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.
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
Prolactinoma: Early Detection, Evaluation and Management
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
Visual field abnormalities
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
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
Can result in normal prolactin levels in majority of microadenomas and up to 40% in macroadenomas
Recurrence is possible (20% over 10 years)
Rarely used for those cases that do not respond to the above
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
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.
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
Expert Opinion: Over-the-Counter Contraceptives for Adolescents
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.
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.
Is there a Link Between Oral Contraception Use and Cancer Risk?
This study by Iversen et al. (AJOG, 2017) sought to explore the relationship between oral contraceptive use and cancer risk.
Prospective Cohort Study
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.
Does Use of Oral Contraceptives Impact Risk of MS Relapse?
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).
Longitudinal observational cohort study
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.
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.
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
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
Hormonal contraception, as a class, can be used to correct menstrual abnormalities, increase predictability and reduce blood loss, among other benefits.
Consider hormonal contraception to address the following:
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
Combined OCs only
Ring, patch and progestin-only as methods are less effective
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.
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
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.
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:
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
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
‘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
If clomiphene citrate or letrozole fails
Laparoscopy with ovarian drilling
The International Guideline considers IVF to be a third line intervention for PCOS
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
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
Women considering fertility treatment or preconception planning
Prior to fertility treatment and/or preconception planning
Offer all women a 75-g OGTT
If not performed preconception, offer OGTT<20 weeks
Offer all pregnant women with PCOS an OGTT at 24-28 weeks gestation
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.
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
Reduce weight and increase exercise especially in setting of overweight/obesity
Reduce alcohol consumption
Both letrozole and clomiphene citrate are contraindicated in pregnancy
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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