Clinical:Case Study: Endometriosis

Original materials created in December 2000 by Rebecca Rosen, M.D.

History

T.S. is a 24 y.o. G1P1 8 months postpartum. She complains of excruciating back pain in the sacral area as well as left lower quadrant pain. The pain worsens about one-and-a-half weeks prior to her periods and continues during her menses. She gets only mild relief with NSAIDs and sometimes resorts to Tylenol #3. Since the delivery, she has been taking oral contraceptive pills; the pills regulate her cycles but do not seem to alleviate the pain.

T.S. recounts that during her pregnancy she was pain-free for the first time in five years. The perimenstrual pain began when she was around nineteen. On further questioning she notes occasional dyspareunia especially during or just before menses.

Past History

No surgeries. NSVD eight months ago, no complications. Was breastfeeding up to four months ago. Menarche age twelve with menses every twenty-eight days, duration four days. No tobacco or alcohol.

Pelvic Exam

Pelvic exam (done during early menses) reveals a retroverted uterus, tender to palpation, and tender nodular masses along thickened uterosacral ligaments. External genitalia, cervix and vaginal mucosa are unremarkable. PAP, GC and Chlamydia are negative

Endometriosis is suspected. As OCPs, a first-line empiric therapy, do not alleviate symptoms, TS agrees to try leuprolide acetate (Depo Lupron), a GnRH analogue. This will help control the symptoms while awaiting laparoscopy for diagnostic confirmation.

Discussion

Endometriosis is the presence of hormonally responsive endometrial tissue outside the uterus. It progresses under repetitive influence of menstrual cycle hormones, and, although generally benign, can spread extensively. An endometrioma is an area of endometriosis sufficiently large to be classified as a tumor i.e., a “chocolate cyst.” Prevalence is 5-10% and the mean age is 25 to 30 years old. It is found in 4.1% of asymptomatic women undergoing sterilization and has been noted in 20% of women undergoing laparoscopic workup for infertility.

An estrogen-dependent condition, endometriosis is increased by early menarche, regular cycles (especially without interruption by pregnancy), and longer and heavier flow. Conversely, endometriosis is less likely in estrogen deficient states such as menstrual disorders, decreased body fat, and tobacco use.

Theories of the pathogenesis include retrograde menstruation, coelomic metaplasia, and Müllerian cell remnants. There is a 7% risk of having endometriosis if it is present in a first degree relative.

There are no pathognomonic symptoms but common presentations are pelvic pain (constant or cyclical), infertility, or pelvic mass. GI or urinary obstruction is rare but does occur. Secondary dysmenorrhea with pain prior to menses, deep dyspareunia exaggerated during menses, and sacral backache with menses are the most common complaints at presentation.

Physical exam should be done during early menses when implants are likely to be largest and most tender. Note that most women have normal pelvic findings, however.

The differential diagnosis of endometriosis includes pelvic inflammatory disease, pelvic adhesions, ovarian torsion, neoplasms, sexual or physical abuse, and primary dysmenorrhea.

Diagnosis

Suspect endometriosis in women with complaints of pelvic pain or infertility. Inquire about past physical/emotional abuse as pelvic pain can be a manifestation of this. Inquiry also about the cycle of pain. Definitive diagnosis requires laparoscopy and and biopsy. The common sites are found in the dependent portions of the pelvis: ovary, posterior cul-de-sac, broad ligament, uterosacral ligament, rectosigmoid colon, bladder, distal ureter. Endometriosis does occur at extra-pelvic sites via hematogenous/lymphatic spread.

Treatment

The three basic approaches are expectant management, medical treatment, and surgical treatment. Patients with only minimal symptoms may be observed for 5 – 12 months. NSAIDs can help mild to moderate pain, and narcotic analgesia may sometimes be necessary.

Medical treatment is suppressive not curative. The goal is to simulate a hypoestrogenic state in order to bring about atrophy of implants. Oral contraceptive pills prevent ovulation which results in decidualization (thinning) of the endometrium (and of endometrial implants). OCPs also result in decreased menstrual volume and thus less retrograde menstruation. 75-89% of patients treated with OCPs report relief. Patients may use OCPs continuously (without placebo pills) up to a year or longer. Progestins function similarly to combination OCPs. The dosage: PO 10 – 30mg/day or IM: 100mg every 2 weeks for 4 doses(2 months) followed by 200mg IM q month for 4 months.

Danazol has been used since 1971. It inhibits FSH and LH, decreasing ovarian estrogen and progesterone production, and also increases androgen effects with direct inhibition of endometrial growth. Dosage is 400 mg/day divided bid to qid (max 800 mg/day) and can be started after or with menses (avoid fetal exposure). Barrier contraception should be used during the first few months. Treatment is usually 6 months. The overall response rate is 84- 92% and benefits may last up to six months after cessation. Disadvantages include side effects such as weight gain, headache, fluid retention, hot flushes and decreased HDL levels.

GnRH analogues bind to pituitary receptors, resulting in a hypogonadotropic, hypogonad state or “medical oophorectomy.” Without estrogen support endometriotic implants regress. Up to 90% of patients report relief. GnRH analogues include Leuprolide Acetate 3.75mg in monthly depot form, Goserelin 3.6 mg sq every 28 days, Nafarelin Acetate intranasally bid. Side effects are consistent with a hypoestrogenic state. Treatment is limited to 6 months due to significant trabecular bone loss. Surgery is superior in treating infertility and endometriomas compared with medical therapy alone. Diagnosis and initial treatment are simultaneous with surgical ablation of lesions on diagnostic laparoscopy. Implants recur in up to 28% of patients within 18 months and in 40% after 9 years. Overall, 61-100% of patients cite relief. Conservative surgery retains fertility and is preferred for infertile patients with advanced disease. TAH/ BSO along with excision/ablation of implants is 90% effective and is definitive treatment for women who do not desire further childbearing.

A combination of medical and surgical treatments is the general current standard. Danazol as well as the GnRH analogues can be used pre- and post-op to decrease implant size and prevent new ones.

It is critical to remember that as with any patients dealing with chronic pain, NSAIDs, SSRIs and therapy/ support groups need to be offered/ considered.

T.S. tried Depo Lupron for three months prior to her diagnostic laparoscopy. While she did report pain relief, she also complained of terrible headaches, flushing, nausea, and vomiting for the first week after each monthly injection. These side effects waned with time but she elected to forego additional medical therapy postoperatively as the laparoscopic adhesion lysis and lesion ablation alleviated her pain. At one year post-op she is still pain free and has elected to continue with OCP’s for birth control as well as possible prophylaxis.

References

1)Lu PY, Ory SJ. Endometriosis: Current Management. Mayo Clin Proc 1995; 70:453-463

2)Wellbery, C. Diagnosis and Treatment of Endometriosis. American Family Physician Oct. 15, 1999

3)Hull ME, et al. Comparison of different treatment modalities of endometriosis in infertile women. Fertil Steril 1987; 47:40-4