When hormonal contraception was introduced to the United States in 1960, it marked the first time couples could plan their fertility with a discreet, reversible noncoitus-related method that was highly reliable. Over the ensuing almost 50 years, hormonal contraception has continued to be refined. It has also become recognized for a number of health benefits.

Today, several forms of hormonal contraception have indications for noncontraceptive use (Table 1). And many formulations and delivery methods have evidence-based, albeit off-label, indications for health benefits beyond family planning. With careful selection of both method and patient, nurse practitioners can now offer women effective contraception plus improved skin, decreased menstrual-related symptoms, decreased menstrual bleeding and pain, migraine management and decreased risk for gynecologic cancers.

Acne Management

All forms of hormonal contraception contain progestin, a synthetic progesterone. The original progestin was norethindrone, derived from C-19 androgen. Subsequent progestin products have been less and less androgenic. As potency has increased, doses in combined estrogen-progestin oral contraceptives (COCs) have decreased. The newest progestin, drosperinone (in Yaz and Yasmin), is an analog to spironolactone and is antiandrogenic.

All progestins increase sex hormone-binding globulin. This reduces circulation of androgenic hormones and prohibits release of luteinizing hormone, reducing ovarian androgen production. These actions decrease the size and number of cystic acne lesions.^1,2

Three COC formulations have FDA indications for the treatment of acne: norgestimate-ethinyl estradiol triphasic (Ortho Tri-Cyclen), norethindrone acetate-ethinyl estradiol triphasic (Estrostep) and drosperinone-ethinyl estradiol (Yaz). When choosing a hormonal contraception for women who desire control of acne, selecting for decreased androgenicity of the progestin component in any COC provides evidence-based, effective intervention.

Premenstrual Symptoms

For many years, patients and providers believed that exposure to ovarian hormones was responsible for the emotional lability, breast tenderness, bloating, headaches and pelvic pain that make up the symptoms of premenstrual syndrome (PMS). Studies examined the effects of decreased hormone doses in the hope of reducing the symptoms believed to be associated with estrogen and progesterone.

The overall results showed that withdrawal from these hormones in oral contraceptive (OC) users correlates more closely with symptom onset.³Active pills for 24 days, followed by a shorter 4-day, pill-free interval (such as in Yaz) is the only regimen that showed significant reduction in menstrual-related symptoms when compared to traditional 21/7 dosing regimens. This was true even in a head-to-head comparison with the similar formulation of drosperinone-ethinyl estradiol in a 21/7 dosage regimen (Yasmin). Yaz has an FDA indication to treat emotional and physical symptoms of premenstrual dysphoric disorder that are severe enough to affect the lives of women who choose OCs for contraception.⁴Any regimen that reduces the pill-free interval can reduce premenstrual symptoms. Two products are available to deliver this approach: extended monophasic COCs in a regimen of an active levonorgestrel-ethinyl estradiol pill for 84 days, followed by a 7-day pill-free interval (Seasonale) and active levonorgestrel-ethinyl estradiol for 84 days followed by ethinyl estradiol for 7 days (Seasonique).

Other long-acting progestins in COCs have also been studied in 84/7 regimens. Six randomized, controlled trials that included these variables documented significant improvement in menstrual symptoms of bloating, fatigue, genital irritation and headaches with extended cycles.⁵

The newest hormonal contraceptive on the market is continuous combined levonorgestrel (Lybrel) in 365-day dosing (90 mcg/EE 20 mcg). Studies assessing the effects of this product on menstrual-related symptoms are not yet available.

Patients benefit from anticipatory guidance about the body's adjustment to longer cycles. Many patients need reassurance that monthly withdrawal bleeding, as seen in a 21/7 regimen, is neither necessary nor health promoting. Symptom relief improves after several months of avoiding pill-free intervals. In the extended regimen, intended bleeding patterns (no breakthrough bleeding and positive withdrawal bleeding during the pill-free interval) do not differ from traditional 21/7 regimens by the second or third cycle.

Alternately, the combined etonogestrel-ethinyl estradiol vaginal ring (Nuvaring) has been studied for efficacy in 49- and 91-day cycles.⁶Although extended ring use is off-label at this time, evidence of effectiveness in ameliorating menstruation-related symptoms with two to three sequential 21-day ring uses, followed by a ring-free week, is both safe and contraceptively effective.

