

  • Hormone Replacement Therapy (HRT): not approved for primary treatment of osteoporosis, but has been shown to reduce risk of fracture in peri/postmenopausal women by 33-36%, based on the WHI study. A reasonable adjunct to have for patients with low BMD and no other considerations/contraindications. We covered HRT a long time ago as well in this podcast with Dr. Eger!

Vulvar Intraepithelial Neoplasia (VIN)

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Here’s the RoshReview Question of the Week!

A 41-year-old woman, G2P2, presents to your office for postcoital bleeding. She has a history of laparoscopic hysterectomy for persistent cervical intraepithelial neoplasia 3. A vaginoscopy is performed and shows multiple lesions in the upper third of the vagina. One lesion located within a suture recess near the vaginal cuff is not able to be visualized in its entirety. Biopsy reveals a high-grade squamous epithelial lesion. Her social history is significant for smoking. Which of the following is the best therapy?

Check your answer at the links above and check out RoshReview’s CREOG question bank!

Follow along with ACOG CO 675!

What is Vulvar Squamous Intraepithelial Lesions (SIL) and why do we care? - previously called VIN 

  • VIN is increasingly common - esp in women in their 40s 

    • VIN has increased more than 4x from 1973 to 2000! 

    • VIN should be considered a premalignant condition

  • How do we classify?

    • Has changed a lot over time, but most recently we have used:

      • LSIL of the vulva - used for low grade changes that come from HPV infections (usually present as genital warts) 

      • HSIL of the vulva - used for high grade changes that comes from HPV infections (precancerous lesions) - used to be called “usual type” 

        • VIN, warty type 

        • VIN, basaloid type 

        • VIN, mixed (warty or basaloid) type 

      • Differentiated type - from things like lichen sclerosus 

    • The International Society for the Study of Vulvovaginal Disease ISSVD recommends these terms to unify the nomenclature of HPV-associated squamous lesions of the lower genital tract - all of these are based on histopathologic findings:

ACOG CO 675

How do we diagnose VIN? 

  • Unfortunately, no good screening strategies

    • Detection usually limited to visual inspection 

    • What does it look like?

      • Can vary. Most will be raised, but some can be flat 

      • Discoloration of the skin - white, gray, red, brown, or even black 

    •  Should biopsy to make definitive diagnosis if not sure of diagnosis of something else (ie. LS) 

      • Biopsy should be performed in postmenopausal women with apparent genital warts and in women of all ages with genital warts where topical therapies have failed 

      • Colpo can also be useful - just remember that you need to soak the vulva in acetic acid with a gauze pad for several minutes 

What do we do to treat? 

  • Treat all vulvar HSIL (VIN usual type) 

    • Surgery 

      • Wide local excision should be done if there is suspected to be cancer 

      • Can be occult invasion even if initial biopsy is vulvar HSIL 

      • Should include gross margin of 0.5-1 cm around tissue with visible disease 

      • May be altered to avoid injury to critical structures like clitoris, urethra, anus, or other structures 

      • However, if lesions in critical areas, should be referred to specialist to avoid impaired psychosexual function (ie. if extensive around the perineum, reaching back to anus or around the clitoris 

      • If clear margins in excised tissue, much lower risk of recurrence 

    • Laser Ablation Therapy 

      • Should be done if occult invasion is not a concern

      • Can be used for single, multifocal, or confluent lesions, although risk of recurrence may be higher than with excision 

      • Colpo can help delineate lesions of margins 

      • As with excision, 0.5-1cm margin to be treated 

      • Remember than unlike genital warts, the entire thickness of the epithelium must be treated

    • Medical Therapy 

      • Topical imiquimod 5% 

      • Regimens that have been published include 3x/week to affected area for 12-20 weeks 

      • Colpo assessment at 4-6 weeks 

      • Residual lesions require surgical treatment 

  • Surveillance

    • Recurrence rate is as high as 9-50% with all treatment regimens

      • Higher with positive margins

      • Lower in surgically treated patients 

    •  Follow up has been limited in most studies 

    • However, women with Vulvar HSIL are at high risk of recurrence during their life time 

    • If complete response to therapy and no new lesions at follow-up visits, scheduled 6 and 12 months after initial treatment should be monitored by visual inspection 

Puberty and Precocious Puberty

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Here’s the RoshReview Question of the Week!

A 30-year-old woman brings her 7-year-old daughter for consultation. She noted the presence of clinical signs of puberty and is worried that this might be occurring too early for her age. Which of the following distinguishes central precocious puberty from peripheral precocity?

Check your answer by clicking the links above!

What is puberty? 

  • Physical process of maturation from child to adult that is capable of sexual reproduction 

  • Also process of cognitive and psychosocial maturation

  • Two main areas: 

    • Gonadarche - activation of the gonads by pituitary hormones (FSH/LH) 

    • Adrenarche - increase in production of androgens in the adrenal cortex 

  • Cause

    • Triggered by hypothalamic activation and production of GnRH in pulsatile fashion that leads to FSH and LH production 

    • Not completely understood what causes the hypothalamus to begin this process

      • Thought to be governed by many factors like general health, nutrition, genetic factors, and other environmental cues 

      • Interesting to think about since the age of menarche in Europe decreased from 17.5 to 12.5-13 years in the last few centuries 

  • Timing of puberty

    • On average, girls begin puberty at age 10-11

  • One other note 

    • Puberty can be a time of emotional distress 

    • Not only are patients usually preteens or teens, with multiple societal and home pressures (school, friends, parents, etc), they are also experiencing significant changes in their bodies 

    • Child psych studies have shown that clinical symptomatology for previously diagnosed psychiatric disorders increase steeply when they reach puberty, and for some, this is the first onset of psychological symptoms 

    • So for these patients, important to follow them and work closely with your peds colleagues 

What are the different components of puberty? 

