Emergency Contraception: What’s your Best Option?

BACKGROUND AND PURPOSE:

  • Shen et al. (Cochrane Review, 2017) sought to determine which emergency contraceptive method is the most effective, safe and convenient to prevent pregnancy

METHODS:

  • Systematic review and meta-analysis
  • Pooled data from different databases and literature
  • Primary outcome was observed number of pregnancies
  • Secondary review outcomes were side effects and changes in menses

RESULTS:

  • 115 trials with 60,479 women were included
  • Pharmacologic emergency contraceptives were ranked as follows (from most to least effective)
    • Mifepristone
      • Mid-dose mifepristone (25 mg to 50 mg) associated with fewer pregnancies than low-dose (less than 25 mg)
    • Ulipristal acetate (a selective progesterone receptor modulator)
    • Levonorgestrel
      • Inconclusive whether single-dose levonorgestrel (1.5 mg) or two-dose regimen (0.75 mg 12 hours apart) is superior
    • Yuzpe method (estradiol-levonorgestrel combination)
  • No statistical difference identified between Cu-IUD and mifepristone
  • Nausea and vomiting
    • Yuzpe > Mifepristone
    • Yuzpe > Levonorgestrel
  • Menstrual irregularities
    • Ulipristal acetate users are more likely than levonorgestrel to have delayed menstruation
    • Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related
  • Obesity: The authors cite results from Jatlaoui and Curtis (Contraception, 2016) systematic review
    • Levonorgestrel
      • 4-fold increase risk of pregnancy in obese women (BMI ≥ 30 kg/m2) compared to BMI ≤ 25 kg/m2
      • At weight of 80 kg, pregnancy rate > 6% which is the same as probability without contraception
      • At weight < 75 kg, rate of pregnancy < 2%
    • Ulipristal acetate
      • 2-fold increase risk of pregnancy in obese women (BMI ≥ 30 kg/m2) compared to BMI <30 kg/m2 but CIs wide and did not reach statistical significance
    • However, other analyses did not demonstrate consistent association when adjusting for other covariates

CONCLUSION:

  • Levonorgestrel and mid-dose mifepristone were more effective than Yuzpe with fewer side effects
  • Cu-IUD is the most effective emergency contraceptive along with mifepristone and the only method that will provide ongoing contraception and not weight sensitive
  • With respect to obesity, data is considered limited and poor to fair quality but suggests reduced effectiveness, especially with levonorgestrel

Learn More – Primary Sources:

Cochrane 2017: Interventions for emergency contraception

Safety and effectiveness data for emergency contraceptive pills among women with obesity: a systematic review

IUD, Hysterectomy or Ablation for Menorrhagia?

BACKGROUND AND PURPOSE:

  • Heavy menstrual bleeding accounts for 1/3 of gyn visits in the US
  • Multiple treatment options exist when conservative medical therapy (e.g. oral contraceptives) are not sufficient for good control
  • Spencer et al. (AJOG, 2017) evaluated the relative cost effectiveness of 4 possible treatments

METHODS:

  • Researchers constructed a hypothetical cohort of 100,000 premenopausal women
  • Researchers developed a decision tree which weighed a private payer cost with quality-adjusted life years (QALYs) over 5-years for women with heavy menstrual bleeding
  • 4 treatment options
    • Hysterectomy
    • Resectoscopic endometrial ablation (REA),
    • Non-resectoscopic endometrial ablation (NREA)
    • Levonorgestrel-releasing intrauterine system (LNG-IUS)
  • Each treatment option’s probabilities of minor complications, major complications, and treatment failure was derived from literature review
  • Treatments were compared in terms of total average cost, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio

RESULTS:

  • Compared to hysterectomy:
    • LNG-IUS had superior quality of life outcomes with lower costs
    • After analysis, LNG-IUS was more cost-effective in 90% of scenarios
    • Both REA and NREA had reduced costs, but lower average quality of life
    • Hysterectomy is associated with superior quality of life and fewer complications but more expensive than other treatments

CONCLUSION:

  • Strong evidence that LNG-IUS is a cost-saving alternative to hysterectomy for heavy bleeding with comparable quality of life outcomes but reduced costs
  • If LNG-IUS is not an option (patient choice or clinical reasons), decision is not as clear
    • Hysterectomy results in better quality of life and fewer complications than either type of ablation but at higher cost
    • Cost, potential complications and patient choice may drive decision

Learn More – Primary Sources:

Cost effectiveness of treatments for heavy menstrual bleeding

Do Hormonal Contraceptives Protect Against BV and Potential HIV Infection?

