Life extension and
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Intermittent fasting and dieting and reproductive health.

The data from the Dutch famine study suggested that in uteroexposure to famine was not associated with subsequent subfer-tility, including age at first pregnancy, completed family size, andinter-pregnancy interval [38]. Another study showed that womenwho were exposed to Dutch famine in utero had more children,more twins, and were less likely to remain childless. The famine hada direct influence on menstruation patterns. Severe famine expo-sure was associated with increased risk of irregular menses. CR inchildhood was associated with a higher risk of prolonged time formenses to become regular after menarche [39].

CR has also been shown to reduce 
age at menopause. Women who were severely exposed to the famine during World War IIexperienced natural menopause on average 0.36 years earlier.This finding may have significant health implications since ear-lier age at menopause has been associated with increased risk of morbidity due to osteoporosis [40], cardiovascular disease [41],and cognitive decline [42].

It is particularly and perhaps alarm-ingly 
 problematic that higher burden of osteoporosis has been documented in some of the published studies. Bone is particularlysensitive to prolonged oligoovulation and resultant hypoestro-genism. The impact of such diet as IF on bone function may escapeeasy and reliable detection since the after effect of acute energyavailability may not be observed for decades. This is especially relevant for adolescents as adequate build-up of bone mass in womentakes place during the early reproductive years.The energy availability hypothesis has been proposed recently.It postulates that reproductive function in women is regulated notby the actual amount of body mass and body fat, but rather byavailable energy [43].

Experiments that imposed a high volume of aerobic exercise in an abrupt fashion caused a large prevalence 
ofanovulation in the first and second month after starting the exercise[44]. The period after bariatric surgery represents another example of potential low energy availability due to CR. A recent studyof 29 women undergoing bariatric surgery found that more than 90% of studied cycles were ovulatory [45]. In contrast, an earlierstudy reported that women in the rapid phase of weight loss afterbariatric surgery exhibit transient anovulation [46], presumablydue to low energy availability.


[38] Lumey LH. Reproductive outcomes in women prenatally exposed to undernu-trition: a review of findings from the Dutch famine birth cohort. Proc Nutr Soc1998;57(1):129–35.

[39] Elias SG, et al. Menstruation during and after caloric restriction: the 1944–1945Dutch famine. Fertil Steril 2007;88(4 Suppl):1101–7.

[40] Sowers MR, La Pietra MT. Menopause: its epidemiology and potential associa-tion with chronic diseases. Epidemiol Rev 1995;17(2):287–302.

[41] van der Schouw YT, et al. Age at menopause as a risk factor for cardiovascularmortality. Lancet 1996;347(9003):714–8.

[42] Wise PM, et al. Minireview: neuroprotective effects of estrogen-new insightsinto mechanisms of action. Endocrinology 2001;142(3):969–73.

[43] Loucks AB. Energy availability: not body fatness, regulates reproductive func-tion in women. Exerc Sport Sci Rev 2003;31(3):144–8.

[44] Bullen BA, et al. Induction of menstrual disorders by strenuous exercise inuntrained women. N Engl J Med 1985;312(21):1349–53.

[45] Legro RS, et al. Effects of gastric bypass surgery on female reproductive function.J Clin Endocrinol Metab 2012;97(12):4540–8.

[46] Di Carlo C, et al. Hypogonadotropic hypogonadism in obese women after bil-iopancreatic diversion. Fertil Steril 1999;72(5):905–9.

A case of obesity, diabetes and hypertension treated with very low calorie diet (VLCD) followed by successful pregnancy with intrauterine insemination (IUI).
Endocr J 2000 Dec;47(6):787-91.
Katsuki A, Sumida Y, Ito K, Murashima S, Gabazza EC, Furuta M, Yano Y, Sugiyama T, Toyoda N, Adachi Y. 
Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.

The patient was a 32-year-old obese woman with a history of type 2 diabetes and hypertension for 6 years. Although she was treated with antihypertensive agents and intensive insulin therapy, her hyperglycemia was difficult to control. She wanted to have a baby but pregnancy was not recommended because her diabetes was under poor control and the use of antihypertensive medication. To achieve good control of obesity, diabetes and hypertension, she was admitted to our clinical department for weight reduction using very low calorie diet (VLCD). During VLCD she had a 19.8 kg reduction in body weight and her blood glucose and blood pressure were in good control without the use of drugs. Five months later, she became pregnant after the fourth trial of intrauterine insemination (IUI) and gave birth to a female baby under insulin therapy. This is the first report that showed the usefulness of VLCD for prepregnant control of glucose metabolism and blood pressure in an obese hypertensive patient with type 2 diabetes mellitus.

Rejuvenating effects of 10-week underfeeding period on estrous cycles in young and old rats.
Neurobiol Aging 1987 May-Jun;8(3):225-32. 
Quigley K; Goya R; Meites J.

The effects of providing 50% of normal feed intake for 10 weeks followed by 16 weeks of ad lib feeding on estrous cycles and mammary tumor incidence were studied in female rats initially 4 months and 15-16 months old. Initially all young rats exhibited regular or irregular estrous cycles and only about 41% of the older rats cycled regularly or irregularly; the remainder of the older rats did not cycle. During underfeeding, both the young and older rats lost body weight and ceased to cycle. After refeeding 100% of both young and old rats resumed cycling, the young rats for a much longer period than the old rats, and more of both groups continued to cycle than their ad lib-fed controls. Upon refeeding, the young and old rats reached the body weights of the ad lib-fed controls in about 3 weeks. Mammary tumors were initially present only in old rats and regressed during underfeeding; they rapidly reached control size upon refeeding. Plasma PRL levels declined during underfeeding but rebounded to higher than control values upon refeeding in both young and old rats. In young but not in old rats, plasma LH levels fell during underfeeding but returned to control values upon refeeding. These results demonstrate that a relatively short period of underfeeding, followed by refeeding, can delay the decline in reproductive cycles in young rats and reinitiate estrous cycles in older rats. These effects appear to be mediated via the neuroendocrine system.

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