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Urine and serum hCG were negative. A complete blood count (CBC) revealed mild iron-de ciency anemia. Thyroid-stimulating hormone (TSH) and prolactin were normal. A hormonal pro le revealed the following on cycle day 47: estradiol 38 pg/mL, luteinizing hormone (LH) 4 IU/L, follicle-stimulating hormone (FSH) 5.1 IU/L, anti-Mullerian hormone 1.10 ng/mL.
A diagnosis of anovulatory cycles following long-term COC use was made. The patient was subsequently monitored over the following 3–4 months. Her cycle lengths became somewhat shorter; however, cycles still occurred every 40–50 days. As the couple was interested in conceiving, the patient began clomiphene citrate for ovulation induction. She ultimately conceived after three cycles of clomiphene citrate and timed intercourse and is now in her second trimester.
Discussion
Abnormal uterine bleeding (AUB) is de ned as menstrual fow outside of the normal volume, duration, regularity, or frequency. The American College of Obstetricians and Gynecologists (ACOG) supports the adoption of the PALM- COEIN nomenclature system developed by the International Federation of Gynecology and Obstetrics (FIGO) in 2011, which divides the etiologies of AUB into structural and non-structural causes (Fig. 8.1).
The pathophysiology of AUB can be roughly divided into two categories: ovulatory AUB and AUB due to ovulatory dysfunction. With ovulatory AUB, the hypo- thalamic–pituitary–ovarian axis is intact and steroid hormone pro les are generally normal. Common mechanisms include abnormal prostaglandin synthesis and receptor upregulation [1], increased brinolytic activity [2], and increased tissue plasminogen activator activity [3]. In contrast, AUB due to ovulatory dysfunction is typically due to an endocrinopathy, such as polycystic ovary syndrome (PCOS), thyroid disease, hyperprolactinemia, and other mechanisms related to unopposed estrogen.
When the cause of AUB is being determined, we favor a differential diagnosis approach guided by the age of the patient. In reproductive-aged women as in our case example, the most common causes are pregnancy, anovulation, an endocrinopathy, structural causes (polyps, broids, adenomyosis), medications, infections, and malignancy. In premenarchal girls, special considerations should include a foreign body, trauma or abuse, sarcoma botryoides, and precocious puberty as differentials. In adolescence, anovulation due to hypothalamic immaturity is most common, but other special considerations may include hypothalamic stress (exercise-induced or an eating disorder) or coagulation disorders. In post- menopausal women, atrophy, malignancy, and medication effects should be suspected.
The evaluation of AUB starts with a detailed history, including the age of menarche (and menopause if applicable), the menstrual bleeding pattern (timing, frequency, last menstrual period, duration, quantity), associated symptoms (pain,
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8 Abnormal Uterine Bleeding |
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Abnormal Uterine Bleeding (AUB)
-Heavy menstrual bleeding (AUB/HMB) - lntermenstrual bleeding (AUB/IMB)
PALM: Strutural Causes
Polyp (AUB-P) Adenomyosis (AUB-A) Leiomyoma (AUB-L)
Submucosal myoma (AUB-LSM) Other myoma (AUB-Lo)
Malignancy & hyperplasia (AUB-M)
COEIN: Nonstrutural Causes
Coagulopathy (AUB-C) Ovulatory dysfunction (AUB-O) Endometrial (AUB-E) Iatrogenic (AUB-I)
Not yet classified (AUB-N)
Fig. 8.1 AUB nomenclature. Source: Diagnosis of Abnormal Uterine Bleeding in Reproductive- Aged Women. Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. July 2012 (Reaf rmed 2016)
vaginal discharge, fever), screening for signs and symptoms of possible hemostatic disorder, as well as pertinent medical, surgical, medication, and family histories [4]. Physical exam should pay special attention to the presence or absence of ecchymosis, thyromegaly, clinical signs of hyperandrogenism (hirsutism, acne, male pattern balding), or acanthosis nigricans. Laboratory testing should include a pregnancy test (blood and/or urine), as well as a CBC, TSH, prolactin, and targeted screening for bleeding disorders. When appropriate, a Pap smear and cultures for Chlamydia trachomatis/Gonorrhea should be obtained. In post-pubertal women, estradiol, luteinizing hormone (LH), and progesterone levels can help determine ovulatory status. Transvaginal ultrasonography is the primary imaging modality utilized in the evaluation of AUB in reproductive age and post-menopausal women. Saline infusion sonohysterography (SIS), magnetic resonance imaging (MRI), and hysteroscopy may also be bene cial in cases of structural lesions. Endometrial sampling should be performed in women with unopposed estrogen exposure, as well as those with risk factors for endometrial hyperplasia—obesity, chronic anovulation (PCOS), history of breast cancer, SERM (tamoxifen) use, family history of endometrial, ovarian, breast, or colon cancer and/or thick endometrial lining on ultrasound.