BACKGROUND AND PURPOSE:

  • Studies have shown that the composition of the vaginal microbiome may also impact predisposition to STDs and BV
    • There is an association between BV and HIV susceptibility
  • Research also indicates that hormonal contraception may impact STDs and BV
    • Use of estrogen-containing contraceptives appears to decreases BV
    • Effect of progesterone inconclusive
  • This study by Brooks et al. (Contraception, 2017) aimed to explore the effects of hormonal contraceptives on the vaginal microbiome
    • Researchers also sought ascertained amount of H2O2-producing Lactobacillus abundance as a decrease in Lactobacillus and replacement by bacteria can result in BV

METHODS:

  • Retrospective Study
  • 16s rRNA genes from vaginal bacteria were sequenced and identified
    • Gene survey data was taken from the Human Vaginal Microbiome Project
  • 682 women who used a single form of birth control were included
    • Types of birth control were: condoms, combined oral contraceptives (COCs), depot medroxyprogesterone acetate (DMPA), or IUD, specifically the levonorgestrel-releasing intrauterine system (LNG-IUS)

RESULTS:

Compared to women using condoms,

  • COC (adjusted odds ratio 0.29, 95% CI 0.13-0.64) and DMPA (adjusted odds ratio 0.34, 95% CI 0.13-0.89) are both less likely to have BV-associated bacteria
    • Women who used COCs (adjusted odds ratio 1.94, 95% CI 1.25-3.02) had increased Lactobacillus species
    • Neither LNG-IUS nor DMPA was associated with Lactobacillus abundance

CONCLUSION:

  • Use of COCs significantly increased the odds of vaginal colonization by healthy lactobacilli
  • This study provides supporting data that COCs increase healthy, protective vaginal flora

Learn More – Primary Sources:

Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome

IUDs and Implants: How to Manage Potential LARC Complications

Use of long-acting reversible contraceptive (LARC) methods, both intrauterine devices and subdermal contraceptive implants, has increased dramatically in the past ten years.  Although the risk of complications is low, as use increases the absolute number of complications will increase.

CLINICAL ACTIONS:

Intrauterine device:

  • Pain
    • Lidocaine paracervical block reduces pain scores on insertion
    • Misoprostol does not improve pain scores and may be associated with nausea and vomiting
  • Strings not visualized
    • Rule out pregnancy and expulsion
    • Recommend backup contraception until IUD position can be verified
    • Recommend emergency oral contraceptives (if appropriate)
    • Ultrasound and X-ray of abdomen and pelvis can be used for localization
  • Possible expulsion
    • IUDs seen in the cervix are partially expelled and should be removed
      • Replacement or use of another method are both acceptable options
    • Low-lying IUDs (lower uterine segment) can be expectantly managed
  • Risk factors for expulsion include
    • Young age
    • Heavy menstrual bleeding and dysmenorrhea
    • Placement postpartum or post second trimester abortion
    • Presence of anatomic distortion of the uterine cavity
  • Uterine perforation
    • Is rare and generally asymptomatic
    • Usually occurs at the time of insertion
      • Do not use misoprostol routinely prior to insertion in nulliparous women but may be considered with difficult insertions
    • Rule out pregnancy and remove surgically unless the surgical risks of removal outweigh the benefits
  • PID
    • Can be treated with the IUD left in situ
    • Consider removal if no clinical improvement after 48-72 hours of antibiotics
  • Pregnancy with an IUD in place
    • Remove the IUD if the strings are visible or IUD within the cervix
    • IUD can be removed at time of procedure if patient elects termination
    • Evaluate for ectopic pregnancy