Mnemonic: boobs, pubes, spurt, squirt - Defined by Marshall and Tanner in 1970 (yes, that Tanner!) 

  • Thelarche - breast development 

    • Usually first physical sign of puberty is breast buds 

  • Pubarche (adrenarche?) - growth of pubic hair, usually follows a few months after breast development begins 

    • Thelarche and pubarche form the basis for Tanner staging in girls: (image source)

  • Growth spurt  

  • Menarche - getting your first period; the average age in the US is around age 12

So what is precocious puberty? 

  • More on timing of puberty:

    • Usually, puberty begins around the age of 10

      • However, there is a wide range, and can be anywhere from age of 8-13. Remember, puberty is NOT just beginning of menstruation! 

      • It can be evidence of breast development, pubic hair growth, etc.  

    • Precocious puberty is evidence of puberty that starts 2.5 SD earlier than the populational norm

      • Classically, it’s been defined as breast budding before the age of 8 in girls, though there is some racial differences in the literature that range somewhere between the ages of 7-8, and there is an increasing trend of earlier puberty in the US.

      • For simplicity’s sake, we will use the age of 8 as our cut off – at least when we should start THINKING that there maybe signs of precocious puberty 

  • Incidence and Risks

    • This is a little difficult to assess 

      • You might expect it to be 2% because we are using 2 to 2.5 standard deviations from the general population in the US 

      • But… in a population-based study, breast and/or pubic hair development at age 8 occurred in 48% of Black females and 15% of white females in the US. At age 7, this was 27% and 7% 

      • But if you look at a different population, the results are drastically different 

      • So… definition of precocious puberty is overall problematic, especially in female children. Instead, need to take into other factors as well, such as obesity

  • Strong predominance for females (approximately 87% of those evaluated in one study) 

  • In about 80% of girls with precocious puberty, it will be idiopathic 

Why do we care about precocious puberty? 

  •  Psychosocial reasons

    • Early menarche is often associated with earlier timing of sexual debut 

    • Increased risk of teenage pregnancy and sexually transmitted infections (HPV) 

    • Children may not be prepared for the implications of puberty and sexual maturation 

  • Other implications/health 

    • Early closing of the epiphyseal plates can lead to shorter stature 

    • Increased risk of breast cancer, heart disease, diabetes, and all-cause mortality 

What causes precocious puberty? 

  • Central precocious puberty (CPP)

    • Definition: Early maturation of the HPO axis … what causes it? 

    • Idiopathic 

      • In about 80-90% of females, but only 25% of males 

    • Central nervous system lesions

      • Hypothalamic hamartomas 

      • Other CNS tumors 

      • Cranial radiation 

  • Peripheral precocity 

    • Usuall due to excess secretion of sex hormone 

    • Ovarian tumors - overall rare, but can be from granulosa cell tumors. Rarely, sertoli/Leydig cell tumors can cause androgenization 

    • Primary hypothyroidism 

      • Severe, long-standing hypothyroidism can occasional cause precocious puberty 

      • Thought is due to cross-reactivity and stimulation of FSH receptor by high levels of TSH (same alpha sub unit) 

    • Exogenous chemicals/sex steroids  

    • Adrenal tumors 

    • Congenital adrenal hyperplasia - though these patients may present as early as infancy 

    • McCune-Albright Syndrome

      • Super rare → triad of peripheral precocious puberty, irregular cafe-au-lait spots (coast of Maine), and fibrous dysplasia of the bone  

How do we work this up? 

  • As always, history and physical 

    • If you suspect, you should ask patient and guardian 

    • When did they first notice changes, and how long has this been going on for? 

    • How quickly has this been progressing? 

      • Has this been occurring in the last year, and there has been very quick development of breast tissue with rapid onset of menstruation? More concern for peripheral source or tumor 

      • What about growth? Rapid growth may suggest CPP. Slower growth might signal benign or idiopathic cause 

    • Any changes with headaches, vision changes (suggests CNS tumor) 

    • Possible exposure to exogenous chemicals? Is mom on hormone replacement therapy and using estrace gel or cream? Did the child somehow get into it? 

    • Physical exam 

      • Height, weight, and height velocity (not something we usually do, so this might be best evaluated by the patient’s pediatrician!) 

      • Look for signs of McCune Albright - are there cafe au lait spots? 

      • Pubertal staging (Tanner Staging) 

  • Testing to order 

    • Bone radiograph - we don’t generally do this, so maybe think of referring to pediatric endocrinology, especially for follow up

      • Usually a hand X-ray to look at the growth plates in the metacarpals, wrist, etc 

      • Can assess for advance in bone age or premature closure of the growth plates 

    • FSH, LH, estradiol, and testosterone 

      • Elevated estradiol with suppression of FSH or LH is suggestive of peripheral production 

    • Consider getting a brain MRI to r/o central lesion 

    • Pelvic ultrasound - this will allow us to see peripheral tumors 

    • Specifically in patients with precocious pubarche (ie. pubic hair growth, axillary hair growth, but no menarche) 

      • Measurement of adrenal steroids 

      • Early morning 17-OHP, DHEA, testosterone, androstenedione 

  • Also refer to pediatric endocrinology! 

  • Treatment is based off of the cause - which we won’t cover today, but:

    • Principles of treatment will be based off of child’s age, rate of progression, height velocity, estimated height 

    • Goal of treatment is to allow child to grow to normal adult height and also to relieve psychosocial stress 

    • Usually for children with CPP, can treat with GnRH agonist 

    • Again - usually this is done with pediatric endocrinology, so we will defer further management to them.

      • This episode is designed to help you figure out the initial stages if someone comes to you with this issue!