Treatment options depend upon the etiology of the AUB and the patient’s overall goals, namely whether the patient is attempting to conceive in the future (either in the near or long term). When AUB is thought to be due to an endocrinopathy or
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bleeding disorder, appropriate medical management is indicated. In cases of anovulatory bleeding or unopposed estrogen, medical therapy is often very effective. Medical treatment options may include conjugated equine estrogen (acute), combined oral contraceptives, a cyclic progestin (e.g., medroxyprogesterone acetate), tranexamic acid (acute or chronic), levonorgestrel intrauterine device, or gonadotropin releasing hormone agonist (leuprolide). In cases of failed medical therapy or known surgical indication (structural causes), hysteroscopy/D&C, endometrial ablation, or hysterectomy (de nitive treatment) may be indicated. In cases of atypical hyperplasia or malignancy, we would refer to a gynecologic oncologist for further evaluation and de nitive treatment.
In conclusion, AUB is an extremely common reason for women to present for gynecologic evaluation. We recommend a diagnostic and treatment approach guided by the age of the patient and her overall goals.
References
1.\ Smith SK, Abel MH, Kelly RW, Baird DT. Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding. Br J Obstet Gynaecol. 1981;88(4):434–42.
2.\ Dockeray CJ, Sheppard BL, Daly L, Bonnar J. The brinolytic enzyme system in normal menstruation and excessive uterine bleeding and the effect of tranexamic acid. Eur J Obstet Gynecol Reprod Biol. 1987;24(4):309–18.
3.\ Gleeson N, Devitt M, Sheppard BL, Bonnar J. Endometrial brinolytic enzymes in women with normal menstruation and dysfunctional uterine bleeding. Br J Obstet Gynaecol. 1993;100(8):768–71.
4.\ Diagnosis of abnormal uterine bleeding in reproductive-aged women. Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. July 2012 (Reaf rmed 2016).
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Chapter 9
Hirsutism
Nina Vyas and Joshua Stewart
Case
A 51-year-old multiparous woman presents with progressive hair growth on her face and lower abdomen. She reports menarche at age 11 and she was diagnosed with polycystic ovarian syndrome (PCOS) in her teens. Her diagnosis at that time was presumably based on elevated serum testosterone concentrations and irregular menses. For most of her reproductive years, she was placed on oral contraceptive pills and used depilatories to remove unwanted hair growth. In her early 30s, she successfully conceived twice with the use of clomiphene citrate for ovulation induction and has had two healthy children. Recently, she visited her gynecologist as she believed she was in menopause after being amenorrheic for over 12 months with climacteric symptoms of vaginal dryness and hot ashes. She also told her gynecologist that during these past 12 months, she has noticed a gradual increase of thick and dark hairs on her chin, lower abdomen, and upper inner thighs as well as a receding hair line. Her husband has noticed a deepening in her voice. Her gynecologist referred her to a reproductive endocrinologist for further evaluation.
In addition to the diagnosis of PCOS, her medical history is signifcant for insulin-dependent type 2 diabetes mellitus, anxiety, and depression. She has had two prior cesarean deliveries, and no other surgical history. Her medications include nightly and meal-time insulin as well as oral metformin. She has no allergies to any medications. Her family history is signifcant for a history of PCOS in her mother and hypertension in her father. There is no family history of cancer. She has a remote history of tobacco use, denies illicit drug use, and consumed alcohol occasionally.
On physical exam, she had normal vital signs and a BMI of 31.4 kg/m2. On inspection, she had dark hairs on her chin and lower abdomen, with a
N. Vyas · J. Stewart (*)
Reproductive Medicine and Ob/Gyn, The Ronald Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA e-mail: jds9013@med.cornell.edu
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P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_9