Implant:

  • Infection prevention
    • Use antiseptic technique and cover the insertion/removal site
    • Skin flora are the most common cause of infection
    • Remove implant if infection does not resolve
  • Bruising
    • Is common
    • Ice and anti-inflammatory medication can help
  • Nonpalpable implant
    • Locate with high frequency (>/= 10 MHz) ultrasound probe, two dimensional X-ray, or CT scan/fluoroscopy
    • Obtain a serum etonogestrel level if all studies are negative/equivocal
    • Refer to a surgeon with knowledge of the anatomy of the arm if implant is within muscle or neurovascular bundle
  • Pregnancy
    • Is rare
    • Remove the implant if the pregnancy is to be continued
    • Rule out ectopic pregnancy

SYNOPSIS:

LARCs are highly effective contraceptives with a low risk of complications.  Those mentioned above should be discussed with patients as part of informed consent.

KEY POINTS:

  • Recognition and prompt diagnosis/treatment of the untoward outcomes described above are important aspects of care
  • Overall, complication rates are low and LARCs remain a very effective mode of birth control

ICD-10 codes:

  • Z30.49 check/reinsertion/removal of implant
  • Z30.430 insertion of IUD
  • Z30.432 removal of IUD
  • Z30.433 removal and reinsertion of IUD

Learn More – Primary Sources:

ACOG Committee Opinion 672: Clinical challenges of long-acting reversible contraceptive methods

Prolactinoma: Early Detection, Evaluation and Management

CLINICAL ACTIONS:

Prolactinomas are generally benign prolactin-secreting tumors and account for 40-66% of all pituitary adenomas.  The vast majority are microadenomas (diameter < 1cm) and suppress the hypothalamic-pituitary gonadal hormonal axis, while 10% are macroadenomas (≥ 1cm) and may cause additional mass effects due to size.

History: Consider the following ‘red flags’

  • Oligo or amenorrhea and galactorrhea (common presentation)
  • Loss of libido
  • Infertility
  • Osteoporosis
  • Mass effects:
    • Headache
    • Visual field abnormalities

Evaluation:

  • MRI to assess size and type of tumor
    • Prolactin levels above 200 µg/L is usually a prolactinoma
    • Prolactin levels above 500 µg/L likely indicates a macroprolactinoma
    • Non-prolactin secreting pituitary adenomas can cause pituitary stalk or hypothalamus compression and consequent prolactinemia
    • No tumor seen – ‘idiopathic’
  • TSH, free thyroxine (FT4), and creatinine levels to exclude secondary causes

Treatment:

  • Minimal symptoms (mild galactorrhea and normal menses): observation and monitor q6-12 months may be acceptable
  • Oligo or amenorrhea (pregnancy not desired): oral contraceptives or other estrogen/progesterone combinations
  • Most patients placed on dopamine agonists
    • Cabergoline > bromocriptine in reducing prolactin levels
  • Transsphenoidal surgery
    • Can result in normal prolactin levels in majority of microadenomas and up to 40% in macroadenomas
    • Recurrence is possible (20% over 10 years)
  • Radiotherapy
    • Rarely used for those cases that do not respond to the above
  • Chemotherapy
    • Temozolamide rarely used with limited success
  • In pregnancy: (estrogen stimulus)
    • Dopamine agonists are FDA ‘class B’ with no evidence of harm in humans, however, usually stopped and restarted if ‘mass effect’ symptoms develop

SYNOPSIS:

The prevalence of prolactinomas is reported to be between 35 to 50 per 100,000.  They are most commonly seen in women (10:1 ratio female/male) and the usual age range is between 20 to 50 years of age. Dopamine originating in hypothalamic neurons is a principal inhibitory regulator of prolactin release by pituitary lactotrophs and this pathway is the basis of medical treatments.  Fortunately, only a minority of microadenomas will continue to grow (< 10%) but early detection, monitoring and a management plan, which may be multidisciplinary, is required for good outcomes. Consider accessing expertise in endocrinology and radiology to ensure correct differential between prolactinoma and non-secreting pituitary adenoma as treatment for the latter is usually surgical, not medical.

