Non-polymeric microspheres are stable-shaped particles constituted by crystalline organic compounds. This technology allows controlled release of parental products that has its prime value on estrogen therapy. The structure is a nonpolymeric crystalline microsphere that uses a low solubility fatty acid, cholesterol as a carrier. Cholesterol is a waxy lipid, a substance that is insoluble in water and has been recognized as safe as excipient by FDA for the manufacturing of drugs. Cholesterol is a lipid present in the cell membrane and subcellular organelles of tissues and serves as the building block for all steroid hormones including cortisol, aldosterone, estrogen, and testosterone; therefore, this fatty acid provides better biocompatibility than polymers. The use of cholesterol as a low solubility carrier was used to develop a first of its kind, parental HT product for the management of menopausal symptoms carrying estrogen microspheres in an aqueous suspension, which would allow an extended estrogen release maintaining plasmatic therapeutic concentrations. Estradiol doses would be up to 30 times lower than that provided by oral and transdermal routes fulfilling current recommendations regarding the use of a low dose and the nonoral route. Both intramuscular monthly administered formulations of E/P non-polymeric microspheres had favorable pharmacokinetic and safety profiles, suggesting this route as an interesting, novel, and suitable way of treating menopause-related symptoms.