Extended-use cycles with continuous transdermal norelgestromin-ethinyl estradiol patches (Ortho Evra) are not recommended due to the lack of extended-use safety data and the higher serum estrogen levels with this method.⁷

Menorrhagia

The normal menstrual cycle is multiphasic. The follicular growth phase is characterized by increasing and dominant estrogen levels. This stimulates growth of the endometrial lining. After ovulation, while the corpus luteum in the ovary continues to produce estrogen, the dominant hormone produced is progesterone. Progesterone acts on the endometrial lining to suppress further growth and cause maturation of the glandular cells.

Thus, progesterone has an atrophic effect on the lining of the uterus. The continuous combined dose of both estrogen and progestin in hormonal contraception, whether delivered orally, transdermally (Ortho Evra) or transvaginally (Nuvaring), causes less endometrial development. Thus, all combined contraceptives reduce menstrual bleeding.⁸

Endometrial suppression is most significant with progestin-only methods. Studies have demonstrated efficacy with reduced blood loss, but there is typically a trade-off: a decrease in cycle control and an increase in breakthrough bleeding or spotting.⁹Progestin-only pills (Micronor, NorQD) contain low levels of progestin. They are sensitive to delayed doses; efficacy is reduced if a dose is more than 3 hours late.

Injectable progestin (Depo-Provera IM or Depo-Provera SC) provides 3 months of effective contraception anddecreased menstrual bleeding. Most women achieve amenorrhea with prolonged use. This method should not be selected for a woman who desires careful timing of a future pregnancy because it causes a delayed return to fertility after discontinuation.¹⁰

Implantable progestin (Implanon) has the advantage of long-term efficacy, quick return to fertility after discontinuation and elimination of user error.

The progestin-containing intrauterine system (Mirena) works locally to cause atrophy of the endometrium, resulting in dramatic reductions in menstrual bleeding. Within 12 months of insertion, approximately 50% of women develop amenorrhea and an additional 30% have light menstrual flow of 1 to 2 days' duration.¹¹

Mirena does not have an indication for use in nulliparous women, but studies of parous and nulliparous women have demonstrated the same efficacy and same differences (slightly increased rate of pain on insertion and slightly increased rate of spontaneous expulsion) associated with the FDA-approved copper IUD (Paragard), which is indicated for use in nulliparous women.¹²

he World Health Organization does not distinguish between nulliparous and parous women in its eligibility criteria for an intrauterine device or system.¹⁰Use of Mirena in nulliparous women to provide contraception and treat excess menses is off label, but not without supporting clinical evidence.

All progestin-only methods are excellent choices for women who desire menstrual bleeding reduction and have other health risk factors, such as hypertension, migraines with aura or history of deep vein thrombosis. ¹⁰

Dysmenorrhea and Endometriosis

Dysmenorrhea, or painful menstruation, is most common in younger women and nulliparous women. About 45% to 72% of older adolescents report being affected.¹³When other causes of menstruation-related pain are eliminated, particularly in new or acute onset, dysmenorrhea can be significantly reduced with most methods of hormonal contraception. Ninety percent of women report a marked decrease in menstrual pain within 3 to 4 months of starting COCs.¹⁴The same pattern of extended cycles (84/7 regimen) discussed in the section on menstrual-related symptoms also reduces menstruation-related pain due to the reduction of pain with COCs and the decreased episodes of vaginal bleeding. Likewise, progestin-only methods are effective for the treatment of dysmenorrhea because they reduce vaginal bleeding or induce amenorrhea.

Endometriosis is the presence of implants outside the uterine cavity that respond to the cyclic pattern of hormones with monthly growth and sloughing of endometrial lining. The local sloughing incites an inflammatory response, which can lead to fibrosis, scarring, tubal occlusion and infertility.

The exact etiology is not clear, but implants are thought to arise from retrograde menstruation and possible hematogenous and lymphatic spread. Family history of endometriosis in a first-degree relative is associated with a risk of disease six to seven times higher than average.¹³Affected women present with severe dysmenorrhea, often with onset just prior to vaginal bleeding. The effect of combined estrogen-progestin and progestin-only methods of contraception discussed in the section on the treatment of dysmenorrhea are also applicable in endometriosis. Injectable depot medroxyprogesterone acetate (Depo-Provera) has an FDA indication for the treatment of endometriosis.

Mirena has been studied for potential usefulness in endometriosis. When placed after surgical ablation of implants, women reported 50% reduction in symptoms compared with expectant management. Symptoms remained improved at 12 months of use, but the system did not demonstrate improvement beyond that time frame. Another study comparing Mirena to GnRH therapy documented symptom improvement in both groups.¹⁵Mirena is an effective treatment for endometriosis.