KEY POINTS:

Severe adverse effects of dopamine inhibitors are unusual but cabergoline may include compulsive behavior (e.g. excessive gambling) as well as cardiac valvular abnormalities at high doses

  • Other causes of hyperprolactinemia include
    • Pituitary disorders (e.g. Cushing disease)
    • Hypothalamic disorders (e.g. non-secreting pituitary adenoma)
    • Neurogenic (e.g. chest wall or spinal cord lesions)
    • Medical
      • Hypothyroidism
      • Chronic kidney disease
      • Cirrhosis
    • Medications
      • Antipsychotics (e.g. phenothiazines)
      • Antidepressants (e.g. tricyclics, MAOIs, SSRIs)
      • Antihypertensives (e.g. verapamil, labetolol)
      • Anticonvulsants (e.g. phenytoin)
      • Prokinetics (e.g. metoclopramide)
      • Hormones (e.g. estrogen)
      • H2 blockers (e.g. cimetidine, ranitidine)
      • Controlled substances (e.g. opiates, cocaine, marijuana)
      • Other (e.g. alcohol)
    • Diagnosis code:

Learn More – Primary Sources:

Orphanet J Rare Disease: The risks of overlooking the diagnosis of secreting pituitary adenomas

Diagnosis and Treatment of Pituitary Adenomas: A Review

Locate a Reproductive Endocrinologist:

REI Locator – ASRM

Expert Opinion: Over-the-Counter Contraceptives for Adolescents

PURPOSE

This article by Upadhya et al. (JAH, 2017) aimed to review the regulatory and scientific issues with changing oral contraceptives (OCs) to over-the-counter status for adolescents under 18 years of age.

METHODS

Expert Opinion

RESULTS

This review delves into information about: 1) how the process of switching a drug to over-the-counter status works, 2) risk of pregnancy and the safety of OC use in adolescents, 3) adolescents’ ability to properly use OCs, 4) access to over-the-counter OCs, 5) effects on sexual risk behaviors, 6) potential in reduction of occasions for doctors to inform adolescents about reproductive health care. There is strong rationale for allowing adolescents access to over-the-counter OCs if there occurs any regulatory change. OCs are effective and safe for adolescents, and easy access to OCs, condoms, and emergency contraception increases their use while not increasing sexual risk behaviors.

Learn More – Primary Sources

Over-the-Counter Access to Oral Contraceptives for Adolescents

Is there a Link Between Oral Contraception Use and Cancer Risk?

PURPOSE:

This study by Iversen et al. (AJOG, 2017) sought to explore the relationship between oral contraceptive use and cancer risk.

METHODS:

Prospective Cohort Study

RESULTS:

46,022 women were recruited for this study between 1968-1969 and were followed up for 44 years. Long term users of combined oral contraceptives were compared to women who had never used. 4,661 of the 884,895 (0.005%) ever users had at least one cancer, compared to 2,341 of the 388,505 (.006%) never users. Ever use of oral contraceptives was associated with lower incidences of colorectal, endometrial, ovarian, and lymphatic and hematopoietic cancers. Increased risk of breast and cervical cancer was seen in current and recent users, but appeared to be lost within five years of stopping oral contraception, with no further increased risk in either of these cancers over time. This long-term study found that the majority of women taking oral contraceptives do not have an increased risk for cancer, and many benefit from reductions in risk of certain cancers.

Learn More – Primary Sources:

Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study

Does Use of Oral Contraceptives Impact Risk of MS Relapse?

PURPOSE:

This study by Bove et al. (Multiple Sclerosis, 2017) evaluated the relationship between oral contraceptives (OCs) and risk of relapse for women with multiple sclerosis (MS).

