Copyright © 2008 Massachusetts Medical Society. A 58-year-old man is found on laboratory testing to have a serum calcium level of 6.0 mg per deciliter (1.5 mmol per liter) (normal range, 8.5 to 10.5 mg per deciliter [2.1 to 2.6 mmol per liter]), an albumin level of 3.9 g per deciliter, and a phosphorus level of 6.0 mg per deciliter (1.94 mmol per liter) (normal range, 2.5 to 4.5 mg per deciliter [0.81 to 1.45 mmol per liter]). His medical history is notable only for longstanding hearing difficulties. He reports no history of neck surgery and no throat tightness, muscle cramps, paresthesias, or seizures. His father and sister, who are both deceased, had kidney disease. On physical examination, both Chvostek’s and Trousseau’s signs are negative. His ionized calcium level is 0.75 mmol per liter (normal range, 1.10 to 1.32). How should his case be further evaluated and treated?

Clinical practice. Hypoparathyroidism.

Background
The avoidance of menstruation through continuous or extended (greater than 28 days) administration of combination hormonal contraceptives (CHCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through extended or continuous use of CHCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school.

Objectives
To determine the differences between continuous or extended-cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active hormone compared with traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormones and 4 days of placebo). Our hypothesis was that continuous or extended-cycle CHCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with standard cyclic CHCs.

Search methods
We searched computerized databases (Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, POPLINE, LILACS) for trials using continuous or extended CHCs (oral contraceptives, contraceptive ring and patch) during the years 1966 to 2013. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references.

Selection criteria
All randomized controlled trials in any language comparing continuous or extended-cycle (greater than 28 days of active hormones) versus traditional cyclic administration (21 days of active hormones and 7 days of placebo, or 24 days of active hormones and 4 days of placebo) of CHCs for contraception.

Data collection and analysis
Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 5. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow-up, and early discontinuation. Because the included trials did not have a standard treatment (type of CHC formulation, route of delivery, or time length for continuous dosing), we could not aggregate data into meta-analysis.

Main results
Twelve randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended or continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended or continuous cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group. The studies that reported menstrual symptoms found that the extended or continuous group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven out of the twelve studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles over time. Endometrial lining assessments by ultrasound and/or endometrial biopsy were done in some participants and were all normal after cyclic or extended CHC use.

Authors' conclusions
The 2014 update yielded four additional trials but unchanged conclusions. Evidence from existing randomized control trials comparing continuous or extended-cycle CHCs (greater than 28 days of active combined hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormone and 4 days of placebo) is of good quality. However, the variations in type of hormones and time length for extended-cycle dosing make a formal meta-analysis impossible. Future studies should choose a previously described type of CHC and dosing regimen. More attention needs to be directed towards participant satisfaction, continuation, and menstruation-associated symptoms.

Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception

https://www.endo.theclinics.com/article/S0889-8529(11)00067-3/pdf

Calcium and Bone Metabolism Disorders During Pregnancy and Lactation

https://www.endo.theclinics.com/article/S0889-8529(05)00114-3/pdf

Calcium and bone disorders during pregnancy and lactation.

Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the 'real-life' efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy.

http://taw.sagepub.com/content/5/5/201.full.pdf

Stephanie L. Koontz

Papers

Continuous oral contraceptives: are bleeding patterns dependent on the hormones given?

Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine.

Treating incomplete abortion in El Salvador: cost savings with manual vacuum aspiration.

Cost savings of manual vacuum aspiration for endometrial sampling in El Salvador