Oligomenorrhea; causes, symptoms and treatment

OLIGOMENORRHEA

The most prevalent cause of oligomenorrhea is PCOS, a heterogeneous disorder that is present in 6–10% of women of reproductive age. Low-dose OCs containing 30 μg or less of ethinlyestradiol in combination with a thirdgeneration progestin should be the treatment of choice in non-smoking patients with PCOS who desire contraception, and who do not have any risk factors for venous thromboembolism. In addition to providing adequate contraception and endometrial protection, this combination is effective in suppression of circulating androgen levels. Used alone, low-dose OCs are effective in controlling mild hirsutism which is the most frequent hyperandrogenic manifestation of the syndrome. In part, this effect is secondary to increased hepatic sex hormone binding globulin (SHBG) production resulting in lower free circulating testosterone levels . Additionally, the progestogen in the COC can lead to an antagonism of 5α-reductase and the androgen receptor, and a further decrease in SHBG concentrations. It is advisable to select an OC containing a progestin with low androgenic activity. Predictable withdrawal bleeding in response to oral contraceptive treatment is reassuring evidence against the development of endometrial hyperplasia, rendering frequent endometrial assessments unnecessary. The LNG-IUS may also be used to obviate the effect of unopposed estrogen on the endometrium. Limited data from small case series suggest that this may be an excellent treatment for endometrial hyperplasia; however, corroboratory evidence from results of long-term studies is lacking. A concern regarding possible insulin desensitizing effects of oral contraceptives has been raised. Although older, higherdose oral contraceptives worsen insulin sensitivity, longterm follow-up studies have failed to detect any increase in the incidence of diabetes mellitus in past or current users of high-dose pills. Furthermore, the effect of the OC on insulin metabolism appears to be dose related, thus it is advisable to use the newer generation of lowdose contraceptive preparations. These preparations containing ethinylestradiol 30μg or less and desogestrel, norgestimate, or gestodene as the progestin component do not appear to worsen lipid and lipoprotein profile or adversely affect the surrogate biochemical markers of cardiovascular disease. Neither do they appear to have a deleterious effect on insulin sensitivity in women with PCOS.

Oligomenorrhea

 

Cyproterone acetate in conjunction with ethinlyestradiol is superior to the combined estrogen progestin pill alone in the management of the hyperandrogenic manifestations of the disorder, particularly hirsutism. Cyproterone acetate is a 17- hydroxyprogesterone acetate derivative with strong progestogenic properties. The drug mainly acts as an anti-androgen by competing with dihydrotestosterone (DHT) and testosterone for binding to the androgen receptor. There is also some evidence that cyproterone acetate and ethinylestradiol in combination can inhibit 5α-reductase activity in the skin. Treatment in a reverse sequential manner (using 50 mg of cyproterone in the early follicular phase of the cycle, with the addition of ethinlyestradiol 50 μg from day 5 to 25) is now seldom used. Smaller doses (2mg) in daily combination with 35μg of ethinylestradiol (Dianette®, Schering Health Care, West Sussex, UK) administered daily is a popular contraceptive preparation hirsutism. However, disturbingly, a four-fold higher risk of venous thromboembolism (VTE) is associated with its use compared with levonorgestrel in a large case—control study. Other studies however, have not been able to confirm this association.

Clearly more studies are needed to clarify the association between cyproterone acetate and VTE. Pending better elaboration of its safety profile, cyproterone should be used after due counseling and after considering the potential benefits of this treatment. More severe forms of hirsutism may warrant alternative strategies.

MENORRHAGIA

Menorrhagia is defined as blood loss greater than 80ml per cycle and/or menstrual periods or a complaint of regular excessive menstrual bleeding over several consecutive cycles.The complaint accounts for 12% of all gynecological referrals for menstrual dysfunction to gynecologists in the UK.

Combined contraceptives

Contraceptive preparations are often tried as first-line treatments, and various delivery systems are available. These include oral, transdermal and vaginal routes.

Combined oral contraceptives

COCs are frequently used in the primary management of menorrhagia especially when contraception is needed. COCs, may act by several mechanisms to decrease the menstrual blood loss (MBL). They act primarily by suppressing the estrogen-induced mid-cycle surge of gonadotropin secretion, and thus inhibition of ovulation. Combination of regular shedding of the thin endometrium and anovulation results in endometrial atrophy. In the absence of contraindications, pills containing at least 30 μg of ethinylestradiol should be prescribed. Although clinically the combined COC is an effective treatment for menorrhagia, most studies on its use are limited by methodological shortcomings and inadequate patient numbers, as well as by the dissimilar dose of ethinylestradiol employed in the various studies. Notwithstanding these inadequacies, evidence from these controlled observational studies, and meta-analysis  points to a modest, but significant benefit of the COC in reducing menstrual blood loss compared to baseline measurements. This benefit appears to be greater in studies that have employed higher dose of estrogen than the 30–35 mg of preparations currently in use. The effectiveness of lower-dose pills in reducing MBL is unclear. Indeed, lowerdose combination pills may paradoxically cause irregular uterine bleeding. It has been suggested that the perturbations in menstrual cyclicity with these preparations may be countered by altering the progestin dosage. It is unclear whether changing the progestin type has an appreciable beneficial effect on the MBL in patients with menorrhagia.

Clearly the simplicity of treatment, familiarity with its usage, and the appreciation of the non-contraceptive benefits of the pill ensure a place for the COC in the primary management of menorrhagia in women desiring contraception. The non-contraceptive benefits of the COC, include reduction in dysmenorrhea, and reduction in the incidence of ovarian and endometrial cancers. The absolute contraindications for estrogen use are previous VTE event or stroke, history of an estrogen-dependent tumor, and liver disease. Undiagnosed abnormal uterine bleeding, hypertriglyceridemia, and women over age 35 years who smoke should also be regarded as contraindications to its use. Although pregnancy should be regarded as an absolute contraindication, inadvertent COC use during early pregnancy has not been associated with an increase in risk of congenital anomalies with the possible exception of congenital urinary tract abnormalities. Caution should be exercised in using COCs in women with poorly controlled hypertension, those on anticonvulsant therapy, and women with migraine, particularly those with associated focal neurological symptoms, who may be at increased risk of stroke cerebrovascular incident.

Non-oral routes of administration

Non-oral routes have the advantage of better patient compliance and equal contraceptive effectiveness. For example, the transdermal contraceptive patch (Ortho Evra®, Ortho-Mcneil, Raritan, NJ, USA), which delivers 20μg of ethinylestradiol and 150μg of norelgestromin daily, and the contraceptive ring (NuvaRing®, Organon, Roseland, NJ, USA), which delivers 15μg ethinylestradiol and 120μg of etonogestrel daily intravaginally, offer highly effective contraception with few side-effects. However, given the paucity of long-term studies, it is not possible to comment on their effectiveness as viable therapeutic agents in the management of women with abnormal menstrual rhythm. Pending further elucidation of its role in the symptomatic management of menorrhagia, and despite the higher incidence of irregular bleeding with these preparations, the userfriendly mode of non-oral administrations ensures excellent patient compliance and satisfaction compared with the COC, and has a lower rate of discontinuation.Thus, despite the shortcomings, these preparations may be a method of choice in women who also desire contraception.

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