Experience with oral contraceptives

The Indian Contraceptive Testing Unit started making field trials with oral contraceptives in 1964. By June 1968, 958 women were taking oral contraceptives. Combination tablets used contained a minimum amount of progestogen (.5-3 mg) and a suitable amount of estrogen. The 21-tablet pack was found mot suitable. It was found that if a woman missed taking the tablets in the latter half of the cycle usually no harm resulted, but if she missed them at the beginning of the cycle pregnancy might follow as ovulation would not be inhibited. Main contraindications are liver damage, toxic hyperthyroidism, thromboembolic disease, and cancer of the genital tract or breast. Caution is advised for persons with chronic nephritis, a history of eclampsia, hypertension, varicose veins, ophthalmological disorders, or psychic depressive states. Side effects have been less with the smaller doses. The most serious side effect is thromboembolism. Those reported have been leg pain, giddiness, headache, breakthrough bleeding, nausea, vomiting, amenorrhea, abdominal pain, weakness, increased blood pressure, and skin rashes. Others have reported ocular disease and cranial nerve palsy. Sequential therapy has been reported to have a lower incidence of side effects but a higher rate of pregnancy. Low-dose progestogen therapy, the "minipill," does not inhibit ovulation but is effective by causing changes in the endometrium and in the mucus. The chlormadinone in the minipill does not affect lactation. However, the incidence of pregnancy is similar to that with an IUD (Lippes loop) which is 2.6/100 cases. Laboratory tests have been normal, except an increase in the thymol turbidity test. Vaginal cytology has revealed no case of malignancy. Results show that oral contraceptives are suitable for use on a mass scale as a method of population control.     

Ibandronate: the evolution of a once-a-month oral therapy for postmenopausal osteoporosis.

Bisphosphonates have been shown to be highly effective in preventing and treating postmenopausal osteoporosis (PMO) and the associated risk of fracture. However, poor adherence with bisphosphonate therapies for PMO results in a high incidence of otherwise preventable fractures. The chronicity of this condition requires long-term treatment, but fewer than one in two women remains on daily bisphosphonate therapy for 1 yr. A good way to reduce the risk of osteoporotic fractures is through development of equally efficacious formulations with more convenient dosing regimens. Weekly formulations of bisphosphonates have been introduced that demonstrate comparable efficacy to daily formulations with slightly improved adherence. Recently, a new formulation utilizing a third-generation nitrogen-containing bisphosphonate--ibandronate--has been approved with a monthly dosing regimen. The pharmacokinetics and high potency of ibandronate, similar with other bisphosphonates, facilitate lower mg doses and longer-interval dosing frequencies with similar efficacy and enhanced tolerability. Preclinical studies and clinical trials have consistently demonstrated that it is the total cumulative dose of ibandronate that determines efficacy. The convenience of once-monthly dosing may ultimately improve adherence and clinical outcomes among the growing population of postmenopausal women at risk of osteoporosis.     

Analysis of "drop-outs" in oral contraceptives

This article emphasizes the authors' experience with a rural family planning program. Most acceptors were of low economic status and mostly illiterate. A negligible number had previous experience with contraception. After a clinical examination, 373 women were each given a monthly supply of Ovulen. Field workers paid regular follow-up visits to encourage regularity in taking the pills and to note side effects. 133(32%) stopped taking the pills. Of those under age 20 years, 87% dropped out; of those 21-25 years, 30% dropped out; of those 26 or older, 25% discontinued. 65% of women with 1 child stopped; 50% of those with 2-4 discontinued; 35% of women with 6 or more children stopped. Of the 133 "drop-outs," 49 had complaints related to medication and 30 discontinued for these reasons. In 15 instances patients were lost to follow-up. 17 discontinued because of husbands' objections. No religious reasons were given. Some elders in the villages objected. In 20 instances planned pregnancies were desired and in 19 pregnancy occurred as a result of irregular pill use. Other reasons were sterilization or marital break-up. More than 60% of those who discontinued for medical reasons did so after the 1st cycle. It was found that 239 of the women were lactating. There were no drop-outs due to scanty lactation. Results of the survey are considered encouraging. The women were not as adverse to taking pills as they were to physical trauma such as tuvectomy or IUD insertion. The method should be promoted. Free distribution of pills is recommended as the people were very poor.     

