<p>Intraperitoneal LD50 (rat): 327 mg/kg <sup class="text-reference-group"><a class="reference-popover-link" data-content="Material Safety Data Sheet" href="#msds-reference">MSDS</a></sup>. </p><p><strong>Use in pregnancy</strong></p><p>Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy <sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup>, <sup class="text-reference-group"><a class="reference-popover-link" data-content="Norethindrone FDA label" href="#reference-F3904">22</a></sup>. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive <sup class="text-reference-group"><a class="reference-popover-link" data-content="Norethindrone FDA label" href="#reference-F3904">22</a></sup>. </p><p><strong>Effects on fertility</strong></p><p>Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation <sup class="text-reference-group"><a class="reference-popover-link" data-content="PROGESTERONE INJECTION USP IN SESAME OIL FOR INTRAMUSCULAR USE ONLY" href="#reference-F3916">25</a></sup>. The progesterone contraceptive should not be used during pregnancy. </p><p><strong>Carcinogenicity</strong></p><p>Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown <sup class="text-reference-group"><a class="reference-popover-link" data-content="Utrogestan capsules, medsafe NZ label" href="#reference-F3913">24</a></sup>. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use <sup class="text-reference-group"><a class="reference-popover-link" data-content="Norethindrone FDA label" href="#reference-F3904">22</a></sup>. </p><p><strong>Use in breastfeeding</strong></p><p>Progesterone has been detected in the milk of nursing mothers <sup class="text-reference-group"><a class="reference-popover-link" data-content="Endometrin FDA label, vaginal insert" href="#reference-F3901">21</a></sup>, <sup class="text-reference-group"><a class="reference-popover-link" data-content="Norethindrone FDA label" href="#reference-F3904">22</a></sup>. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported <sup class="text-reference-group"><a class="reference-popover-link" data-content="Norethindrone FDA label" href="#reference-F3904">22</a></sup>. </p>