METHODS:

Longitudinal observational cohort study

RESULTS:

162 women with MS or clinically isolated syndrome (CIS) taking OCs who had begun injectable disease-modifying therapy within two years of diagnoses were studied. The study examined women who currently take OCs, had taken OCs in the past, and those who had never taken OCs. Women who had previously taken OCs had lower rates of relapse than those who had never take OCs. Annualized relapse rate was not significantly different across the three groups of women. Important conclusion based on the data – OC use does not increase risk of MS relapse.

Learn More – Primary Sources:

Oral contraceptives and MS disease activity in a contemporary real-world cohort

Optimizing Contraception for the HIV-positive Woman

The ideal contraceptive for an HIV-positive woman prevents pregnancy as well as transmission of HIV and STDs.  Dual contraception using condoms plus an additional contraceptive is the best strategy. Preexposure (PrEP) and postexposure (PEP) prophylaxis should be available to partners regardless of contraceptive method used.

There does not appear to be an association between the use of non-injectable hormonal contraception and risk of HIV acquisition. Studies regarding the risk of HIV acquisition with the use of progestin only DMPA injectable are conflicting, and the CDC continues to recommend it.

SUMMARY:

  • Combined hormonal contraception (pill, patch and ring) and progestin-only pills
    • Considered MEC cat. 1 for patient who are not on antiretrovirals or are not clinically well
    • For patients who are taking antiretrovirals, can decrease hormone levels but are still considered safe (either cat. 1 or 2 depending on which antiretroviral is being used)
    • Protease inhibitors, pharmacologic boosters, and efavirenz can cause decreased effectiveness of hormonal contraception
    • Fostemsavir: can cause increased levels of ethinyl estradiol and raise risk of thromboembolic events. Dosing of ethinyl estradiol should not be higher than 30 mcg daily.
  • Contraceptive implants are highly effective and benefits outweigh risks in HIV positive women (MEC cat. 1)
  • Injectable depot medroxyprogesterone acetate (DMPA) is safe and effective (MEC cat. 1) and does not appear to have interactions with antiretrovirals
    • Studies regarding increased risk of HIV transmission and acquisition are conflicting.
  • Intrauterine devices, both copper containing and levonorgestrel-releasing
    • MEC cat. 1 for women with HIV who are clinically well and on antiretrovirals, with no known drug interactions with antiretrovirals
    • For women with HIV who are not clinically well or not on antiretrovirals, initiation of IUD is considered MEC cat. 2, but continuation for an already placed IUD is cat.1
    • Limited data suggest a low risk of pelvic inflammatory disease and no changes in genital shedding of HIV RNA
  • Condoms reduce transmission of HIV between discordant partners but are not represent optimal contraception, with an annual pregnancy rate of over 15% per year. Should be used concurrently with another contraceptive method
  • Spermicides: not recommended due to potential of causing genital lesions
    • Nonoxynol-9, the active ingredient in most formulations, can cause genital lesions and may increase the likelihood of HIV transmission to a partner

KEY POINTS:

  • HIV infection does not pose a barrier to sterilization, which remains an appropriate contraceptive option
  • Emergency contraception including hormone based (progestin-only pills, ulipristal acetate, combined oral contraceptives) and the copper IUD should be offered to HIV positive women whenever appropriate
  • Spermicides and are not recommended

Learn More – Primary Sources:

CDC United States medical eligibility criteria for contraceptive use, 2016

Contraception: Contraceptive failure in the United States

Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV

HIV in Women: National HIV Curriculum

Practical info for your gynecology practice

Hormonal Contraception Benefits – Beyond Pregnancy Prevention

Hormonal contraception, as a class, can be used to correct menstrual abnormalities, increase predictability and reduce blood loss, among other benefits.