Aorto-iliac occlusion in women using oral contraceptives. A report of 2 cases

2 case reports of ischamic symptoms from aorto-iliac occlusion in premenopausal women (ages 29 and 44 years) which began during medication with oral contraceptives suggest that oral contraceptives may be dangerous to patients with a latent tendency to arterial disease and that such patients can be identified before complications arise.     

Hepatocellular carcinoma associated with oral contraceptives.

A primary hepatic tumour occurred in a 36-year-old woman who had been taking oral contraceptives for 6 years; she was treated by partial hepatectomy. The neoplasm had the characteristics of a well-differentiated hepatocellular carcinoma and the regional lymph nodes contained similar tumour.     

Mesenteric venous thrombosis in two women taking oral contraceptives

2 cases of mesenteric venous thrombosis in women taking oral contraceptives (48-year old gravida 5 taking norethindrone with mestranol for 10 years, a 33-year old gravida 2 taking Enovid and C-Quens since 1962 followed by norethindrone with mestranol 1 month prior to admission) were treated at the Jewish Hospital of St. Louis. Both patients had acute abdominal pain, vomiting, and bloody and diarrheal stools. In order to remove nonviable portions of the bowel which are viable at initail operation, 2 operations are necessary in the treatment of mesenteric venous thrombosis. Both of these patients underwent 2 operations and both had extensive segments of bowel removed. The post-operative courses of both patients were long (85 and 40 days respectively) and difficult. No predisposing or etiologic factor could be determined in either patient. A relationship of mesenteric venous thrombosis to oral contraceptives is suggested, but no definite causal relationship can be established.     

复方口服避孕药中孕激素的多晶型研究进展

口服避孕药上市后已经成为世界上最普遍的避孕方法之一。复方口服避孕药(COC)由雌激素和孕激素组成,其作用机理的差别主要由所含孕激素决定的。口服孕激素存在多晶型现象,不同的晶型可通过影响其理化性质、生物利用度而导致药物的药效和安全性产生差异。本文对口服避孕药中孕激素的多晶型研究现状进行综述,为药物的生产和质控提供参考,进而保障用药安全、有效,提高避孕节育效率。     

Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report

A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.     

Hepatic adenoma and oral contraceptives (author's transl)

The authors report a new case of hepatic adenoma apparently related to oral contraception continued for more than 9 years with a pill containing mestranol. The clinical presentation suggested an attack of hepatic colic with swollen gall bladder. The preoperative diagnosis of a tumour of segment VI of the liver was made by radiological examination of neighbouring organs. Hepatic arteriography, hepatic radioisotope scan using technetium phytate and echotomography. Surgical removal of segment VI confirmed by histological study showed that it was an adenoma with multiple foci, associated with hepatic involvement. One of the tumours was the site of central included hemorrhage, responsible for the clinical syndrome. In connection with this case the authors review the possible relationship between hepatic adenoma and oral contraception.     

Cerebral venous thrombosis associated with the use of oral contraceptives

The entity of cerebrovascular diseases associated with the use of oral contraceptives is well known but quite rare in Japan in contrast to Western countries. We recently encountered a 38 years old female with cerebral venous thrombosis considered to be caused by oral contraception. This patient took oral contraceptives for 17 days following therapeutic abortion, and was transferred to our hospital because of disturbed consciousness. CT scans disclosed a right temporo-occipital subcortical hemorrhagic infarction and bilateral thalamic infarction. Cerebral angiograms showed non-filling of cortical veins in the same area. The internal cerebral vein, vein of Galen and right transverse sinus were not visualized either. The hematoma and necrotic tissue were removed to avoid farther neurological deterioration. The brain was swollen and hyperemic, and thrombosed cortical veins were clearly recognized at operation. Twelve cases, including ours, of cerebrovascular diseases associated with oral contraception were reported up to now in Japan, and only 3 of them were diagnosed objectively as venous or sinus thrombosis. The average age of these 12 cases was 34 years old and many of them experienced abortion or therapeutic abortion. There was no relationship between the dose of estrogen and the onset of cerebrovascular diseases. We believe that the onset of this pathological state is based on gynecological hypercoagulable state, and the oral contraception may play a role of a trigger. Oral contraception should be contraindicated in patients with gynecological hypercoagulable state, hypertension and/or smoking habit.