Therapy for endometriosis has a second goal, the preservation of fertility. Theoretical hopes that the chronic suppression of endometrial implant growth through hormonal contraception would prevent scarring and subsequent infertility have not been confirmed in the few trials that have been completed.¹⁶Hormonal contraception for endometriosis management does not appear to promise improved fertility, but further investigation is needed in this area.

Menstrual Migraine

Approximately 1 in 6 women of reproductive age experiences menstrual migraines. Pure menstrual migraine (7% to 9% of migraine sufferers) occurs exclusively in the 2 days before and 3 days after the onset of menses. Menstrually related migraines occur during this same perimenstrual time frame and at other times of the month.⁸The onset of headache is correlated with decreasing serum estrogen levels.¹⁷

Many patients with migraine believe that the diagnosis of migraine headache, rather than tension-type headache (90% of all headaches), is merely a matter of pain severity. Women with mild to severe headaches may volunteer a history of migraines even though no medical assessment has been performed. It is important to achieve a careful diagnosis because true migraine has many implications in the choice of contraception method (Table 2).

All migraines are associated with increased risk for ischemic stroke; migraineurs with aura have up to three times the stroke risk as people who are unaffected.⁸The addition of hormonal contraception further increases this risk.¹⁸Concurrent health conditions, such as hypertension, tobacco use and age older than 40, increase stroke risk whether or not aura is present. Women who experience migraines with aura and women older than 35 who experience migraines of any type should not use combined hormonal contraception.¹⁰

For women younger than 35 who have migraines without aura and who do not have concurrent smoking or hypertension, extended combined contraception in an 84/7 regimen or continuous combined levonorgestrel 90 mcg/EE 20 mcg (Lybrel) 365-day dosing reduces or eliminates estrogen withdrawal. In limited studies, this effectively reduced both the frequency and severity of migraines.¹⁹As with other menstrually related symptoms, relief is achieved after multiple extended cycles or multiple months of continuous dosing.

Gynecologic Cancer

The presence of progestin in combined hormonal contraception and progestin-only formulations controls the growth of the endometrial lining, preventing hyperplasia and subsequent risk for endometrial cancer. Twelve months of COC use provides a 40% reduction in endometrial cancer risk. COC use for 10 years reduces risk by 80%.²⁰Depo-Provera has also demonstrated efficacious and prolonged protection from endometrial cancer. Protection is enhanced in women who have risk factors for endometrial cancer, such as polycystic ovary syndrome or obesity.

The suppression of ovulation with hormonal contraception prevents subsequent endothelial damage and repair, reducing the development of cancer.²¹The use of COC for as little as 6 months provides protection from epithelial ovarian cancer. Continued use provides increased protection; 5 years of use reduces the risk of epithelial ovarian cancer by 50%. The protection persists up to 25 years after discontinuation.²²Although it is biologically plausible that a similar protective effect is provided by non-oral COC delivery methods such as the vaginal ring and patch, no studies have confirmed this.

Studies also demonstrate a link between ovarian cancer reduction and hormonal contraception in carriers of the oncogenes BRCA.²³Of concern is the possibility of a concomitant increase in breast cancer risk with hormonal contraception use in this group. The evidence of risk is not clear, however. Most studies showed no increase in breast cancer risk with hormonal contraception use in BRCA1 or BRCA2 carriers. One study showed an increased risk only in BRCA2 carriers who used hormonal contraception for longer than 1 year.²⁴More research is needed before guidelines are developed.

The connection between hormonal contraception and risk reduction in both ovarian and endometrial cancer is an area of opportunity for patient education. Ovarian cancer is the most deadly gynecologic cancer. Early-stage diagnosis is hampered by the lack of specific symptoms. Yet women remain largely unaware of well-documented preventive measures. In one large survey, only 12% of women knew that hormonal contraception provided ovarian cancer protection.²⁵

Putting It Into Practice

Nurse practitioners can enhance patients' health by thinking beyond contraception to the control of acne, the management of menstruation-related symptoms, the control of excess bleeding or pain with menstruation, the management of cyclic headaches, and the prevention of gynecologic cancers. Almost 50 years of product refinement, intense research and clinical experience ensure that hormonal contraception can provide women with much more than fertility control.

Patricia Geraghty is a women's health and family nurse practitioner at Muir Obstetric and Gynecologic Medical Group in Walnut Creek, Calif.

References

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