CLINICAL ACTIONS:

Consider hormonal contraception to address the following:

  • Dysmenorrhea
  • Excessive menstrual bleeding
  • PMDD / PMS
    • Combined oral contraceptives (OCs) only – 30 mcg ethinyl estradiol, drospirenone
  • Menstrual migraines without focal neurologic signs, nonsmokers, under 35 years of age
    • Extended cycle or continuous hormone contraception
  • Hirsutism/ acne
    • Combined OCs only
    • Ring, patch and progestin-only as methods are less effective

SYNOPSIS:

Control of menstrual bleeding is a significant benefit of hormonal contraception methods. In addition, OC users have a 50% reduction in risk of endometrial cancer, a benefit that persists for up to 20 years after use. The levonorgestrel intrauterine system effectively treats endometrial hyperplasia without atypia; however, data are limited in its role in hyperplasia with atypia. Reduction in risk of ovarian cancer parallels the duration of combined OC use, with a decrease of about 20% for every 5 years of use. Recent, but not past, use of OCs appears to lower risk of colorectal cancer.

KEY POINTS:

  • Hormonal contraception probably has no role in the following:
    • Prevention/treatment of follicular or corpus luteum cysts
    • Prevention/treatment of osteopenia or osteoporosis
    • Prevention of the development of leiomyomas
  • Bone loss during contraceptive use is likely analogous to that which occurs with breastfeeding and is rapidly reversed
    • Past users of DPMA and progestin implants have similar bone densities to non-users
  • Diagnosis codes:
    • Dysmenorrhea N94.6
    • Menorrhagia N92.4
    • Premenstrual dysphoric disorder F32.81
    • Menstrual migraine G43.829

Learn More  – Primary Sources:

ACOG Practice Bulletin No. 110 : Noncontraceptive Uses of Hormonal Contraceptives

PCOS: Targeting Treatments to Improve Reproductive Outcomes and Reduce CVD

Polycystic ovary syndrome (PCOS) is poorly understood and is characterized by varying degrees of hyperandrogenism, ovarian dysfunction and polycystic ovaries.  Due to insulin resistance, women with PCOS are at increased risk for metabolic syndrome and consequent diabetes and cardiovascular events.  Unopposed estrogen may result in endometrial cancer. Once identified, women need to be counseled and treated appropriately to reduce their risk of these health problems.

CLINICAL ACTIONS:

Treatment for Menstrual Disorders

Women with PCOS who are not attempting to conceive:

  • Combined oral contraceptives suppress luteinizing hormone secretion, ovarian androgen secretion and increase circulating sex hormone binding globulin (SHBG)
    • Recommended for primary treatment of menstrual disorders
    • May also be used to treat hirsutism
  • Progestin-only contraceptives or progestin containing IUDs protect the endometrium but lead to abnormal bleeding patterns in over 50% of patients
  • Insulin sensitizing agents, including biguanides (metformin) and thiazolidinediones (pioglitazone, rosiglitazone)
    • The use of insulin sensitizers are associated with decrease in androgen levels, improved ovulation, improved glucose tolerance
    • Important to discuss contraception
    • The insulin sensitizing agents are not currently approved by the FDA for the treatment of PCOS
      • Metformin, according to ACOG has the “safest risk-benefit ratio”
      • The International Guideline recommends metformin for those women with metabolic features of glucose intolerance/ insulin resistance

Treatment for Hirsutism

Women with PCOS can be treated with the following:

  • Spironolactone, a diuretic, aldosterone antagonist, androgen receptor antagonist: 25-100 mg twice daily
    • May take up to 6 months to be effective
  • Flutamide, an androgen-receptor antagonist 125-250 mg/day: Teratogenic
  • Finasteride, a 5-alpha-reductase inhibitor, 1-5 mg/day: Teratogenic
  • Topical eflornithine, an inhibitor of ornithine decarboxylase, twice daily application for facial hair
  • Mechanical hair removal (electrolysis, laser vaporization, shaving, plucking, waxing, depilatory creams)

Treatment to Reduce Cardiovascular and Diabetes Risks

Women with PCOS who are not attempting to conceive:

  • Lifestyle modification (e.g. regular exercise and weight loss)
    • Weight loss is the primary therapy in PCOS: As little as 5% reduction in weight can restore regular menses and improve response to fertility medications
    • No advantage in any particular diet – caloric restriction is the key factor
  • Insulin sensitizing agents such as metformin can delay development of diabetes in those at risk
    • Data currently insufficient to recommend insulin-sensitizing agents prophylactically for women at higher risk of diabetes due to PCOS
  • Statins lower testosterone, total and LDL cholesterol levels but do not improve menses, hirsutism or acne
  • No evidence that combined hormonal contraceptives or progestins will increase the risk of diabetes or CVD in women with PCOS

Treatment for Women with PCOS Planning to Conceive

First-Line Interventions

  • Letrozole
    • Letrozole (aromatase inhibitor) is considered a first-line treatment due to data demonstrating increased ovulation rates, clinical pregnancy rates and live-birth rate vs clomiphene citrate
    • Counsel patients that letrozole is not approved by the FDA for ovulation induction
    • Letrozole starting dose is 2.5 mg/day for 5 days starting day 3, 4 or 5 of cycle and increase to 5 mg/day for 5 days with a maximum dosage of 7.5 mg/day if ovulation does not occur at lower, initial dose
  • Clomiphene Citrate
    • ‘Traditional’ first-line treatment with improved performance compared to metformin alone or placebo
    • Over 50% of those who conceive do so on 50 mg/day dose and 20% on 100 mg/day dose
    • Most pregnancies occur within 6 months
  • Both clomiphene citrate and letrozole are associated with increase in multiple births, preterm birth, and hypertensive disorders

Second-Line Interventions

  • If clomiphene citrate or letrozole fails
    • Gonadotropins
    • Laparoscopy with ovarian drilling

Third-Line Intervention 

  • The International Guideline considers IVF to be a third line intervention for PCOS

Diabetes Assessment

Screening for Diabetes

  • Assess glycemic status at baseline in all women at time of PCOS diagnosis and repeat every 1 to 3 years depending on other risk factors
  • To assess glycemic status, use one of the following tests
    •  Oral glucose tolerance test (OGTT)
    • Fasting plasma glucose
    • HbA1c
  • OGTT is recommended in women with PCOS and risk factors
    • BMI > 25 kg/m2
    • Asians > 23 kg/m2
    • History of impaired fasting glucose
    • Impaired glucose tolerance or gestational diabetes
    • Family history of diabetes mellitus type 2
    • Hypertension
    • High-risk ethnicity

Women considering fertility treatment or preconception planning 

  • Prior to fertility treatment and/or preconception planning
    • Offer all women a 75-g OGTT
  • In pregnancy
    • If not performed preconception, offer OGTT<20 weeks
    • Offer all pregnant women with PCOS an OGTT at 24-28 weeks gestation

SYNOPSIS:

Once diagnosed, treatment of PCOS should be tailored to patient’s risk factors and desires.  Lifestyle modifications including weight reduction and regular exercise have been shown to decrease the metabolic and hormonal effects of PCOS. Treatment regimens are based on protecting the endometrium from the effects of unopposed estrogen, reestablishing a regular menstrual cycle, preventing the metabolic syndrome and cardiovascular sequelae of PCOS, and providing support for ovulatory dysfunction in those anticipating pregnancy.

KEY POINTS:

  • ACOG Practice Bulletin updated based on recent data that letrozole outperforms clomiphene citrate for ovulation induction
    • Higher live-birth rate: 27.5% vs 10.1% (P=0.007) with odds ratio of 1.64 (95% CI, 1.32-2.04)
    • Higher ovulation rate: 61.7% vs 48.3% (P<0.001)
    • Higher clinical pregnancy rate: Odds ratio of 1.40 (95% CI, 1.18-1.65)
  • Before starting medical/surgical ovulation induction therapies, counsel about lifestyle modification including
    • Stop smoking
    • Reduce weight and increase exercise especially in setting of overweight/obesity
    • Reduce alcohol consumption
  • Both letrozole and clomiphene citrate are contraindicated in pregnancy

Learn More – Primary Sources:

ACOG Practice Bulletin No. 194: Polycystic ovary syndrome

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

EJE: MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME–PART 1

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME – PART 2